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44 Study Matches
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT06238479
STU-2024-0162
Inclusion Criteria:
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event or bleeding disorder
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention DRUG: LY4101174
Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-Small Cell Lung Cancer, Esophageal Cancer, Pancreatic Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Prostate Cancer, Renal Pelvis Cancer, Bladder Cancer, Breast - Female, Breast - Male, Cervix, Esophagus, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Ovary, Pancreas, Prostate, Urinary Bladder
Bladder Cancer, Bladder Neoplasm, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Urothelial Neoplasms, Renal Pelvis Cancer, Ureter Cancer, Nectin-4, Antibody Drug Conjugate (ADC)
UT Southwestern
National Liver Cancer Screening Trial (TRACER)
The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Amit Singal
ALL
18 Years to 85 Years old
PHASE4
NCT06084234
STU-2023-0842
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
• Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
• Patient is eligible for HCC surveillance according to treating physician or by the site investigator
• Able to provide informed consent
• Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
• Child Pugh C cirrhosis
• History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
• History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
• AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
• Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
• History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
• Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
• Patient's provider is planning to use MRI- or CT- based surveillance moving forward
• History of a transjugular intrahepatic portosystemic shunt (TIPS)
• History of Fontan associated liver disease or cardiac cirrhosis
• History of solid organ transplantation
• Actively listed for liver transplantation
• Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
• Known pregnancy at consent
• Active warfarin use
DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP
Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B, Liver
Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein
UT Southwestern; Parkland Health & Hospital System
A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination with Cemiplimab in Patients with Advanced Solid Tumors and Lymphomas. (ON-5001)
A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years and over
PHASE1
NCT06022029
STU-2023-0921
Inclusion Criteria:
• Ability to understand and willingness to sign written informed consent before performance of any study procedures
• Age ≥ 18 years
• Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
• Participants must have a minimum of one injectable and measurable lesion.
• Participants with prior Hepatitis B or C are eligible if they have adequate liver function
• Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load \<400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• Adequate bone marrow function:
• Adequate liver function
Exclusion Criteria:
Patients will be excluded from this study if they meet any of the following criteria (Part 1a and Part 1b).
• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
• Major surgery within 4 weeks before the first dose of study drug.
• Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
• Prolongation of corrected QT (QTc) interval to \>470 millisecond (ms) for males and females when electrolytes balance is normal.
• Females who are breastfeeding or pregnant at screening or baseline
• Females of childbearing potential that refuse to use a highly effective method of contraception.
• Has uncontrolled or poorly controlled hypertension as defined by a sustained BP \> 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
• Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
• Has known hypersensitivity to any component in the formulation of cemiplimab
• Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily prednisone equivalent)
• Has a condition requiring systemic treatment with corticosteroids
DRUG: ONM-501, DRUG: Cemiplimab
Triple Negative Breast Cancer, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Bladder Cancer, Uveal Melanoma, Recurrent, Cervix Cancer, Carcinoma In Situ, Head and Neck Squamous Cell Carcinoma, Skin Cancer, Metastatic Cancer, Tumor, Solid, Tumor Recurrence, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Lung/Thoracic, Lymphoid Leukemia, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder
Solid tumors, Lymphoma, ONM-501, STING, Intra-tumoral, HNSCC, Breast Cancer, Melanoma, Skin Cancer, cemiplimab, Libtayo, DLBCL, bladder cancer, cervical cancer, metastases, immunotherapy, ICI, TNBC, Triple Negative, mTNBC, anti-PD-1 antibody, BRCA1, BRCA2, anti-PD-L1, uveal, NHL, Mantle Zone lymphoma, FL, stimulator of interferon genes
UT Southwestern
A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years and over
PHASE1
NCT05908786
STU-2023-0659
Inclusion Criteria:
* Diagnosis of HCC confirmed either histologically or clinically according to AASLD criteria for patients with cirrhosis. For participants without cirrhosis, histological confirmation is mandatory.
* HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant. Patients presenting with resectable HCC within or beyond Milan criteria (without extrahepatic spread or macrovascular invasion) are eligible.
* Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
* Child-Pugh Class A within 7 days prior to randomization
* Negative HIV test at screening
* No prior locoregional or systemic treatment for HCC
* Adequate hematologic and end-organ function
* Documented virology status of hepatitis
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm
General Exclusion Criteria:
* Presence of extrahepatic disease or macrovascular invasion
* Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC
* History of hepatic encephalopathy if clinically significant within one year prior to initiation of study treatment
* Moderate or severe ascites
* Active co-infection with HBV and HCV
* Known active co-infection with HBV and hepatitis D viral infection
* Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Inadequately controlled hypertension
* History of hypertensive crisis or hypertensive encephalopathy
* Significant vascular disease within 6 months prior to initiation of study treatment
* History of hemoptysis within 1 month prior to initiation of study treatment
* Evidence of bleeding diathesis or significant coagulopathy
* Current or recent (\<= 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
* History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal abscesses within 6 months prior to initiation of study treatment
* History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction
* Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
* Grade \>= proteinuria
* Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal surgery, interventions or traumatic injuries, or anticipation of need of major surgical procedure other than potentially curative liver resection
* Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
* Serious infection requiring oral or IV antibiotics and/or hospitalization
* Active tuberculosis DRUG: Atezolizumab, DRUG: Bevacizumab, DRUG: Tiragolumab, DRUG: Tobemstomig
Carcinoma, Hepatocellular, Liver
UT Southwestern; Parkland Health & Hospital System
A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors
The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
All
18 Years and over
Phase 1
NCT05892718
STU-2023-1031
Inclusion Criteria:
• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.
Exclusion Criteria:
• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.
Drug: HCB101
Advanced Solid Tumor, Refractory Non-Hodgkin Lymphoma, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Multiple Myeloma, Non-Hodgkins Lymphoma, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Stomach, Thyroid, Urinary Bladder
Immunotherapy, CD47, SIRPα, Solid Tumor, Lymphoma
UT Southwestern; Parkland Health & Hospital System
Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial
This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Cecilia Ethun
ALL
18 Years and over
PHASE3
NCT05863195
STU-2024-0075
Inclusion Criteria:
* Patient must be \>= 18 years of age
* Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
* Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).
* NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
* Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension.
* Patient's primary tumor may be in place.
* Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.
* NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
* Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
* Patient must meet the following criteria for technical unresectability:
* A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
* NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
* Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization)
* Calcium \>= institutional lower limit of normal (LLN)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study
Exclusion Criteria:
* Patient must not have a liver tumor burden exceeding 70% of total liver volume.
* Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization).
* Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
* Patient must not have had prior treatment with HAI/floxuridine (FUDR)
* Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
* Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
* Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
* Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial.
* Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. BIOLOGICAL: Bevacizumab, BIOLOGICAL: Cetuximab, PROCEDURE: Computed Tomography, DRUG: Floxuridine, DRUG: Fluorouracil, PROCEDURE: Implantation, PROCEDURE: Intrahepatic Infusion Procedure, DRUG: Irinotecan, DRUG: Leucovorin, DRUG: Oxaliplatin, BIOLOGICAL: Panitumumab, PROCEDURE: Single Photon Emission Computed Tomography
Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma, Colon, Liver, Rectum
UT Southwestern; Parkland Health & Hospital System
A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
ALL
180 Days to 22 Years old
PHASE2
NCT05828069
STU-2023-0818
Inclusion Criteria:
* 180 days- \< 22 years (at time of study enrollment)
* Patient must have a body surface area of ≥ 0.3 m\^2
* Patients with progressive, relapsed, or recurrent LCH with measurable disease at study entry
* Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
* Tissue confirmation of relapse is recommended but not required
* Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
* Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
* Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
* Patients must have measurable disease, documented by radiographic imaging (LCH- specific response criteria (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary).
* Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy
* Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
* Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50% for patients =\< 16 years of age
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
* Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)
* Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
* Patients must have fully recovered from any prior surgery
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Steroids: =\< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible
* Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
* Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
* Peripheral absolute neutrophil count (ANC) \>= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Platelet count \>= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Patients with marrow disease must have platelet count of \>= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
* Hemoglobin \>= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin \>= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
* Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta \[registered trademark\]) or 7 days for short-acting growth factor
* A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Age: 6 months to \< 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
* Age: 1 to \< 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
* Age: 2 to \< 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
* Age: 6 to \< 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
* Age: 10 to \< 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
* 13 to \< 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
* Age: \>= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
* OR- a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2
* OR- a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Alanine aminotransferase (ALT) =\< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum albumin \>= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
* Fractional shortening (FS) of \>= 25% or ejection fraction of \>= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
* Central Nervous System Function Defined As:
* Patients with seizure disorder may be enrolled if well controlled
* Central nervous system (CNS) toxicity =\< Grade 2
* Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
Exclusion Criteria:
* LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy
* Disease scenarios as below will be excluded
* Skin-limited disease
* Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
* LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
* Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
* Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
* Uncontrolled systemic bacterial, viral, or fungal infection
* Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
* History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
* Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
* History of solid organ or hematopoietic bone marrow transplantation
* Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval \> 440 ms based on triplicate electrocardiogram (ECG) average
* History of Grade \>= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
* History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
* CTCAE version (V). 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation ( \> 5 x ULN)
* Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are ineligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Participants (male and female) who are sexually active must use two forms of an acceptable method of birth control (for men, one form must be a barrier method) from start of therapy through 180 days following last dose of tovorafenib (DAY101) PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, PROCEDURE: FDG-Positron Emission Tomography and Computed Tomography Scan, PROCEDURE: Lumbar Puncture, PROCEDURE: Multigated Acquisition Scan, DRUG: Tovorafenib
Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis, Bones and Joints, Other Skin, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic, Small Intestine
Children’s Health
Study of JANX008 in Subjects with Advanced or Metastatic Solid Tumor Malignancies
This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to 100 Years old
PHASE1
NCT05783622
STU-2023-0808
Inclusion Criteria:
* Subjects ≥18 years of age at the time of signing informed consent
* Histologically or cytologically documented locally advanced or metastatic NSCLC, SCCHN, CRC, RCC, SCLC, PDAC, TNBC
* Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for the tumor type
* Adequate organ function
* At least 1 measurable lesion per RECIST 1.1
Exclusion Criteria:
* Treatment with anti-cancer therapy within 28 days or ≤5 elimination half-lives, whichever is earlier, before enrollment
* Prior treatment with EGFR-targeted bispecific T cell engager or CAR-T cell therapy
* Prior treatment with CD3 engaging bispecific antibodies
* Clinically significant cardiovascular diseases
* Active clinically significant infection (bacterial, viral, fungal, mycobacteria, or other)
* On supplemental oxygen
* Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment DRUG: JANX008
Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck, Colorectal Carcinoma, Small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Triple-Negative Breast Cancer, Colon, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Rectum
UT Southwestern
A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma
This study will be conducted in 2 parts. The first part is a phase 1 single-agent dose escalation,optimization, and expansion study of tegavivint in patients with advanced HCC after failure of at least one line of prior systemic therapy. In the second part of the study, the combination of tegavivint plus pembrolizumab will be assessed with a limited dose escalation followed by a randomized dose optimization.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years and over
PHASE1
NCT05797805
STU-2023-0867
Inclusion Criteria:
* Male or female, 18 years of age or older
* Confirmed diagnosis of HCC by either:
Histologically or cytologically documented HCC based on pathology report or Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria
* Presence of AXIN1 or CTNNB1 mutation is required for all patients, except those enrolled in the single agent dose escalation Documentation of comprehensive genomic profiling to assess for mutations in β-catenin signaling including AXIN1 and CTNNB1 is required for all patients
* Ascertainment from fresh biopsy or liquid biopsy during screening is allowed.
* Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
* Child-Pugh class A or ≤ 7 class B liver score (no hepatic encephalopathy) within 7 days of first dose of the investigational product(s)
* Disease progression, intolerance or contraindication to at least one line of systemic therapy for advanced HCC Prior treatment with a PD-1/PD-L1 inhibitor for at least one administration
* Measurable disease as defined by RECIST 1.1
* Willingness and ability to provide tumor biopsies during screening and while on treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of the investigational product(s)
* Patients must have organ and marrow function as defined below within 7 days of the first dose of the investigational product(s):
* Absolute neutrophil count (ANC) ≥ 1.2 x 109/L
* Platelets ≥ 60 x 109/L; no transfusion within 7 days prior to assessment
* Hemoglobin ≥ 9 g/dL (red blood cell transfusion or growth factors support is not allowed in the 14 days prior to the screening laboratory assessment)
* Total bilirubin ≤ 2 mg/dL, or direct bilirubin ≤ upper limit of normal (ULN) for those with total bilirubin \>2 mg/dL
* AST and ALT ≤ 5 x ULN
* Estimated creatinine clearance (CrCl) by the Cockcroft-Gault equation or measured ≥ 60 mL/min.
* Albumin ≥ 3.0 g/dL
* International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
* Washout period prior to Day 1 of Cycle 1:
* At least 21 days from the last dose of prior systemic anticancer treatment
* At least 14 days from palliative radiotherapy (≤ 10 fractions or ≤30 gray \[Gy\] total dose or at least 28 days from radiotherapy \> 30 Gy)
* Grade ≤ 1 toxicity due to any previous cancer therapy according to the NCI-CTCAE, v.5.
* Grade 2 is allowed in case of alopecia and/or peripheral sensory neuropathy.
* Participants with past HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention and HCV viral load must be below the limit of quantification.
* Participants with controlled HBV will be eligible if they meet the following criteria:
* Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of study drug. Patients on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention.
* Patients who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis.
* Patients must have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
Exclusion Criteria:
* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
* Patients receiving therapy with other anti-neoplastic or experimental agents
* Patients receiving concomitant strong inhibitors of CYP3A4/5 that cannot be discontinued 7 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
* Patients receiving concomitant inducers of CYP3A4/5 that cannot be discontinued at least 14 days prior to Cycle 1 Day 1.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint, or other agents used in study
* Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy.
* Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
* Known central nervous system (CNS) involvement
* Uncontrolled concurrent illness including, but not limited to:
* Ongoing or active infection (exception: HBV infection - see inclusion criteria)
* Unhealed wounds or presence of any external drainage
* Psychiatric illness/social situations that would limit compliance with study requirements; discuss with Medical Monitor if there are any questions
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
* Congestive heart failure, NYHA \> Class II
* Left ventricular ejection fraction \< 50%
* Unstable angina pectoris or cardiac arrhythmia
* Baseline QTc (Fridericia) ≥ 450 milliseconds. In the event a QTc (Fridericia) measurement is not possible due to factors such as a pacemaker or bundle branch block, the patient may be evaluated by a cardiologist who must document no apparent increased risk for Torsades de Point or other morbidity associated with prolonged QTc. With such documentation, the patient may be eligible based with additional Medical Monitor review.
* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
* Myocardial infarct within 6 months before Cycle 1 Day 1
* Clinically significant pericardial disease
* Any major surgery within 21 days prior to Cycle 1 Day 1. Major surgery is defined as any significantly invasive procedure into a major body cavity (abdomen, cranium etc.) and/or surgery requiring extensive recuperation (joint replacement). Please discuss with the Medical Monitor if there are any questions.
* Pregnant and breastfeeding women are excluded from this study. The effects of tegavivint on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tegavivint
* Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one highly effective method of contraception, including hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstaining from sex for the duration of study participation and for at least 4 months following completion of tegavivint and pembrolizumab (if applicable) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with tegavivint.
* Exclusions for patients treated on study with pembrolizumab:
* Have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
* Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
* Have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or have current pneumonitis/interstitial lung disease.
* Prior allogeneic organ or bone marrow transplant DRUG: Tegavivint, DRUG: Pembrolizumab
Advanced Hepatocellular Carcinoma, Liver
UT Southwestern; Parkland Health & Hospital System
Domvanalimab and Zimberelimab in Advanced Liver Cancers
The goal of this clinical trial is to learn about advanced liver and bile duct cancers. The main question it aims to answer is: If the combination of Domvanalimab and Zimberelimab are effective in treating advanced hepatobiliary cancers that have failed prior treatment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 2
NCT05724563
STU-2022-1076
Inclusion Criteria:
• Patient must have a histologically confirmed diagnosis consistent with HCC or bile duct cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers); known fibrolamellar HCC, or combined HCC-cholangiocarcinoma will be excluded.
• Locally advanced or metastatic disease
• 2a. Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• 2b. Measurable disease, as defined as lesions that can accurately be measured in at east one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Refractory to or relapsed after prior anti-PD-1/L1 antibody therapy. May have received anti-PD-1/L1 monotherapy or combination therapy as any line of therapy including in the neoadjuvant or adjuvant setting. Patients who discontinued prior immune checkpoint inhibitor treatment due to toxicity are not eligible.
• Availability of recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides in which the biopsy or resection was performed within 3 years. Baseline tissue can be obtained after consent but must be prior to initiation of zimberelimab and domvanalimab. It is strongly recommended that tissue is obtained from biopsies confirming progression of disease on prior therapy so that the patient has not received any intervening systemic anti-cancer treatment from the time that the baseline tissue was obtained.
