UTSW - Study Finder

A Study to Assess How Well and Safely Elafibranor Works in Adult Participants With Primary Sclerosing Cholangitis (ELASCOPE)

Description:

The purpose of this study is to find out how well and safely elafibranor works compared to placebo in adult participants with Primary sclerosing cholangitis (PSC). PSC is a rare disease that causes inflammation and scarring of the bile ducts in the liver. Over time, this can lead to liver damage and serious health problems, including the need for a liver transplant and death. In this study, about 350 participants with large duct PSC will take part. Participants will be randomized to receive either elafibranor 120 mg once daily or a placebo (a tablet with no active medicine). The study includes a screening period, an treatment period, and a post-treatment safety follow-up. During the study, participants will undergo routine clinical assessments, laboratory testing, imaging evaluations, and complete patient-reassessments to evaluate liver disease progression, symptoms, quality of life and safety. Following the end of treatment, participants will complete a safety follow-up period at approximately four weeks. Participants may withdraw from the study at any time. Each participant may be in the study for several years, as the treatment period will continue until the study reaches enough health events among participants, which is expected to take about 5 years.

Contact(s):

studyfinder@utsouthwestern.edu

Principal Investigator:

Gender: ALL

Age: 18 Years to 75 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07387549

Show full eligibility criteria

Inclusion Criteria:

* Adults participants aged 18 years or older * Confirmed diagnosis of primary sclerosing cholangitis based on standard clinical, biochemical, and imaging criteria * Compensated liver disease at screening * Stable background therapy, where applicable prior to study entry * Women of childbearing potential have to apply during the entire duration of the study a highly effective method of birth control * Ability to provide written informed consent and comply with study procedures.

Exclusion Criteria:

\- History or presence of other concomitant chronic liver disease \- History of hepatic decompensation, including: i) History of liver transplantation, current MELD 3.0 score ≥12 due to hepatic impairment. ii) Evidence of complications of cirrhosis * Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child Pugh score. * History of biliary intervention within 60 days prior to the screening period, and/or presence of percutaneous drain or bile duct stent at SV. * History of bacterial cholangitis, and/or participant on antibiotics for prophylaxis of recurrent cholangitis within 60 days prior to the SV. * History or any current suspicion of cholangiocarcinoma or hepatocellular carcinoma * Known malignancy or history of malignancy within the last 5 years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix. * Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease). * Administration of the following medications are prohibited as specified below: i) 3 months prior to baseline: norucholic acid, fibrates, seladelpar and glitazones. ii) 3 months prior to baseline: cyclosporine, mycophenolate, pentoxifylline, and chronic systemic corticosteroids (except as part of management of IBD at an ongoing stable dose); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin). * Participants who are currently participating in, plan to participate in, or have participated in an investigational drug or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to the SV. - Participants with previous exposure to elafibranor. * Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) \>450 msec in males or QTcF \>470 msec in females for participants without bundle branch block. * Significant renal disease, * For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating. * Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women * History of alcohol abuse, or other substance abuse within 1 year prior to SV. * Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study. * Mental instability or incompetence * Participant has or is known to have tested positive for human immunodeficiency virus (HIV) type 1 or 2 at SV. * Medical conditions that may diminish life expectancy to \<2 years.

Interventions: DRUG: Elafibranor, OTHER: Placebo

Conditions: Primary Sclerosing Cholangitis

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (Beacon-BTC)

Description:

This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Hsieh

Gender: ALL

Age: 18 Years to old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07265674

IRB Number: STU20252028

Show full eligibility criteria

Inclusion Criteria:

\- Individuals are eligible to be included in the study only if all of the following criteria apply:
• At least 18 years of age inclusive at the time of signing the informed consent.
• Provides informed written consent according to local laws or regulations.
• Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study.
• Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial.
• Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit.
• Histologic or cytologic diagnosis of BTC.
• Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI).
• Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L1.
• Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen.
• If a patient has a mutation/fusion of IDH1, FGFR2 or NTRK, or an amplified, mutated, or overexpressed form of HER2, or a recognized aberration in a validated "driver" of BTC, and was treated with an appropriate targeted agent, or the patient's tumor was determined to be MSI-H and an appropriate PD-1/PD-L1 mAb was administered, the targeted therapy or immunotherapy will NOT count as a separate line of treatment.
• ECOG PS of 0 or 1.
• Expected life expectancy of at least 90 days after the first day of treatment as per the site Investigator.
• At least 1 measurable lesion by RECIST v1.1 based on imaging (eg, CT, MRI) performed within 28 days prior to initiation of study intervention. Those who have received prior local therapy, including but not limited to embolization, chemoembolization, radiation therapy, and/or other appropriate ablative procedures to a measurable lesion that is within the treatment and shown ≥ 20% growth in size since posttreatment assessment.
• Resolution to ≤ Grade 1 by the NCI CTCAE v 5.0 (or higher) of all clinically significant toxic effects of prior chemotherapy or other treatments, except for alopecia and peripheral neuropathy (these must have resolved to ≤ Grade 2). If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.
• Adequate hematologic function:
• ANC ≥ 1.5 × 109/L. Myeloid growth factors must not have been administered within 7 days before the participant's first dose of study intervention.
• Hemoglobin ≥ 8.5 g/dL and no RBC transfusions during the 14 days before the participant's first dose of study intervention.
• Platelet count ≥ 100 × 109/L and no platelet transfusions during the 14 days before the participant's first dose of study intervention.
• Adequate baseline organ function, as demonstrated by the following:
• eGFR ≥ 50 mL/min as estimated by CKD-EPI 2021.
• Bilirubin ≤ 2 × ULN (local institution).
• AST and ALT ≤ 5 × ULN (local institution).
• Adequate coagulation function as defined by INR ≤ 1.5 OR a PT ≤ 1.5 × ULN AND an aPTT ≤ 1.5 × ULN if not receiving anticoagulation therapy. Note: Participants may receive subtherapeutic doses of warfarin while on study to maintain patency of venous devices but not with therapeutic doses of warfarin. Participants may be treated with low-molecular weight heparin.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and study follow up or for at least 9 months after the last dose of study intervention. Note: A woman is of nonchildbearing potential if she meets 1 of the following criteria: a) postmenopausal with at least 12 months of spontaneous amenorrhea; b) has had a bilateral oophorectomy; or c) has had a hysterectomy. Highly effective methods of contraception include: * Abstinence from sexual activity. * Hormonal contraception (eg, injection, implant, pill, patch, or vaginal ring as available in each country) associated with inhibition of ovulation (both estrogen and progestogen and progestogen only) in use for at least 30 days before administration of study intervention. * Intrauterine device in use for at least 30 days before administration of study intervention. * Intrauterine hormone-releasing system in use for at least 30 days before administration of study intervention. * Bilateral tubal occlusion/ligation at least 6 months before administration of study intervention. * Partner who has been vasectomized at least 6 months before administration of study intervention.
• Males and their female partners must use a highly effective method of birth control if female partner(s) is of childbearing potential, and males must not donate sperm during the study and for 9 months after the last dose of study intervention.