• Prior locoregional is allowed provided the following are met: 1) at least 2 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation; 2) target lesion has increased in size ≥25% or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A or B7-8 (only for Cohort A)
• ECOG Performance score of 0-1
• Adequate organ and marrow function (without chronic, ongoing growth factor support or transfusion in the last 2 weeks) as defined below:
• 9a. Platelet count ≥ 50,000/mm^3
• 9b. Hgb ≥ 8.5 g/dl
• 9c. Absolute neutrophil ≥ 1,000 cells/mm^3
• 9d. Total bilirubin ≤ 3.0 mg/ml (This will not apply to subjects with Gilbert's syndrome who have persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis, and such patients may be enrolled based in consultation with the principal investigator).
• 9e. INR ≤ 2
• 9f. AST, ALT ≤5 times ULN
• 9g. Calculated creatinine clearance (CrCl) ≥ 40 mL/min. CrCl can be calculated using the Cockroft-Gault method.
• 9h. Albumin ≥ 2.0 g/dl
• All men, as well as women of child-bearing potential, defined as not surgically sterilized and between menarche and 1-year post menopause, must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 4 weeks prior to study entry, for the duration of study participation, and for 120 days after the last dose of zimberelimab or domvanalimab. See contraception guidelines in Appendix 1. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Women of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
• 1. HBV-HCC: Hepatitis B subjects will be allowed if they meet the following criteria: On antiviral therapy for HBV or HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment. Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.
• 2. HCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug. Successful HCV treatment definition: SVR12.
• Ability to understand and the willingness to sign a written informed consent.
• Willing and able to comply with the requirements and restrictions in this protocol.
• Patients who have received the vector, protein subunit, or nucleic acid COVID-19 vaccines are eligible to enroll.
Exclusion Criteria:
• Prior liver transplant.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug administration.
• History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to:
• 5a. Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying),
• 5b. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs,
• 5c. Clinically significant cardiovascular disease,
• 5d. A condition that may obscure the interpretation of toxicity determination or AEs,
• 5e. History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
• 8a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• 8b. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
• Known history of active bacillus tuberculosis.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses ≤10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease.
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer.
• Prisoners or subjects who are involuntarily incarcerated.
• If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if:
• Has evidence of progression by neurologic symptoms
• Has metastatic brain lesions that require immediate intervention.
• Has carcinomatous meningitis, regardless of clinical stability
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drugs.
• Known hypersensitivity to recombinant proteins, or any excipient contained in the study drug formulations.
Drug: Zimberelimab, Drug: Domvanalimab
Hepatobiliary Cancer, Liver Cancer, Cholangiocarcinoma, Hepatocellular Carcinoma, Liver, Other Digestive Organ
UT Southwestern; Parkland Health & Hospital System
A Study of ASP1002 in Adults for Treatment of Solid Tumors
ASP1002 is a potential new treatment for people with certain solid tumors. Before ASP1002 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help find a suitable dose and check for potential medical problems from the treatment. People in this study will be adults with locally advanced or metastatic solid tumors with high levels of a protein called claudin 4. Metastatic means the cancer has spread to other parts of the body. They will have been previously treated with available standard therapies or refused to receive those treatments. There are 2 main aims of this study. One is to learn if people with certain solid tumors have any medical problems or side effects after receiving different doses of ASP1002. The other is to find a suitable dose of ASP1002 to use in future studies. This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP1002. Any medical problems and side effects will be recorded at each dose. This is done to find suitable doses of ASP1002 to use in Part 2 of the study. The first group will receive the lowest dose of ASP1002. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP1002. The panel will do this for each dose group until all groups have taken ASP1002 or until suitable doses have been selected for Part 2. In Part 2, other different small groups of people will receive ASP1002 with the most suitable doses determined from Part 1. This will help find a more accurate dose of ASP1002 to use in future studies. During both parts of the study, ASP1002 will be given through a vein. This is called an infusion. Each treatment cycle is 21 days long and the infusion is given weekly. People in this study will continue treatment for up to 2 years (32 cycles) until: they have medical problems or side effects that prevent them from continuing treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; they do not come back for treatment. People will visit the clinic several times during each treatment cycle. They will receive ASP1002 infusions 3 times during each treatment cycle. Each infusion could take 15 minutes to 2 hours, depending on the dose. In addition to infusions, other checks will occur during the visit. During these visits, the study doctors will check for any medical problems and side effects from ASP1002. At some visits, other checks will include a medical examination, laboratory tests and vital signs. Vital signs include temperature, pulse, breathing rate, oxygen saturation, and blood pressure. Also, blood and urine samples will be taken. Tumor samples will be taken during certain visits during treatment and when treatment has finished. People will visit the clinic within 7 days after stopping treatment. The study doctors will check for any medical problems and side effects from ASP1002. Other checks will include a medical examination, laboratory tests and vital signs. Then, they may visit the clinic at 30 days (1 month) and 90 days (3 months) after stopping treatment. At the 30-day visit, the study doctors will check for any medical problems and side effects from ASP1002. People will have their vital signs checked and have some laboratory tests. At the 90-day visit, the study doctors will check for any medical problems and side effects from ASP1002 and people will have their vital signs checked. After this, people will continue to visit the clinic every 9 to 12 weeks. This is to check the condition of their cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
All
18 Years and over
Phase 1
NCT05719558
STU-2023-0162
Inclusion Criteria:
• Participant has locally-advanced (unresectable) or metastatic solid tumor which is confirmed by available pathology records or current biopsy.
• For dose escalation, the participant must have one of the following malignancies (for all tumor types, any component of neuroendocrine histology is exclusionary): a. NSCLC - adenocarcinoma, squamous cell carcinoma and adenosquamous are included; large cell carcinoma and sarcomatoid carcinoma are excluded. Note: NSCLC Not Otherwise Specified will require medical monitor consultation prior to study entry; b. urothelial carcinoma (UC); c. colorectal cancer (CRC); d. Prostate adenocarcinoma; e. Ovarian cancer; f. triple-negative breast cancer (TNBC): TNBC defined as unequivocal TNBC histology (estrogen receptor-1 (ER-1) negative/progesterone receptor-negative/ human epidermal growth factor receptor (HER2)-negative). This is defined by < 1% expression of ER and progesterone receptor by immunohistochemistry (IHC) and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not amplified) as per current American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines [Hammond et al, 2010].
• For dose expansion, the participant must have one of the following malignancies (for all tumor types, any component of neuroendocrine histology is not eligible): a. NSCLC - adenocarcinoma, squamous cell carcinoma and adenosquamous are included; large cell carcinoma and sarcomatoid carcinoma are excluded. Note: NSCLC Not Otherwise Specified will require medical monitor consultation prior to study entry; b. UC; c. CRC; d. Tumor type for which a confirmed response was observed during dose escalation.
• Participant has progressed, is intolerant, has refused, or there are no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens).
• Participant has accessible archival tumor tissue (< 6 months old) from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to study intervention; participants without available tissue should undergo a mandatory biopsy. If the participant is unable to undergo a biopsy due to safety concerns, enrollment into the study is at the discretion of the medical monitor. Participant should undergo a tumor biopsy during the treatment period as indicated in the schedule of assessments. Note: Tumor tissue collection (at screening/baseline and on-treatment) is optional for participants enrolled initially in dose levels 1 to 3 in dose escalation; however, protocol de-escalation and expansion of dose levels similar to dose levels 1 to 3 may require collection and processing of screening/baseline and on-treatment tumor samples.
• Participant has at least 1 measurable lesion per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Participant has an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1.
• Participants who have received radiotherapy must have completed this therapy (including stereotactic radiosurgery) at least 2 weeks prior to study intervention administration.
• Participant has predicted life expectancy >/= 12 weeks.
• Participant has adequate organ function prior to start of study intervention. If a participant has received a recent blood transfusion, the laboratory tests must be obtained >/=2 weeks after any blood transfusion.
• Female participant is not pregnant and at least 1 of the following conditions apply:
• a. Not a woman of childbearing potential (WOCBP)
• b. WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 90 days after final study intervention administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for 90 days after final study intervention administration.
• Female participant must not donate ova starting at first administration of study intervention and throughout 90 days after final study intervention administration.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 90 days after final study intervention administration.
• Male participant must not donate sperm during the treatment period and for 90 days after final study intervention administration.
• Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 90 days after final study intervention administration.
• Participant agrees not to participate in another interventional study while receiving study intervention in the present study.
Exclusion Criteria:
• Participant weighs < 40 kg.
• Participant has ongoing toxicity >/= grade 2 per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 considered clinically significant and attributable to prior antineoplastic therapies.
• Participant has untreated or active central nervous system (CNS) metastases. Participants with previously treated CNS metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study intervention and are not requiring immunosuppressive doses of systemic steroids (equivalent to > 10 mg per day of prednisone) for longer than 2 weeks.
• Participant has an active autoimmune disease. Participant with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
• Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention or currently has an uncontrolled illness including, but not limited to, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome or right bundle branch block with left anterior hemiblock (bifascicular block).
• Participant has a corrected corrected QT interval (QTcF) interval (single electrocardiogram (ECG)) > 470 ms within 7 days prior to the first study intervention administration on day 1.
• Participant has left ventricular ejection fraction (LVEF) < 45% noted in screening echocardiogram (ECHO). Any clinically significant findings from this ECHO should be discussed with the medical monitor.
• Participant is known to have human immunodeficiency virus (HIV) infection. However, participants with HIV infection with CD4+ T cell counts >/=350 cells/μL and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6 months are eligible. Note: No HIV testing is required at screening unless mandated per local requirements.
• Participant has any of the following per screening serology test:
• a. Hepatitis A virus antibodies immunoglobulin (IgM)
• b. Positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B Deoxyribonucleic Acid (DNA). Participant with negative HBsAg, positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antibody (anti-HBs) are eligible if hepatitis B DNA is undetectable
• c. hepatitis C virus (HCV) antibodies unless HCV Ribonucleic acid (RNA) is undetectable
• Participant has a history of drug-induced pneumonitis, interstitial lung disease (ILD), currently has pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
• Participant has an infection requiring intravenous antibiotics within 14 days prior to study intervention administration.
• Participant has received a prior allogeneic bone marrow or solid organ transplant.
• Participant has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study intervention.
• Participant with recent positive antigen test for Coronavirus Disease 2019 (COVID-19) within 10 days prior to study intervention administration. Note: Participants who are asymptomatic after 10 days from the first positive antigen test may be enrolled.
• Participant has received any investigational therapy or antineoplastic therapy or other immunotherapy within 21 days or 5 half-lives, whichever is shorter, prior to the first dose of study intervention. Note: Participants with prostate adenocarcinoma who do not have a bilateral orchiectomy should continue androgen deprivation therapy (ADT) during the study. A participant with epidermal growth factor receptor (EGFR), receptor tyrosine kinase (encoded by the gene ROS1), or anaplastic lymphoma kinase (ALK) mutation-positive NSCLC is allowed to remain on EGFR tyrosine receptor inhibitor, neurotrophic tyrosine receptor kinase inhibitor or ALK inhibitor therapy until 4 days prior to the start of study intervention administration.
• Participant requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to ASP1002 administration. Participants using a physiologic replacement dose of corticosteroids equivalent to 10 mg per day of prednisone or less are allowed, as is receiving a single dose of systemic corticosteroids, or receiving systemic corticosteroids as premedication for radiologic imaging contrast is eligible.
• Participant was discontinued from prior immunomodulatory therapy due to a grade >/=3 toxicity that was mechanistically related (e.g., immune-related) to the agent and deemed life-threatening.
• Participant is expected to require another form of antineoplastic therapy while on study intervention.
• Participant has another malignancy requiring active therapy; (other than those indicated in Inclusion Criterion No. 1).
• Participants who have received prior anti-CD137 therapy.
• Participant has received a live vaccine against infectious diseases within 28 days prior to initiation of study intervention.
• Participant has any condition makes the participant unsuitable for study participation.
• Participant has a known or suspected hypersensitivity to ASP1002 or any components of the formulation used.
Drug: ASP1002
Advanced Solid Tumors, Breast - Female, Breast - Male, Colon, Lung/Thoracic, Ovary, Prostate, Urinary Bladder
Solid Tumor,, Malignancy,, Metastasis,, cancer,, ASP1002,, Pharmacokinetics
UT Southwestern
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma (EMERGE 101)
This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
2 Years to 30 Years old
PHASE1
NCT05734066
STU-2023-0156
Key
Inclusion Criteria:
Age
* Participant must meet the following age requirements at the time the informed consent form (ICF) (and assent form, if applicable) is signed:
* Phase 1 Part 1: participants must be ≥ 2 to \< 18 years of age.
* Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
* Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
Type of Participant and Disease Characteristics
* Participant has a confirmed solid tumor
* The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
* The participant has adequate liver function, evidenced by the following laboratory values:
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
* Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants with Gilbert's syndrome who must have bilirubin \< 3 × institutional ULN).
* The participant has adequate bone marrow function, evidenced by the following:
* Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (independent of growth factor support within 1 week of screening laboratories).
* Platelets ≥ 100 × 109/L (without platelet transfusion within previous 7 days of screening laboratories).
* Hemoglobin ≥ 8 g/dL (note: may have been transfused).
* The participant has an adequate renal function:
* Calculated creatinine clearance (use Cockcroft-Gault formula for participants ≥ 18 years; Schwartz equation for participants \< 18 years) ≥ 60 mL/min.
* The participant has an adequate cardiac function:
* Left ventricular ejection fraction or shortening fraction per institutional norm ≥ institutional lower level of normal.
* The participant has creatine phosphokinase ≤ 2.5 × institutional ULN.
Weight
* The participant has body weight ≥ 15 kg.
Sex and Contraceptive/Barrier Requirements
Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 4 months after the last dose of study intervention:
* Refrain from donating sperm.
PLUS, either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
* Must agree to use contraception/barrier as detailed below:
* Agree to use a male condom with female partner and use of an additional highly effective contraceptive method with a failure rate of \< 1% per year when having sexual intercourse with a Woman of childbearing potential (WOCBP) who is not currently pregnant.
* Note: male participants who are azoospermic (vasectomized or due to a medical cause) are still required to follow the protocol-specified contraception/barrier criteria.
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a Woman of nonchildbearing potential (WONCBP). OR
* Is a WOCBP and using an acceptable contraceptive method during the study intervention period (at least 7 months after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 7 days before the first dose of study intervention.
* If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Additional requirements for pregnancy testing during and after study intervention.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Informed Consent
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Key Exclusion Criteria:
Medical Conditions
* corrected QT interval (QTc) prolongation defined as a QTc ≥ 470 ms using the Bazett formula.
* Known symptomatic Central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued high dose steroid treatment for these metastases for at least 2 weeks, and are neurologically stable (physiologic doses of steroids and short courses of steroids for other indications are acceptable).
* Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy, hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse events (AEs) not constituting a safety risk based on the investigator's judgement are acceptable.
* An uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with participation in this study.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high-risk for treatment complications.
Prior/Concomitant Therapy
* Received prior treatment with lurbinectedin or trabectedin.
* Received prior treatment with any investigational product within 4 weeks of first infusion of study intervention. Observational studies are permitted.
* Received live or live attenuated vaccines within 4 weeks of the first dose of study treatment or plans to receive live vaccines during study participation. Administration of inactive vaccines or messenger ribonucleic acid (mRNA) vaccines (for example, inactivated influenza vaccines or COVID-19 vaccines) are allowed.
* Had major surgery ≤ 4 weeks or radiation therapy ≤ 2 weeks prior to enrollment unless fully recovered. Prior palliative radiotherapy is permitted, provided it was completed at least 2 weeks prior to participant enrollment.
* Received prior allogeneic bone marrow transplantation or solid organ transplant.
* Received chemotherapy ≤ 3 weeks prior to start of study intervention.
Diagnostic Assessments
* Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or Polymerase chain reaction (PCR) test for HCV RNA if HCV antibody test is positive).
* Human immunodeficiency infection at screening (positive anti-HIV antibody).
Other Exclusions
* Has a known or suspected hypersensitivity to any of the components of the study intervention.
* The participant or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator DRUG: Lurbinectedin
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Ewing Sarcoma, Sarcoma
Solid Tumors, lurbinectedin, ewing's sarcoma, soft tissue sarcoma, sarcomas
Children’s Health
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
* Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
* Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
* Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
* Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
* Measurability of disease:
* Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* FGFR inhibitor specific requirements:
* Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
* Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
* Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy.
* Known or suspected history of uncontrolled CNS metastases.
* Current evidence of corneal keratopathy or retinal disorder.
* Have a history and/or current evidence of extensive tissue calcification.
* Any serious unresolved toxicities from prior therapy.
* Significant cardiovascular disease.