Exclusion Criteria:

* Individuals will be excluded from study participation if they meet any of the following criteria:
• Received systemic therapy or an investigational agent before washing out, as follows:
• \< 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy
• \< 3 weeks prior to Cycle 1 Day 1 for immune-based therapy
• ≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent
• Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day 1. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease.
• Underwent hepatic radiation, chemoembolization, or radiofrequency ablation \< 4 weeks prior to Cycle 1 Day 1.
• Underwent major surgery \< 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement.
• Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Resting QTcF \> 470 msec at screening.
• An additional active malignancy that is progressing or has required active treatment within the past 3 years. Cases involving a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, breast cancer, and melanoma in situ), organ-confined prostate cancer with no evidence of PD.
• Require strong inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OATP1A2, and OAT3 transporters unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Require sensitive substrates of OATP1B1 and OATP1B3 unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Known positive status for HIV, has not been treated with established appropriate antiretroviral therapy for at least 4 weeks, and has a hydrophobic interaction chromatography viral load \< 400 copies/mL and a CD4+ T-cell (CD4+) counts ≥ 350 cells/µL prior to enrollment. No HIV testing is required unless mandated by local health authority.
• Active or chronic HBV and active (not cured) HCV. Participants who are HBV carriers without active disease (HBV DNA titer \< 1000 copies/mL or 200 IU/mL) or cured HCV (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
• An uncontrolled intercurrent illness including, but not limited to medical illness; uncontrolled infection requiring therapy; psychiatric illness; alcohol or drug dependence; social situations or a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator or Medical Monitor.
• Requires therapeutic doses of warfarin (ie, requires monitoring). A washout period of 7 days before administration of a participant's first dose of study intervention is required for those in whom therapeutic doses of warfarin are discontinued. Note: Warfarin at a low daily dose to maintain patency for indwelling venous catheters is allowed. Low-molecular weight heparin and direct-acting oral anticoagulants, according to the inclusion requirements pertaining to coagulation test results, are allowed.
• Clinically significant edema or intracavitary fluid collections (eg, ascites, pleural effusion, pericardial effusions) resulting in moderate symptoms and/or requiring frequent drainage.
• Previously developed shock, anaphylaxis, or renal disorder due to SBECD.
• WOCBP who is pregnant, lactating, or discontinued lactation \< 12 weeks prior to Screening, or who plans to become pregnant or initiate lactation during the study.
• Known reaction or contraindication to any component of study intervention (ie, oxaliplatin, leucovorin \[including levoleucovorin\], and 5-FU \[FOLFOX\] and irinotecan, leucovorin, and 5-FU \[FOLFIRI\]).
• Known DPD deficiency. Screening for DPD deficiency is not mandated but should be considered in subjects who have had severe toxicity due to fluoropyrimidine-based therapy in the past.

Interventions: DRUG: Nanvuranlat, OTHER: Physician's Best Choice

Conditions: Advanced Biliary Tract Cancer, Biliary Tract Cancer (BTC)

Keywords: Intrahepatic cholangiocarcinoma (IHC), Extrahepatic cholangiocarcinoma (EHC), Gallbladder carcinoma (GBC)

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Evaluation of Liver Stiffness Performance, by FibroScan®, to Detect Elevated Central Venous Pressure (CVP)

Description:

This is a pivotal, global, prospective, cross-sectional, multicentric clinical investigation designed to explore a non-invasive, reliable alternative to invasive, catheter-based hemodynamic assessments, which are associated with procedural risks and limited applicability in certain participant populations.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Serrano@UTSouthwestern.edu

Principal Investigator: Ambarish Pandey

Gender: ALL

Age: 18 Years to old

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07222813

IRB Number: STU20251935

Show full eligibility criteria

Interventions: DEVICE: FibroScan, PROCEDURE: Right-sided Heart Catheterization, PROCEDURE: Transthoracic echocardiography, BIOLOGICAL: Blood Sample Analysis

Conditions: Heart Failure, Heart Failure - NYHA II - IV

Keywords: Fibroscan, Vibration Control Transient Elastography, Liver Stiffness Measurement, Guided VCTE

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study to Assess Adverse Events and Change in Disease Activity in Participants 12 Years of Age or Older With Locally Advanced or Metastatic Solid Tumors That Harbor MET Amplification Receiving Intravenously Infused Telisotuzumab Adizutecan

Description:

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity of telisotuzumab adizutecan. Telisotuzumab adizutecan is an investigational drug being developed for the treatment of locally advanced or metastatic solid tumors that harbor MET amplification. This study will have 1 arm where participants will receive telisotuzumab adizutecan. Approximately 100 participants 12 years of age or older. with solid tumors harboring MET amplification will be enrolled in the study in up to 50 sites around the world. Participants will receive intravenous (IV) telisotuzumab adizutecan, as part of the 61.5 month study duration. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Syed Kazmi