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
* Active uncontrolled systemic infection or other clinically significant medical conditions.
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled. DRUG: LOXO-435, DRUG: Pembrolizumab
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
Selinexor in Maintenance Therapy After Systemic Therapy for Participants with P53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)
The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v 1.1\]) after completing at least 12 weeks of platinum-based therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years and over
PHASE3
NCT05611931
STU-2023-0654
Inclusion Criteria:
* At least 18 years of age at the time of signing informed consent.
* Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinosarcoma.
* TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.
* Completed a single line, at least 12 weeks of platinum-based therapy (not including adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed partial or complete response (PR or CR) by imaging, according to RECIST version 1.1. The participants should have received treatment for:
Primary Stage IV disease, defined as:
* had a primary or later debulking surgery during first-line platinum-based therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR
* had a primary or later debulking surgery during first-line platinum-based therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease) and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR
* had no surgery and achieved PR or CR after at least 12 weeks platinum-based chemotherapy
OR
At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy and/or immunotherapy for Stage I-IV disease), defined as:
* had Stage I - III disease at diagnosis and received, at initial diagnosis, adjuvant chemotherapy and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse,
* had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
* had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse.
* Previous treatment with anti-programmed cell death protein 1(PD-1) or anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant biologic agents (e.g., bevacizumab, trastuzumab) is allowed.
* Must be able to initiate study drug 3 to 8 weeks after completion of their final dose of chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Participants must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
* Hepatic function: total bilirubin up to less than (\<) 3\*upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\*ULN in participants without liver metastasis. For participants with known liver involvement of their tumor: AST and ALT (\<=) 5\*ULN
* Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.5\*10\^9/liter (L); platelet count \>= 100\*10\^9/L; hemoglobin \>= 9.0 gram per deciliter (g/dL) per local laboratory results
* Renal function: estimated creatinine clearance (CrCl) of \>= 20 milliliter per minute (mL/min), calculated using the standard local formula, as applicable
• In the opinion of the Investigator, the participant must: * Have a life expectancy of at least 12 weeks, and * Be fit to receive investigational therapy * Premenopausal females of childbearing potential must have a negative pregnancy test (serum β-human chorionic gonadotropin test) prior to the first dose of study drug. Female participants of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 90 days following the last dose of study drug. * Written informed consent signed in accordance with federal, local, and institutional guidelines prior to the first screening procedure.
Exclusion Criteria:
* Participants meeting any of the following exclusion criteria are not eligible to enroll in this study:
* Has any uterine sarcomas (carcinosarcomas - not excluded), clear cell or small cell carcinoma with neuroendocrine differentiation
* Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1 (C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at least 1 week post transfusion
* Concurrent systemic steroid therapy higher than physiologic dose (\> 10 milligram per day \[mg/day\] of prednisone or equivalent). Systemic steroid therapy as pre-medication for taxane is allowed
* Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
* Not recovered from major surgery \<= 28 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted
* Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade \> 1, with the exception of alopecia. In specific cases, participants whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor
* Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect evidence of disease progression.
* Any gastrointestinal dysfunctions that could interfere with the absorption of selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 \> grade 1).
* Participants unable to tolerate two forms of antiemetics for at least 2 cycles will not be eligible for the trial.
* Active, ongoing or uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of screening.
* Serious psychiatric or medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.
* Previous treatment with an XPO1 inhibitor.
* Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression prior to randomization.
* Participants who received any systemic anticancer therapy including investigational agents \<= 3 weeks (or \<= 5 half-lives of the drug \[whichever is shorter\]) prior to C1D1.
* Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery during the on-treatment study period.
* Other malignant disease with disease-free \<= 3 years except: curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma in situ (DCIS) of the breast.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor, or other agents used in the study.
* Active brain metastases (e.g., stable for \< 8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose for at least 1 month before randomization).
* Females who are pregnant or lactating.
* Any other life-threatening illness, active medical condition, organ system dysfunction, or serious active psychiatric issue which, in the Investigator's opinion, could compromise the participant's safety or the participant's ability to remain compliant with study procedures. DRUG: Selinexor, DRUG: Matching Placebo for selinexor
Endometrial Cancer, Corpus Uteri
Selinexor, KPT-330, Advanced or Recurrent Endometrial Carcinoma, XPORT-EC, ENGOT-EN20, GOG-3083, XPORT-EC-042, p53 wild-type, Tumor protein 53 wild-type
UT Southwestern; Parkland Health & Hospital System
LOcoregional Vs Systemic Therapy in Patients with BCLC Stage B HCC (LOST-B)
The purpose of this research study is to compare the effectiveness and safety of two standard of care treatments in people who have been diagnosed with hepatocellular carcinoma (HCC).This research study is being done to compare atezolizumab/bevacizumab to locoregional therapy with either transarterial chemoembolization (TACE) or transarterial radioembolization (TARE).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years and over
PHASE2
NCT05537402
STU-2022-0848
Inclusion Criteria:
• Patients with confirmed HCC by imaging (LI-RADS 5) or histopathology
• Treatment-naïve, liver localized (intermediate-stage), i.e., beyond Milan Criteria (one tumor ≤5 cm, or two to three tumors, each ≤3 cm) and not amenable to curative surgery, liver transplantation, or local ablation and no evidence of extrahepatic disease or vascular invasion.
• Child Pugh class A
• Age ≥18 years at time of screening
• ECOG Performance Status 0 or 1
• Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV NA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/ml or under the limit of detection per local lab standard) are not required to start antiviral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
• Patients with HCV infection, defined by presence of detectable antibody or RNA, should have management of this disease per local institutional practice throughout the study.
• At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria: • Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase * Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter
• Adequate organ and marrow function at enrollment as defined below: (a) Hemoglobin ≥9.0 g/dL Patients may be transfused to meet this criterion. (b) Absolute neutrophil count ≥1500/μL (c) Platelet count ≥75000/μL (d) Total bilirubin ≤3 × the upper limit of normal (ULN) (e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN (f) Albumin ≥2.8 g/dL (g) Lymphocyte count ≥0.5 X 109/L (500/µL) (h) 2+ proteinuria or less urine dipstick reading or normal UA with less than 100 mg/dL protein (i) Calculated creatinine clearance (CL) ≥30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine CL (j) For patients not receiving therapeutic anticoagulation: INR or aPTT ≤2 × ULN
• Upper endoscopy to evaluate varices and risk of bleeding is required within one year prior to randomization
• Negative HIV test at screening
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for 6 months following completion of therapy. Women must refrain from donating eggs during this same period. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. • A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Chemotherapy, radiotherapy, or other cancer therapy within 3 months prior to starting study treatment.
• Any prior immunotherapy for malignancy.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Patients with infiltrative-type HCC
• Definite macrovascular invasion or distant metastatic disease at randomization
• Clinically significant ascites, requiring non-pharmacological intervention (e.g., paracentesis) to maintain control within past 6 months
• History of hepatic encephalopathy within past 6 months
• Actively listed or under evaluation for liver transplantation
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active tuberculosis
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• History or evidence upon physical or neurological examination of central nervous system dysfuction
• Current or recent (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk.
• History of leptomeningeal disease
• Uncontrolled tumor-related pain. Patients requiring pain medication should be on stable regimen prior to study entry.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus who are on an insulin are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: * Rash must cover \<10% of body surface area. * Disease is well controlled at baseline and requires only low-potency topical corticosteroids. * There is no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the 12 months prior to Day 1 of Cycle 1.
• Systemic immunostimulatory agents (including, but not limited to, IFNs and IL-2) are prohibited within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during study treatment.
• History of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
• History of grade ≥4 venous thromboembolism.
• Non-healing wound, active ulcer, or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require wound examinations every 3 weeks.
• History of abdominal fistula or GI perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment.
• History of grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within one month of screening
• Core biopsy or other minor surgical procedure, excluding vascular access device, within 7 days prior to initiation of study treatment.
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study treatment, or anticipation of need for major surgical procedure during the course of the study (Note: Biopsy and endoscopy are not considered surgery so would not be exclusion criteria)
• Uncontrolled hypertension defined by a systolic pressure \>150 mmHg or diastolic pressure \>90 mmHg, with or without antihypertensive medication. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
• History of allogeneic stem cell or organ transplantation
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (except for noted HBV or HCV as detailed above), symptomatic congestive heart failure, poorly controlled diabetes mellitus, unstable angina pectoris, uncontrolled cardiac arrhythmia, active Interstitial Lung Disease (ILD), serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥1 year before randomization and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease
• History of active primary immunodeficiency.
• Patients co-infected with HBV and hepatitis D virus (HDV). (HBV infection is defined above; HDV positive infection is indicated by the presence of anti-HDV antibodies).
• Treatment with a live, attenuated vaccine (e.g., FluMist®) within 4 weeks prior to Day 1 of Cycle 1, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab. 43 Subjects must have recovered from prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management).
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab or bevacizumab or other agents used in study.
• Subjects must not be pregnant or breastfeeding during the study treatment, or have the intention of becoming pregnant during the study treatment or within 6 months after the final dose of study treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study treatment.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of Patients who receive mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
DRUG: Atezolizumab and bevacizumab, RADIATION: transarterial chemoembolization (TACE) or transarterial radioembolization (TARE
Hepatocellular Carcinoma, Liver
UT Southwestern; Parkland Health & Hospital System
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 1/Phase 2
NCT05440708
STU-2022-0622
Inclusion Criteria:
• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Age ≥18 years at the time of informed consent.
• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.
• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.
• Able to swallow tablets.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 10^9/L (500/μL).
• Platelet count ≥75 × 10^9/L (75,000/μL) without transfusion.
• Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
• Serum albumin ≥28 g/L (2.8 g/dL).
• AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
• Serum bilirubin ≤2 mg/dL.
• Adequate renal function defined as either:
• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
• 24-hour urine collection.
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
• Child-Pugh class A or B7 within 7 days prior to enrollment.
• Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:
• Have a negative serum pregnancy test at screening.
• Not be breastfeeding or lactating.
• Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.
• Males must:
• Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
• Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
• Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization. Cohort A:
• In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. Cohort B:
• In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information. Cohort C:
• In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
• Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.
Exclusion Criteria:
• Pregnant or breastfeeding.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• History of leptomeningeal disease.
• Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
• Previous therapy with:
• Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin).
• Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
• Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy. Note: Participants with chronic hepatitis C virus (HCV) infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV ribonucleic acid (RNA).
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:
• Chronic pancreatitis.
• Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
• Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
• Is unable to understand and to comply with study instructions and requirements. Cohort B: In addition to the general exclusion criteria, participants enrolled in Cohort B must fulfill the following additional exclusion criteria:
• Discontinued prior treatment with anti-PD-1 or anti-PD-L1 for any reason other than disease progression. Cohort C: In addition to the general exclusion criteria and Cohort B criteria, participants enrolled in Cohort C must fulfill the following additional exclusion criteria:
• Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
• Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC. However, participant may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows <1 g of protein in 24 hours, the participant is eligible.
• Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants. Prophylactic anticoagulants (eg, low-dose warfarin with target INR <1.5 × ULN or low-dose low molecular weight heparin) are allowed.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
• History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
• Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc), congestive heart failure, hemoptysis, or pulmonary embolism.
• Participant has experienced a fistula. Cohorts B and C: In addition to the general exclusion criteria and the cohort-specific criteria listed above, participants enrolled in Cohorts B and C must fulfill the following additional exclusion criteria:
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of pembrolizumab treatment.
• Active or history of immune-mediated disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, participants with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2 weeks prior to initiation of study treatment. Participants receiving low-dose corticosteroids (equivalent of prednisone 10 mg/day or lower) or who receive pulse corticosteroids due to intravenous (IV) contrast allergy are not excluded.
• Active tuberculosis.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab
Hepatocellular Carcinoma, Liver
Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert
UT Southwestern; Parkland Health & Hospital System
A Study of BGB-24714 as Monotherapy and With Combination Therapies in Participants With Solid Tumors
This study aims to understand how safe and well-tolerated a drug called BGB-24714 is when used alone, or in combination with chemotherapy or radiation therapy, for people with advanced or spreading solid tumors. The main objective is to identify the highest tolerable dose or the highest administered dose of BGB-24714. Additionally, the study aims to identify the most suitable doses for further investigation in larger groups of participants.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Andrew Wang
ALL
18 Years to old
PHASE1
NCT05381909
STU-2023-1108
Key Eligibility Criteria :
• Participants must sign a written informed consent form (ICF); and agree to comply with study requirement
• Phase 1a (Dose Escalation): Part A, A-CN, and B: Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor previously treated with standard systemic therapy or for whom treatment is not available or not tolerated Note: Only Chinese participants will be eligible for Part A-CN. Part C: Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III Non-small cell lung cancer (NSCLC) suitable for definitive chemoradiotherapy (CRT) Part D: Participant with locally advanced, histologically confirmed inoperable esophageal squamous cell carcinoma (ESCC) suitable for definitive CRT Phase 1b (Dose Expansion): Participants with histologically or cytologically confirmed solid tumors of selected types previously treated with standard therapy.
• Participants must be able to provide formalin-fixed paraffin embedded (FFPE) tumor tissue sample.
• Phase 1a Part A, A-CN, B and Phase 1b: ≥ 1 measurable lesion per Response evaluation criteria in solid tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Key
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
• Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
• Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
• Clinically significant infection requiring systemic therapy ≤ 14 days before the first dose of study drug(s).
• Prior exposure to agents with second mitochondria-derived activator of caspases (SMAC) mimetics, or other Inhibitors of apoptosis proteins (IAPs) antagonists. NOTE: Other protocol defined inclusion/exclusion criteria may apply.
• Participants must sign a written informed consent form (ICF); and agree to comply with study requirement
• Phase 1a (Dose Escalation): Part A, A-CN, and B: Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor previously treated with standard systemic therapy or for whom treatment is not available or not tolerated Note: Only Chinese participants will be eligible for Part A-CN. Part C: Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III Non-small cell lung cancer (NSCLC) suitable for definitive chemoradiotherapy (CRT) Part D: Participant with locally advanced, histologically confirmed inoperable esophageal squamous cell carcinoma (ESCC) suitable for definitive CRT Phase 1b (Dose Expansion): Participants with histologically or cytologically confirmed solid tumors of selected types previously treated with standard therapy.
• Participants must be able to provide formalin-fixed paraffin embedded (FFPE) tumor tissue sample.
• Phase 1a Part A, A-CN, B and Phase 1b: ≥ 1 measurable lesion per Response evaluation criteria in solid tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Key
Exclusion Criteria:
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
• Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
• Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
• Clinically significant infection requiring systemic therapy ≤ 14 days before the first dose of study drug(s).
• Prior exposure to agents with second mitochondria-derived activator of caspases (SMAC) mimetics, or other Inhibitors of apoptosis proteins (IAPs) antagonists. NOTE: Other protocol defined inclusion/exclusion criteria may apply.
DRUG: BGB-24714, DRUG: Paclitaxel, DRUG: Carboplatin, DRUG: Docetaxel
Solid Tumor, Adult, Lung/Thoracic
Solid tumors, Advanced Solid Tumors, Metastatic Solid Tumors
UT Southwestern
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months and over
PHASE1
NCT05286801
STU-2022-0879
Inclusion Criteria:
* Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit
* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
* Age; Maximum Serum Creatinine (mg/dL)
* 1 to \< 2 years; Male: 0.6; Female: 0.6
* 2 to \< 6 years; Male: 0.8; Female: 0.8
* 6 to \< 10 years; Male: 1; Female: 1
* 10 to \< 13 years; Male: 1.2; Female: 1.2
* 13 to \< 16 years; Male: 1.5; Female: 1.4
* \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
* Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level
* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:
* Corticosteroids:
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients \< 18 years old at enrollment, who have known hepatitis B or C
* Patients \>= 18 years old at enrollment with:
* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Fludeoxyglucose F-18, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tiragolumab, PROCEDURE: X-Ray Imaging
Atypical Teratoid/Rhabdoid Tumor, Epithelioid Sarcoma, Kidney Medullary Carcinoma, Malignant Solid Neoplasm, Poorly Differentiated Chordoma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Chordoma, Recurrent Epithelioid Sarcoma, Recurrent Kidney Medullary Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Rhabdoid Tumor, Refractory Atypical Teratoid/Rhabdoid Tumor, Refractory Chordoma, Refractory Epithelioid Sarcoma, Refractory Kidney Medullary Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Rhabdoid Tumor, Rhabdoid Tumor, Bones and Joints, Soft Tissue
Children’s Health
Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis (LIVERATION)
This is a clinical trial in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B7 (CPB7) cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 3
NCT05201404
STU-2022-1196
Inclusion Criteria:
• Males and females at least 18 years of age.
• Diagnosis of HCC:
• For patients without cirrhosis at the time of diagnosis, histologic confirmation is required (archival tissue is acceptable).
• For patients with underlying cirrhosis at the time of diagnosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Marrero 2018).