Gender: ALL

Age: 12 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07196644

IRB Number: STU20251978

Show full eligibility criteria

Interventions: DRUG: Telisotuzumab Adizutecan

Conditions: Solid Tumors Harboring MET Amplification, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Gall Bladder, 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

Keywords: Solid Tumors harboring MET Amplification, Telisotuzumab Adizutecan

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Personalized Radiotherapy for Individualized Treatment Strategies and Monitoring (PRISM) (PRISM)

Description:

To characterize feasibility, safety, and/or preliminary efficacy of personalized strategies to adapt standard radiotherapy treatments to individual patient responses.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Neil Desai

Gender: ALL

Age: 18 Years to old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07139990

IRB Number: STU20251050

Show full eligibility criteria

Inclusion Criteria:

Cohort A: * \>=18 years old * Performance status ECOG 0-2 * Extensive stage small cell lung cancer diagnosed by tissue biopsy within 180 days of registration. * Patient must be planned for or receiving standard of care chemoimmunotherapy. * Patient must have received no more than 3 cycles by time of study enrollment. * Able and indicated according to investigator to receive thoracic radiotherapy Cohort B: * 18 years old * Diagnosis of solid tumor malignancy with MRI-defined brain metastasis lesions within 60 days of registration * Each brain metastasis lesion enrolled must be 2 - 5 cm, except brainstem lesions which may be 1.5 - 5cm in size. Cohort C: * \>=18 years old * Performance status ECOG 0-2 * Histologically confirmed surgically resectable, high grade (FNCLCC grade 2 or 3), localized soft tissue sarcoma of the trunk or extremities that measures \>5 cm in any direction as assessed by imaging * Eligible to receive immunotherapy Cohort D: * \>=18 years old * Performance status ECOG 0-2 * Pathologically proven diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx * Clinical stage III/IVA (AJCC 8th edition) * Disease must be deemed resectable by head and neck surgeon * Eligible to receive immunotherapy

Exclusion Criteria:

Cohort A: ⨀ Prior thoracic Radiotherapy Cohort B: * Prior whole brain Radiotherapy * Prior surgical resection or focal radiotherapy of a target brain metastasis * Leptomeningeal disease Cohort C: * Unresectable or metastatic (nodal or distant) disease * Synchronous malignancy requiring chemotherapy or other intensive treatment * Locally recurrent soft tissue sarcoma * Prior immunotherapy * Pregnancy or breastfeeding Cohort D: * Distant metastasis * Inability to undergo PET-CT for baseline staging * HPV-positive or p16-positive oropharyngeal cancer * Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable * Prior immunotherapy for the study cancer or for a remote cancer * Prior head and neck radiotherapy

Interventions: RADIATION: Cohort A: Extensive Stage Small Cell Lung Cancer (ES-SCLC) Thoracic Tumor PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy), RADIATION: Cohort B: Brain metastasis PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy), RADIATION: Cohort C: Sarcoma Pre-Operative PULSAR, RADIATION: Cohort D: Resectable Head & Neck Squamous Cell Carcinoma (HNSCC) PULSAR/SAbR

Conditions: Small Cell Lung Cancer Extensive Stage, Brain Metastases, Solid Tumor, Adult, Thoracic Cancer, Sarcoma,Soft Tissue, HNPCC, Multiple

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors

Description:

The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include: * What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET * What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Nisha Unni

Gender: ALL

Age: 18 Years to old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07029399

IRB Number: STU20251544

Show full eligibility criteria

Interventions: DRUG: NKT5097 CDK2/CDK4 dual degrader, DRUG: Fulvestrant, DRUG: Letrozole

Conditions: HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Liver, Lung/Thoracic, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Ovary, Pancreas, Prostate, Small Intestine, Stomach, Urinary Bladder, Uterine (Endometrial)

Keywords: CCNE1, cyclin E1, triple negative breast cancer, TNBC, estrogen receptor positive, HER2-, breast cancer, post CDK4/6i, HER2 expression, Fulvestrant, Letrozole, endocrine therapy, refractory, endocrine resistant, endocrine sensitivity, metastatic

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)

Description:

The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting. ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows: * Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open. * Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Heather McArthur

Gender: ALL

Age: 18 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT07007559

IRB Number: STU20251383

Show full eligibility criteria

Inclusion Criteria:

* Histologically confirmed invasive HER2+ breast cancer based on an evaluable tumor tissue biopsy obtained after cessation of T-DXd (ENHERTU) treatment and no more than 6 months prior to C1D1. * Received no more than 4 prior lines of HER2-directed therapy including at least one prior line of T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible. * Progressed on or following the most recent line of therapy. * Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine). * Measurable disease as defined by RECIST v1.1. * LVEF ≥50%. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1. * Life expectancy of at least 3 months. * Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. * Adequate liver function: * Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome); * Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease). * Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.

Exclusion Criteria:

* Untreated CNS metastases. * Prior exposure to any anti-CD47 or anti-SIRPα agent. * Any condition that would be contraindicated to receiving trastuzumab * Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen * Following anti-cancer therapy with insufficient washout before start of treatment:
• chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
• Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment). * History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction. * Had an allogeneic tissue/solid organ transplant. * Any active, unstable cardiovascular disease. * Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients). * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Other primary malignancy within 2 years.