• HCC is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
• HCC has progressed on at least 1, but no more than 2, prior systemic treatment regimens; prior locoregional therapy is allowed.
• Barcelona Clinic Liver Cancer (BCLC) Stage B or C (Llovet 1999).
• Prior HCC treatment was discontinued for at least 2 weeks prior to the Baseline Visit.
• Measurable disease by RECIST v1.1 (Eisenhauer 2009).
• ECOG PS of ≤ 1.
• Cirrhosis classified as CPB7; if ascites is used as a scoring criterion, it must be classified as Grade ≥2 by the Clinical Practice Guidelines of the European Association for the Study of the Liver (EASL 2010).
• The following laboratory values must be documented within ten days prior to the first dose of study drug:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count at least 75 × 10^9/L
• Creatinine clearance at least 50 mg/dL (estimated glomerular filtration rate by the Cockcroft-Gault or the Modification of Diet in Renal Disease methods)
• AST and ALT ≤ 5 × the upper limit of normal (ULN)
• Total bilirubin ≤ 3.0 mg/dL
• Serum albumin ≥ 2.8 g/dL.
• Life expectancy of ≥ 6 weeks.
• For women of childbearing potential, negative serum pregnancy test result.
• Provide written informed consent to participate.
• Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures.
Exclusion Criteria:
• Receipt of >2 prior systemic drug therapies for HCC.
• Receipt of systemic cancer therapy, immunomodulatory drug therapy, immunosuppressive therapy, or corticosteroids > 20 mg/day prednisone or equivalent within 14 days prior to the Baseline Visit or concurrently during the trial.
• Locoregional treatment within 4 weeks prior to the Baseline Visit.
• Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.
• Use of any investigational agent within 4 weeks prior to the Baseline Visit.
• Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product (see Section 12.2).
• Child-Pugh Class A, B8/9, or C cirrhosis.
• Hepatic encephalopathy.
• Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
• Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
• Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
• Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
• Liver transplant.
• Active malignancy other than HCC.
• Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4).
• Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
• History of, or ongoing, cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 470 msec (patients with bundle branch block will not be excluded for QTc reasons).
• Pregnant or lactating female.
• Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient's circumstances while on study drug.
• Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
• Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with trial participation or study drug administration; may interfere with the informed consent process and/or with compliance with the requirements of the trial; or may interfere with the interpretation of trial results and, in the Investigator's opinion, would make the patient inappropriate for entry into this trial.
Drug: Namodenoson, Drug: Placebo
Hepatocellular Carcinoma, Cirrhosis, Liver
Hepatocellular carcinoma, HCC, Liver cancer, Child-Pugh Class B7 cirrhosis, CPB7
UT Southwestern; Parkland Health & Hospital System
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors. In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
All
18 Years and over
Phase 1
NCT05176483
STU-2022-0177
Inclusion Criteria:
• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.
• Dose-Escalation Cohorts: Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
• Expansion Cohort 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.
• Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.
• Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component.
• Must have radiographically progressed after a combination therapy consisting of a PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.
• Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
• Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
• Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
• Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior first-line platinum-based combination therapy, including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.
• Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
• Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.
• Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.
• Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.
• No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.
• Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.
• Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
• Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
• Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
• Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
• For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
• For expansion cohorts only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
• Karnofsky Performance Status (KPS) ≥ 70%.
• Adequate organ and marrow function.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
• For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.
• Administration of a live, attenuated vaccine within 30 days prior to enrollment.
• Uncontrolled, significant intercurrent or recent illness.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.
• Subjects with inadequately treated adrenal insufficiency.
• Pregnant or lactating females.
• Any other active malignancy within two years before first dose of study treatment, except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
• For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
• For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
• For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
• For Cohort 7 (HCC):
• Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).
• Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
• Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.
• Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
• For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.
• For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
• For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):
• Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Note: Additional Inclusion and Exclusion criteria may apply.
Drug: XL092, Drug: Nivolumab, Drug: Ipilimumab, Drug: Nivolumab, Drug: Nivolumab, Drug: Nivolumab + Relatlimab
Renal Cell Carcinoma, Metastatic Castration-resistant Prostate Cancer, Urothelial Carcinoma, Solid Tumor, Hepatocellular Carcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Head and Neck Squamous Cell Carcinoma, Kidney, Prostate, Urinary Bladder
UT Southwestern
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, As a Single Agent in Advanced Solid Tumor Patients and in Combination with Fulvestrant in Patients with Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors, RLY-2608 + fulvestrant and RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) combination arms for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
ALL
18 Years and over
PHASE1
NCT05216432
STU-2023-1126
Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment
• Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment. Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively. Key Inclusion for RLY-2608 Single Agent Arm * \[For Part 1\]: Evaluable disease per RECIST v1.1 * \[For Part 2\]: Measurable disease per RECIST v1.1 * Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy. * Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor * Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types: Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations Key Inclusion for Combination Arms * \[For Part 1 and Part 2\]: Evaluable disease per RECIST v1.1 * \[For Part 1 and Part 2\]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative therapy and must have been previously treated with GnRH agonist at least 4 weeks prior to start of study drug * \[For Part 1 and Part 2\]: Had previous treatment for breast cancer with:
• ≤1 line of chemotherapy in the metastatic setting
• ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, in either the adjuvant and/or metastatic setting
• ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
• ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment \[For RLY-2608 + fulvestrant arm; Part 2, Group 2\]: Received prior treatment with a PI3Kα inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome. Key Exclusion Criteria Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm, Part 2, Group 2). Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination. For triple combination arms only: history of pneumonitis or interstitial lung disease. For the single agent and combination arms other than with ribociclib: mean QT interval corrected using Fridericia's formula (QTcF) \>480 msec. For the combination arms with ribociclib: mean QTcF ≥450 msec. Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a familial history of prolonged QT syndrome. Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
• Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment. Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively. Key Inclusion for RLY-2608 Single Agent Arm * \[For Part 1\]: Evaluable disease per RECIST v1.1 * \[For Part 2\]: Measurable disease per RECIST v1.1 * Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy. * Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor * Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types: Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations Key Inclusion for Combination Arms * \[For Part 1 and Part 2\]: Evaluable disease per RECIST v1.1 * \[For Part 1 and Part 2\]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative therapy and must have been previously treated with GnRH agonist at least 4 weeks prior to start of study drug * \[For Part 1 and Part 2\]: Had previous treatment for breast cancer with:
• ≤1 line of chemotherapy in the metastatic setting
• ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, in either the adjuvant and/or metastatic setting
• ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
• ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment \[For RLY-2608 + fulvestrant arm; Part 2, Group 2\]: Received prior treatment with a PI3Kα inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome. Key Exclusion Criteria Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm, Part 2, Group 2). Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination. For triple combination arms only: history of pneumonitis or interstitial lung disease. For the single agent and combination arms other than with ribociclib: mean QT interval corrected using Fridericia's formula (QTcF) \>480 msec. For the combination arms with ribociclib: mean QTcF ≥450 msec. Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a familial history of prolonged QT syndrome. Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
DRUG: RLY-2608, DRUG: Fulvestrant, DRUG: Palbociclib 125mg, DRUG: Ribociclib 400mg, DRUG: Ribociclib 600mg
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Breast - Female, Breast - Male
UT Southwestern
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder
UT Southwestern
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years and over
PHASE1
NCT05007782
STU-2023-0042
Key
Inclusion Criteria:
* Disease:
* Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
* Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
* Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-\[L\]1) monoclonal antibody monotherapy.
* Part D: Individuals with pathologically confirmed select advanced solid tumors.
* Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
* Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
* Adequate organ function.
* Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
* Tissue requirement:
* Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
* Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis.
Key Exclusion Criteria:
* Concurrent anticancer treatment.
* Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (\< 28 days), chemotherapy (\< 21 days), targeted small molecule therapy (\< 14 days), hormonal therapy or other adjunctive therapy (\< 14 days) or radiotherapy (\< 21 days).
* Any prior CCR8 directed therapy.
* Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
* Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for \> 2 years.
* History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
* History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
* History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
* Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
* Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
* Positive serum pregnancy test or breastfeeding female.
* Live vaccines within 30 days prior to first dose.
* Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply. DRUG: Denikitug, DRUG: Zimberelimab
Advanced Solid Tumor, Colon, Lung/Thoracic, Other Digestive Organ, Rectum, Stomach, Unknown Sites
UT Southwestern
NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies
Multicenter, open-label study in patients with advanced or metastatic solid tumor malignancies to evaluate the safety, tolerability, and preliminary anti-tumor efficacy, PK, and pharmacodynamics of continuously dosed NP-G2-044 monotherapy and NP-G2-044 in combination with anti-PD-1 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
ALL
18 Years and over
PHASE1
NCT05023486
STU-2022-0778
Inclusion Criteria:
• Male or female ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Life expectancy of \> 6 months;
• Abilty to swallow capsules and tablets;
• Adequate organ and bone marrow function, defined by the following: ANC \>1500 cells/μL; Hemoglobin \>9.0 g/dL; Platelet count \>100,000 cells/μL; Total bilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upper limit of normal (ULN); Creatinine clearance ≥50 mL/min; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone \[FSH\] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.
• Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (eg, male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and
• Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements. Inclusion Criteria for NP-G2-044 Monotherapy: Patients must meet all the following criteria to receive NP-G2-044 monotherapy in the study:
• Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive;
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.;
• For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have:
• Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or
• Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC).
• For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy Inclusion Criteria for NP-G2-044 Combination Therapy Patients must meet 1 of the following criteria to receive NP-G2-044 in combination with anti-PD-1 therapy in the study:
• Have initiated anti-PD-1 therapy in accordance with the package insert and have been receiving the anti-PD-1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease, or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1. or Have discontinued prior anti-programmed death-1/programmed death ligand-1 (PD- \[L\]1) therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD 1 therapy.
Exclusion Criteria:
• Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy.
• Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and reviewed by the Novita Medical Monitor or designee.
• Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible
• Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (ie, not requiring steroids) ≥4 weeks prior to study enrollment;
• QTc by Fridericia method \>470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;
• Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;
• Received prior solid organ transplantation;
• Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);
• Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;
• History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; or
• Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria.
DRUG: NP-G2-044 Monotherapy, DRUG: Anti-PD-1 Therapy, DRUG: NP-G2-044 Combination therapy
Advanced or Metastatic Solid Tumor Malignancies, Breast - Female, Cervix, Other Female Genital
Advanced or Metastatic Solid Tumor Malignancies
UT Southwestern
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE3
NCT04939090
STU-2021-1170
Inclusion Criteria:
* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* Diagnosis of advanced cancer
* Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
* The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite...." question that requires a patient response on a 0-10 numeric rating scale
* Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
* Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
* No use of androgens, progesterone analogs, or other appetite stimulants within the past month
* Patient should not have poorly controlled hypertension or congestive heart failure at registration
* Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
* Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
* Patient should not have had a previous blood clot at any time in the past
* No history of poorly controlled diabetes
* No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
* No history of hypersensitivity to olanzapine or megestrol acetate
* No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 14 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Estimated life expectancy of 3 months or longer
* Serum creatinine =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Fasting glucose \< 140 mg/dL
* Granulocytes \> 1000/hpf
* No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
* In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
* Psychiatric illness which would prevent the patient from giving informed consent
* Medical condition such as uncontrolled infection (including human immunodeficiency virus \[HIV\]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients who cannot swallow oral formulations of the agents
* Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
* No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate) DRUG: Olanzapine, DRUG: Megestrol Acetate, OTHER: Questionnaire Administration
Advanced Malignant Solid Neoplasm, Anorexia, Hematopoietic and Lymphoid Cell Neoplasm, Anklylosing Spondylitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Heart, Hodgkins Lymphoma, Ill - Defined Sites, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Psychiatric Disorders, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern
PLAN Intervention to Enhance Engagement of Latino Cancer Patients in Advanced Care Planning
This trial tests whether Planning for Your Advance Care Needs (PLAN) intervention works to enhance Latino patients' understanding of and engagement in advanced care planning. The PLAN intervention may be an effective method to help people with cancer plan for and talk about advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Mary Paulk
ALL
18 Years and over
NA
NCT04889144
STU-2021-0192
Inclusion Criteria:
* Identifying ethnically as Latino.
* Locally advanced or metastatic cancer and/or have experienced disease progression on at least first-line chemotherapy.
* Ability to provide informed consent.
Exclusion Criteria:
* Not fluent in English or Spanish.
* Severely cognitively impaired (as measured by Short Portable Mental Status Questionnaire scores of \>= 6 to be delivered by trained study research staff during screening).
* Too ill or weak to complete the interviews (as judged by interviewer).
* Currently receiving palliative care/hospice at the time of enrollment (to allow prediction of \[advanced care planning\] ACP).
* Children and young adults under age 18.
* Patients deemed inappropriate for the study by their treating oncologist. OTHER: Communication Intervention, OTHER: Best Practice, OTHER: Questionnaire Administration
Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Cervix, Colon, Esophagus, Gall Bladder, Head and Neck, Liver, Lung/Thoracic, Lymphoma, Other Female Genital, Other Urinary, Ovary, Pancreas, Sarcoma, Stomach
advance care planning, Latinos, communication
UT Southwestern; Parkland Health & Hospital System
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months to 30 Years old
PHASE1
NCT04870944
STU-2023-0600
Inclusion Criteria:
* Parts A and B1: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* Part B2 (relapsed/refractory osteosarcoma): Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
* Part B2: Patients with relapsed or refractory osteosarcoma
* Part A: Patients must have either measurable or evaluable disease
* Part B1 and B2: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated)
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography, DRUG: FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Refractory Primary Malignant Central Nervous System Neoplasm, Bones and Joints, Brain and Nervous System, Lymphoma
Children’s Health
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)
FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
All
6 Months to 25 Years old
Phase 2
NCT04775485
STU-2022-0878
Inclusion Criteria:
• Age 6 months to 25 years with:
• Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration
• Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion
• Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration
• Must have received at least one line of systemic therapy and have evidence of radiographic progression
• Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
Exclusion Criteria:
• Patient's tumor has additional previously-known activating molecular alterations
• Patient has symptoms of clinical progression in the absence of radiographic progression
• Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
• Other inclusion/exclusion criteria as stipulated by protocol may apply
Drug: DAY101
Low-grade Glioma, Advanced Solid Tumor, Brain and Nervous System
Children’s Health
A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling
This is a Phase 1/2, multicenter, open-label trial of avapritinib in participants 2 to < 18 years of age with advanced relapsed/refractory (R/R) solid tumors, including central nervous system (CNS) tumors, that harbor a PDGFRA and/or KIT mutation (including non-synonymous point mutations, insertions, and deletions) or amplification, or DMG-H3K27a who have no available curative treatment options. This is a single-arm trial in which all participants will receive avapritinib. The study consists of 2 parts: dose confirmation, safety, and PK (Part 1) and initial efficacy, safety, and PK at the Part 2 recommended dose (Part 2).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
All
2 Years to 17 Years old
Phase 1/Phase 2
NCT04773782
STU-2021-0904
Inclusion Criteria
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
Drug: avapritinib
Solid Tumor, Unspecified, Child, Relapsed Solid Neoplasm, CNS Tumor, Brain and Nervous System, Sarcoma
KIT, PDGFRA, Relapsed/Refractory Solid Tumor, Glioma, H3K27M, DMG-H3K27a
Children’s Health
A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT04777994
STU-2023-0762
Inclusion Criteria:
* Must weigh at least 35 kilograms (kg).
* An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Life expectancy of ≥ 12 weeks.
* Laboratory values meeting protocol criteria.
* QT interval corrected for heart rate \< 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
* Measurable disease defined by RECIST 1.1 criteria.
For Monotherapy and Combination Dose Escalation:
• Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.
For Monotherapy Dose Expansion only:
* Subjects must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
* Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
* Relapsed/refractory HNSCC
* Relapsed/refractory NSCLC
* Advanced ccRCC
For PD-1 Targeting Agent Combination Dose Expansion only:
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
* Relapsed HNSCC
* Relapsed NSCLC
* Relapsed Advanced ccRCC
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
* Locally Advanced or metastatic MSI-H tumors
For VEGFR TKI Combination Dose Expansion only:
* Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
* Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Subjects with poorly controlled hypertension are excluded
Exclusion Criteria:
* Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
* Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
* Unresolved Grade 2 or higher peripheral neuropathy.
* History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
* Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
* Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
* History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
* History of uncontrolled, clinically significant endocrinopathy.
* Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
* If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
* Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
* History of solid organ transplant or allogeneic stem cell transplant.
* History of other malignancy, with the following exceptions:
* No known active disease present within ≥ 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* History of interstitial lung disease or pneumonitis.
* Major surgery ≤ 28 days prior to first dose of study drug
* Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices. DRUG: ABBV-CLS-484, DRUG: Programmed Cell Death-1 (PD-1) Inhibitor, DRUG: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Advanced Solid Tumor Cancer, Cervix, Colon, Kidney, Lung/Thoracic, Ovary
Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
UT Southwestern