Interventions: DRUG: Evorpacept (ALX148), DRUG: Trastuzumab, DRUG: Paclitaxel, DRUG: Capecitabine, DRUG: Eribulin, DRUG: Gemcitabine, DRUG: Vinorelbine

Conditions: Breast Cancer, Metastatic, Breast - Female, Breast - Male

Keywords: metastatic, Her2+, metastatic HER2-positive breast cancer, breast cancer, HER2-positive, Evorpacept, CD47, ERBB2, Enhertu, trastuzumab deruxtecan, ASPEN-09, Herceptin, solid tumors, trastuzumab, ALX148, mBC, ASPEN-Breast

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Breast Cancer w/Liver Dominant Disease (DELUMA)

Description:

The goal of this clinical trial is to learn if using a liver-directed therapy with high dose chemotherapy followed by approved cancer treatment to treat patients with breast cancer that has spread to the liver is safe and tolerable. The clinical trial will also learn if the liver-directed therapy with high dose chemotherapy works on the disease in the liver. Investigators will compare the use of the liver-directed therapy with high dose chemotherapy followed by approved cancer treatment or approved cancer treatment alone. Participants will: * Undergo up to two cycles of liver-directed therapy with high dose chemotherapy procedures followed by approved cancer treatment or take approved cancer treatment alone * Visit clinic at least every two weeks for checkups and tests * Complete scans approximately every 8 weeks

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Heather McArthur

Gender: ALL

Age: 18 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06875128

IRB Number: STU20252128

Show full eligibility criteria

Inclusion Criteria:

* Histologically confirmed diagnosis of MBC. * Patients with HER2-negative (IHC 0 or 1+ or 2+ and ISH non-amplified) MBC (including triple negative disease). * Patient with Hormone Receptor-Positive disease has progressed on or intolerant of prior endocrine therapy and CDK 4/6 inhibitors. * Disease progression after TOPO-1 isomerase inhibitor payload ADC, such as sacituzumab govitecan and/or trastuzumab deruxtecan. Patients not eligible or suitable for ADCs can be considered for this study. NOTE: In jurisdictions where those ADCs are not available as standard of care, patients will be eligible after prior treatment or intolerable toxicity on two standard chemotherapy regimens for the appropriate disease subtype. * Patient with HER2-negative breast cancer suitable for single agent chemotherapy as per judgement of treating investigator. * Patient is a suitable candidate for treatment with one of the following: eribulin, vinorelbine, or capecitabine as per judgement of treating investigator. * Patient has liver dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and/or the life-threatening component of the disease is located in the liver. * MBC metastases must involve ≤ 50% of the liver parenchyma. * If there is evidence of extrahepatic metastatic disease, it is limited, and the life-threatening component of disease is in the liver. Extrahepatic disease is restricted to lesions in the breast, lung, other visceral organs, lymph nodes and skin. * Disease in the liver must be measurable (per RECIST v1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI). * Patient weighs ≥ 35 kg * Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to randomization. * Patient has an ECOG PS of 0-1.

Exclusion Criteria:

* Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy. * Evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy). * New York Heart Association functional classification II, III or IV or active cardiac condition(s), including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease that create(s) undue risks of undergoing general anesthesia. * History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia. * History of bleeding disorders, presence of brain metastases or other intracranial abnormalities that would put them at risk for bleeding with anti-coagulation. * Known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis. * An active second malignancy or has a history of recent definitively treated invasive cancer within 2 years prior to enrolment. Exceptions are optimally treated and controlled basal cell carcinoma, other skin cancers, thyroid cancer. * Symptoms and signs indicating clinically significant progression of disease including cord compression, increasing pain symptoms, increasing oxygen requirements, impending pathological fracture, compressive lymphadenopathy, or symptomatic pleural effusion. * Pregnant or breastfeeding. * WOCBP (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) who is unable to undergo hormonal suppression to avoid menstruation during treatment. * Patient requires chronic use of immunosuppressive drugs. NOTE: Oral prednisolone ≤ 10 mg/day or equivalent is allowed. * Unable to be temporarily removed from chronic anti-coagulation therapy. * Active bacterial infections with systemic manifestations (malaise, fever, leucocytosis). * An active infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s). * Known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids. * History of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system. * Known latex allergy. * History of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia. * Uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism. * Received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization. * Patients should have recovered to Grade 1 or less for AEs related to prior treatment unless deemed clinically not significant, such as lymphopenia, anemia, or grade 2 neuropathy due to prior taxane treatment. NOTE: Certain side effects that are unlikely to develop into serious or life-threatening events (e.g., alopecia) are allowed at ≥ Grade 1. * \< 28 days after surgery and surgical wound is not fully healed. * Currently under treatment for cancer other than MBC or is not deemed to be cancer free. * Not eligible to receive either eribulin or vinorelbine or capecitabine. * Albumin level \< 3.0 g/dL.

Interventions: DRUG: Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine), DRUG: Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Conditions: Metastatic Breast Cancer in the Liver, Breast - Female, Breast - Male

Keywords: melphalan, melphalan/HDS, melphalan/hepatic delivery system, eribulin, vinorelbine, capecitabine, metastatic breast cancer, MBC, liver dominant disease, metastatic breast cancer in the liver, hepatic delivery system, PHP, HER2-negative breast cancer, HER-2 negative, Hormone Receptor-Positive disease

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Ligufalimab and Cadonilimab in Advanced Liver Cancers

Description:

The goal of this clinical trial is to find out if the combination of Ligufalimab and Cadonilimab are effective in treating advanced hepatobiliary cancers that have failed prior therapy.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Hsieh

Gender: ALL

Age: 18 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06789848

IRB Number: STU-2024-1210

Show full eligibility criteria

Inclusion Criteria:

• Histological confirmation of specific disease -Cohort A (HCC): Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC will be excluded. * Cohort B (BTC, biliary tract cancers): Patients must have histologically confirmed biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers). Patients with combined HCC-cholangiocarcinoma may be enrolled in Cohort B.
• Locally advanced or metastatic disease * 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. * Measurable disease, as defined as lesions that can accurately be measured in at least 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 a high-grade toxicity (Grade 4) are not eligible.
• For patients in cohort A who do not have a clinical diagnosis of HCC according to the AASLD criteria, formalin-fixed, paraffin-embedded (FFPE) tumor diagnostic tissue samples must have been obtained within 4 years from the time of consent. Baseline tissue will be requested any time after consent. It is strongly recommended that tissue is obtained from standard-of-care 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 therapy 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% since the cessation of locoregional therapy 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 (only applicable 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: -Platelet count ≥ 50,000/mm3 -Hgb ≥ 9 g/dl -Absolute neutrophil ≥ 1,000 cells/mm3 -Total bilirubin ≤ 3 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, or patients with hyperbilirubinemia secondary to distal malignant obstruction where endoscopic, surgical, or percutaneous bypass/stenting has been attempted. Such patients may be enrolled based in consultation with the principal investigator) -INR ≤ 2 -AST, ALT ≤ 5 times ULN * Calculated creatinine clearance (CrCl) ≥ 40 mL/min. CrCl can be calculated using the Cockroft-Gault method. * 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 highly effective contraception methods (hormonal or barrier method of birth control or abstinence) 4 weeks prior to study entry, for the duration of study participation, and for 120 days after the last dose of ligufalimab or cadonilimab. 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). 11\. Women of child-bearing potential must have a negative serum pregnancy test at screening. 12\. 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. 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. 13\. Ability to understand and the willingness to sign a written informed consent. 14\. Willing and able to comply with the requirements and restrictions in this protocol. 15\. 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: * Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying), * Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs, * Clinically significant cardiovascular disease, * A condition that may obscure the interpretation of toxicity determination or AEs, * History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-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. * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * 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.
• Patients who discontinued prior immune checkpoint inhibitor treatment due to Grade ≥ 3 or Grade 2 serious toxicity (i.e., pneumonitis, uveitis, neurological symptoms, cardiac toxicity, etc.) immune-related adverse events.
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Prior malignancy that required systemic treatment 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.

Interventions: DRUG: Ligufalimab, DRUG: Cadonilimab

Conditions: Advanced Hepatocellular Carcinoma, Refractory Hepatocellular Carcinoma, Biliary Tract Cancer, Liver, Other Digestive Organ

Keywords: liver, other digestive organs

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Lead-212 PSV359 Therapy for Patients With Solid Tumors

Description:

Phase I/IIa image-guided, alpha-particle therapy study of \[203Pb\]Pb-PSV359 and \[212Pb\]Pb-PSV359 in patients with solid tumors that are known to be Fibroblast Activation Protein (FAP)-positive.

Contact(s):

studyfinder@utsouthwestern.edu

Principal Investigator:

Gender: ALL

Age: 18 Years to 90 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06710756

Show full eligibility criteria

Interventions: DRUG: [203Pb]Pb-PSV359, DRUG: [212Pb]Pb-PSV359

Conditions: Pancreatic Ductal Adenocarcinoma, Gastric Cancer, Esophageal Cancer, Colorectal Cancer, Ovarian Cancer, Head and Neck Cancer, Sarcoma, Mesothelioma

Keywords: Fibroblast Activation Protein, Solid tumor malignancy, Gastric cancer, Esophageal cancer, Colorectal cancer, Ovarian cancer, Head and neck cancer, Theronostic, Radiopharmaceutical, Radiotherapy, Alpha Particle, Pb-203, Pb-212

I'm interested

Share via email

See this study on ClinicalTrials.gov

Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

Description:

First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Nisha Unni

Gender: ALL

Age: 18 Years to old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06625775

IRB Number: STU20250194

Show full eligibility criteria

Inclusion Criteria:

* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC) * Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 * Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only) * Stable brain metastases * Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC) * Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy * BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i * BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted * BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required

Exclusion Criteria:

* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors * Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2) * Patients with untreated and/or non-stable brain metastases Other inclusion/exclusion criteria are specified in the protocol

Interventions: DRUG: BBO-10203, DRUG: Trastuzumab, DRUG: Fulvestrant, DRUG: Ribociclib, DRUG: FOLFOX, DRUG: Bevacizumab

Conditions: Solid Tumor, Adult, Metastatic Breast Cancer, Advanced Breast Cancer, HER2 Mutation-Related Tumors, HER2-positive Metastatic Breast Cancer, KRAS Mutant Metastatic Colorectal Cancer, Metastatic Lung Cancer, Metastatic Colorectal Cancer, Advanced Lung Cancer, HR-positive, HER2-negative Advanced Breast Cancer, HER2-positive Advanced Breast Cancer

Keywords: BREAKER-101, BridgeBio Oncology Therapeutics, BBOT, Phase1, Phase 1a/1b, Trastuzumab, Breast, Colorectal, Non-Small Cell Lung Cancer, CRC, NSCLC, Metastatic Cancer, Advanced Cancer, HER2-positive, HR-positive, HR-positive, HER2-negative, HER2-negative

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

Description:

The goal of the Monotherapy Dose Escalation phase (Part 1) of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Monotherapy Expansion phase of the study (Part 2) is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D). The goal of the Combination Dose Escalation phase (Part 3) of the study is to identify the RDE of NKT3964 in combination with chemotherapy in adult subjects with advanced/metastatic endometrial cancer. The goal of the Combination Expansion phase of the study (Part 4) is to evaluate the preliminary anti-tumor activity of NKT3964 in combination with chemotherapy at the RDE based on ORR.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Miller

Gender: ALL

Age: 19 Years to old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06586957

IRB Number: STU20252305

Show full eligibility criteria

Inclusion Criteria:

\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 Monotherapy Dose Escalation (including Food Effect Sub-study): subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. Part 1 Monotherapy Dose Escalation:
• Ovarian cancer
• Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
• Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
• Small cell lung cancer (SCLC)
• Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
• HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy \[ET\])
• Other solid tumors with CCNE1 amplification * \- Part 2 Monotherapy Dose Expansion: * Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate \[ADC\]) in the metastatic setting.. * Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification. * Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification. * Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification. Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor. * Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug. * -Part 3 Combination Dose Escalation: * Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification. (Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor) * -Part 4 Combination Dose Expansion: * Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification. (Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor) * Have adequate organ function * Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception * Ability to swallow oral medications. * Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment

Exclusion Criteria:

* Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy. * History of another malignancy with exceptions * History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis. * Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE) * Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment * Known active CNS metastases and/or carcinomatous meningitis * Active interstitial lung disease currently requiring treatment * History of uveitis, retinopathy or other clinically significant retinal disease * Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease * Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964. * Known human immunodeficiency virus (HIV), active hepatitis B or C infection * Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader * Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder * Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1 * Prior severe hypersensitivity reaction to paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil (Cohort 3A and 4A only) or severe hypersensitivity reaction to doxorubicin or any other component of the product, other anthracyclines or anthracenediones (Cohort 3B and 4B). * \- For subjects in Cohort 3B or 4B only: * Left ventricular ejection fraction (LVEF) \<50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 4 weeks prior to first dose * Active cardiac conditions including myocarditis, pericarditis, or clinically significant valvular heart disease * Known elevated cardiac biomarkers at baseline * History of anthracycline-related cardiomyopathy regardless of recovery * Cumulative lifetime exposure to doxorubicin, including planned doxorubicin in Part 3b or Part 4b, exceeding 450 mg/m2

Interventions: DRUG: NKT3964, DRUG: Paclitaxel, DRUG: Doxorubicin

Conditions: Solid Tumor, Advanced Solid Tumor, Solid Tumor, Adult, Metastatic Tumor, Ovarian Cancer, Ovarian Neoplasms, Ovarian Carcinoma, Metastatic Ovarian Carcinoma, Endometrial Neoplasms, Endometrial Diseases, Metastatic Endometrial Cancer, Triple Negative Breast Cancer, Metastatic Endometrial Carcinoma, Advanced Endometrial Carcinoma, Advanced Ovarian Carcinoma, Gastric Cancer, Advanced Gastric Carcinoma, Metastatic Gastric Cancer, Metastatic Gastric Carcinoma, Small Cell Lung Cancer, Small Cell Lung Carcinoma, Triple Negative Breast Neoplasms, Platinum-resistant Ovarian Cancer, Platinum-Refractory Ovarian Carcinoma, CCNE1 Amplification, Hormone Receptor Negative Breast Carcinoma, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Progesterone-receptor-positive Breast Cancer

Keywords: CDK 2 Inhibitor, CDK 4 Inhibitor, CDK 6 Inhibitor, CDK2 Degrader, Protein Degrader, PROTAC

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010)

Description:

The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer. The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Heather McArthur

Gender: ALL

Age: 18 Years to old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06312176

IRB Number: STU-2024-0526

Show full eligibility criteria

Interventions: DRUG: Sacituzumab tirumotecan, BIOLOGICAL: Pembrolizumab, DRUG: Paclitaxel, DRUG: Nab-paclitaxel, DRUG: Capecitabine, DRUG: Liposomal doxorubicin

Conditions: Breast Neoplasms

Keywords: Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

Description:

The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Hsieh

Gender: ALL

Age: 18 Years to old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06282575

IRB Number: STU-2024-0655

Show full eligibility criteria

Inclusion Criteria
• Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
• Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
• Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
• HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
• Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
• Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Females of childbearing potential must have a negative pregnancy test result.
• Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control. Exclusion Criteria
• Prior treatment with a HER2-targeted agent
• Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
• The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
• Use of systemic corticosteroids.
• Brain metastases
• Severe chronic or active infections
• History of allogeneic organ transplantation.
• Active or prior autoimmune inflammatory conditions
• History of interstitial lung disease or non-infectious pneumonitis.
• Participation in another clinical trial with an investigational medicinal product within the last 3 months.
• Females who are breastfeeding
• Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
• Use of phenytoin

Interventions: DRUG: Zanidatamab, DRUG: Cisplatin, DRUG: Gemcitabine, DRUG: Pembrolizumab, DRUG: Durvalumab

Conditions: Biliary Tract Cancer, Other Digestive Organ

Keywords: JZP598, ZW25, HER-2 positive BIliary Tract cancer, Gallbladder Cancer, Intrahepatic Cholangiocarcinoma (ICC), Extrahepatic Cholangiocarcinoma (ECC), Zanidatamab, HER-2 overexpression, HER-2 amplification

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

CEUS vs. AMRI for HCC Detection in Patients With Indeterminate Liver Nodules

Description:

The study will be conducted at the following locations: 1. UT Southwestern Medical Center 2. Parkland Health and Hospital System 3. University of Michigan Investigators will prospectively compare the performance of dynamic contrast enhanced abbreviated MRI (AMRI) and contrast-enhanced ultrasound for early-stage HCC detection in patients with indeterminate liver nodules.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Amit Singal

Gender: ALL

Age: 18 Years and over

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06184152

IRB Number: STU-2023-0230

Show full eligibility criteria

Interventions: DIAGNOSTIC_TEST: CEUS imaging, DIAGNOSTIC_TEST: aMRI imaging

Conditions: HCC, Hepatocellular Carcinoma, Liver

Keywords: LR3, LR4, HCC Surveillance

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

Description:

This phase II ComboMATCH treatment trial compares the effect of neratinib to the combination of neratinib and palbociclib in treating patients with HER2 positive solid tumors. Neratinib and palbociclib are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving neratinib and palbociclib in combination may shrink or stabilize cancers that over-express a specific biomarker called HER2.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: James Wilder

Gender: ALL

Age: 18 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06126276

IRB Number: STU20251154

Show full eligibility criteria

Inclusion Criteria:

* Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N5 based on the presence of an actionable mutation as defined in EAY191 * Patients must have a HER2 amplified solid tumor except breast cancer. * If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of in situ hybridization (ISH)/FISH or next generation sequencing (NGS) status * If IHC is 3+, pt IS ELIGIBLE regardless of ISH/FISH or NGS status * If IHC is 2+, ISH/FISH OR NGS must be positive for the patient to be ELIGIBLE. Otherwise, pt is NOT ELIGIBLE * If IHC is unknown and… * ISH/FISH is positive, independent of NGS results, the patient IS ELIGIBLE * ISH/FISH is negative and NGS positive with ≥ 7 copies, the patient IS ELIGIBLE * Patients must have recurrent or persistent disease * No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation * Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191) * Patients must have measurable disease based on RECIST 1.1. A second measurable lesion outside of the biopsiable lesion is required * Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression for 3 months or more and patient is not on steroids and is asymptomatic * No known leptomeningeal disease * Patients may have received up to 5 prior lines of systemic therapy * Prior therapy with trastuzumab or pertuzumab, either alone or in combination, antibody drug conjugates (ADC) such as DS8201a or T-DM1 is allowed * No prior therapy with HER2 targeting tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib * No prior therapy with CDK4/6 inhibition * No cancer directed therapy within 3 weeks prior to registration. For oral therapy, the washout can be reduced to greater than or equal to 5 half lives of the drug. No HER2 targeting ADCs within 30 days prior to registration * Age ≥ 18 * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 * Not pregnant and not nursing * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3 * Platelets ≥ 100,000 cells/mm\^3 * Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 9 g/dl is acceptable) * Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula * Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN) * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * No active infection requiring parenteral antibiotics * No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube * No current evidence of malabsorption or chronic diarrhea or any other significant gastro-intestinal disease (e.g gastrectomy, ileal bypass, Crohn's disease, gastroparesis), associated with moderate to severe diarrhea (grade 2 or more) or inability to tolerate oral therapy * No lung disease causing dyspnea at rest * No interstitial lung disease with ongoing signs and symptoms at the time of registration * No history of allergic reaction to the study agents, compound of similar chemical or biologic composition of the study agents or any of their excipients

Interventions: PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, DRUG: Neratinib Maleate, DRUG: Palbociclib

Conditions: Malignant Female Reproductive System Neoplasm, Malignant Solid Neoplasm, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

National Liver Cancer Screening Trial (TRACER)

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Amit Singal

Gender: ALL

Age: 18 Years to 85 Years old

Phase: PHASE4

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06084234

IRB Number: STU-2023-0842

Show full eligibility criteria

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

Interventions: DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP

Conditions: Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B, Liver

Keywords: Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (COLT)

Description:

This is a multi-center clinical trial in Cytomegalovirus (CMV) seronegative prospective liver transplant recipients to determine the efficacy of two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine pre-transplant. The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days post-Tx in CMV seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients (LTxRs). A protocol-mandated preemptive therapy (PET) will be used for CMV disease prevention in D+R- LTxRs.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Rhoda.AnnohGordon@UTSouthwestern.edu

Principal Investigator: Ricardo La Hoz

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06075745

IRB Number: STU-2024-0595

Show full eligibility criteria

Inclusion Criteria:

• Subject must be able to understand and provide informed consent
• Negative for Cytomegalovirus (CMV) IgG antibody as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory within 12 months of enrollment, and no history of prior positive CMV serology (IgG antibody)
• Negative human immunodeficiency virus (HIV) testing and no clinical suspicion of HIV infection
• Planned for a first living donor liver transplant or listed/anticipated to be listed for a first deceased donor liver transplant.
• Anticipated to receive a liver transplant within 1-12 months
• For individuals of reproductive potential, a negative serum or urine pregnancy test within 72 hours prior to enrollment. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) \>=40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy)
• Participants who are able to impregnate or become pregnant (i.e., of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control (hormonal or barrier method) or agree to not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for at least 1 month following the last vaccine/placebo dose. For acceptable contraception methods that are more than 80 percent effective, see Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol)
• The most recent platelet count is \>= 20,000 cells/mm\^3 within 3 months prior to enrollment and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 at time of study IP administration. Eligibility criteria required: Dose 2:
• Most recent platelet count \>= 20,000 cells/mm\^3 within 3 months prior to enrollment and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 since last result
• For women of reproductive potential as defined previously, a negative serum or urine pregnancy test (performed within 72 hours)

Exclusion Criteria:

• Women who are breastfeeding or planning to breastfeed
• Prior Cytomegalovirus (CMV) vaccination
• Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes coronavirus disease (COVID) convalescent plasma)
• Currently enrolled in another interventional study that, in the investigator's opinion, could affect the evaluation of safety and/or vaccine effect outcomes
• Prior (ever) receipt of a stem cell transplant (Peripheral blood stem cell (PBSC), marrow, cord blood, etc.)
• Receipt of immunosuppression: * Within the last 3 months prior to randomization: * Systemic Chemotherapy or immunotherapy for cancer in the last 3 months (localized therapy for hepatocellular carcinoma \[HCC\] such as chemoembolization, Y-90 are not considered "systemic chemotherapy" and are not excluded) * Systemic immunosuppressive agents (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, mTOR inhibitors, TNF-alpha inhibitors) and/or combination immunosuppressive drugs for any autoimmune or other conditions in the last 3 months except corticosteroids as below * Within the last 28 days prior to randomization: averaged daily corticosteroid therapy dose ≥20 mg of prednisone equivalent * Within the last 6 months prior to randomization: receipt of T- or Bcell depleting agents (e.g. ATG, Alemtuzumab, Rituximab)
• Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next month
• At the time of randomization, either listed for, or, in the opinion of the investigator, likely to receive any non-liver organ transplant
• Receipt of a clinical vaccine \< 14 days before or planned to receive a clinical vaccine \<14 days after the study agent
• Known allergy to any component of the study agent
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study Exclusion criteria required: Dose 2:
• Anaphylaxis or other severe reaction (Grade 4) considered definitely or probably attributable to dose 1
• Receipt of liver transplant prior to dose 2
• The participant must not have any severe acute illness or other factor, that, in the opinion of the investigator, requires postponement of dose 2 because of safety concerns. The participant can be re-evaluated for eligibility throughout the window of eligibility for the dose 2, once the illness or other factor has improved or resolved
• Receipt of a clinical vaccine \< 14 days before or planned to receive a clinical vaccine \<14 days after the study agent

Interventions: DRUG: CMV-MVA Triplex, DRUG: Placebo for CMV-MVA Triplex

Conditions: Liver Transplant

Keywords: Cytomegalovirus, Vaccine, Orthotopic Liver Transplant

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)

Description:

The goal of this clinical study is to learn more about the study drug, seladelpar, and its effects on clinical outcomes in participants with primary biliary cholangitis (PBC) and compensated cirrhosis. The primary objective of this study is to evaluate the effect of seladelpar compared to placebo on EFS. EFS is defined as the time from start of treatment to the first occurrence of any of the following adjudicated events up to Week 156.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Lakeisha.Strachan@UTSouthwestern.edu

Principal Investigator: Marlyn Mayo

Gender: ALL

Age: 18 Years to 75 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06051617

IRB Number: STU-2023-0826

Show full eligibility criteria

Inclusion Criteria:

Individuals must meet the following criteria to be eligible for study participation:
• Must be at least 18 years old.
• Must have a confirmed prior diagnosis of primary biliary cholangitis (PBC)
• Evidence of cirrhosis
• CP Score A or B
• Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
• Individuals must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)

Exclusion Criteria:

Individuals must not meet any of the following criteria to be eligible for study participation:
• Prior exposure to seladelpar
• A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study
• History of liver transplantation or actively listed for cadaveric or planned living donor transplant.
• Decompensated cirrhosis
• Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI
• Hospitalization for liver-related complication within 12 weeks of Screening
• Laboratory parameters at Screening:
• Alkaline phosphatase (ALP) \< 1.5× Upper limit of normal (ULN) or ≥ 10×ULN
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5×ULN
• Total bilirubin (TB) ≤ 0.6 × ULN or ≥ 5 × ULN
• Platelet count ≤50×10\^3/µL
• Albumin ≤2.8 g/dL
• Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m\^2
• MELD score \>12. For individuals on anticoagulation medication, baseline International normalized ratio (INR) determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor.
• Serum alpha-fetoprotein (AFP) \>20 ng/mL
• INR \>1.7
• CP-C cirrhosis
• History or presence of other concomitant liver diseases

Interventions: DRUG: Seladelpar, DRUG: Placebo

Conditions: Primary Biliary Cholangitis

Keywords: Primary Biliary Cholangitis (PBC), PBC

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis (ELFIDENCE)

Description:

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) and cirrhosis (scarring of the liver). PBC is a slowly progressive disease, characterised by damage to the bile ducts in the liver, leading to a build-up of bile acids which causes further damage. The liver damage in PBC may lead to cirrhosis. PBC may also be associated with multiple symptoms. Many patients with PBC may require liver transplant or may die if the disease progresses and a liver transplant is not done. This study will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment) and will last up to 3.5 years for each participant. The main aim of this study is to determine if elafibranor is better than placebo in preventing clinical outcome events showing disease worsening (including progression of disease leading to liver transplant or death). This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itching and tiredness.

Contact(s):

studyfinder@utsouthwestern.edu

Principal Investigator:

Gender: ALL

Age: 18 Years to old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06016842

Show full eligibility criteria

Inclusion Criteria : * Male or female participants must be ≥18 years of age at the time of signing the informed consent. * Participants with a definite or probable diagnosis of primary biliary cholangitis (PBC) * Participants with cirrhosis at SV1. • Participants must be Child Pugh A or Child Pugh B. * Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria : * History or presence of other concomitant liver disease including but not limited to: * i) Primary sclerosing cholangitis (PSC). * ii) Autoimmune hepatitis (AIH) by simplified Diagnostic Criteria of the International Autoimmune Hepatitis Group (IAIHG) ≥6, or if treated for an overlap of PBC with AIH, or if there is clinical suspicion and evidence of overlap AIH features, that cannot be explained alone by insufficient response to UDCA. * iii) Positive hepatitis B surface antigen (HBsAg). Participants with negative HBsAg and positive hepatitis B core antibody (HBcAb) may be eligible if hepatitis B virus deoxyribonucleic acid (HBV DNA) is negative. * iv) Hepatitis C virus (HCV) infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid (RNA) (Note: Participants with positive anti-HCV antibody due to previously treated HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained viral response has been documented). * v) Alcohol-associated liver disease (ALD). * vi) Nonalcoholic steatohepatitis (NASH). * vii) Other chronic liver diseases, such as alpha-1 antitrypsin deficiency. * History or presence of clinically significant hepatic decompensation, including: * i) History of liver transplantation, current placement on a liver transplant list, current model for end-stage liver disease including (MELD) 3.0 score \>12 due to hepatic impairment. * ii) Evidence of complications of cirrhosis, including hepatic decompensation or evidence of significant portal hypertension complications including presence of uncontrolled ascites; history of variceal bleeding or related interventions (e.g. variceal banding, or transjugular intrahepatic portosystemic shunt placement); presence of hepatic encephalopathy Grade 2 or higher per West-Haven criteria; history or presence of spontaneous bacterial peritonitis. Note: participants with low-risk varices (Grade I) without history of bleeding or other treatment may be eligible to enrol. * iii) Hepatorenal syndrome (HRS) (type I or II ). • vi) Hospitalisation for liver-related complication within 12 weeks prior to SV1. * Known history of human immunodeficiency virus (HIV) infection or having a positive confirmatory test for HIV type 1 or 2. * Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease). * Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant conditions that are not well controlled. * Non-hepatic medical conditions that may diminish life expectancy to \<2 years, including known cancers. * History of hepatocellular carcinoma. * Alpha-fetoprotein (AFP) \>20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of hepatocellular carcinoma. * Known malignancy or history of malignancy within the last 5 years. Participants with non-melanoma skin cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below: • i) 3 months prior to baseline: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid or nitrofurantoin). * Participants who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer, prior to the screening period. i) If the previous study was for an experimental therapy being studied for potential benefit in PBC, and the potential therapeutic agent was proven to have no beneficial effect in PBC and there are no safety concerns, the participant may enrol after 30 days or 5 half-lives from the last dose of the therapeutic agent, whichever is longer.ii) For therapeutic agents being studied for potential benefit in PBC for which it is still unclear if there may be a potential benefit, participants may enrol after 6 months from the last dose of the therapeutic agent. * Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) \>450 msec in males or QTcF \>470 msec in females for participants without bundle branch block. For participants with bundle branch block or other intraventricular conduction delay, a longer QTcF \>480 msec would be exclusionary. * Total bilirubin (TB) \>5x ULN * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>5x ULN at SV1 * Creatinine phosphokinase (CPK) \>2x ULN. * Platelet count \<50,000/μL * International normalised ratio (INR) \>1.8 in the absence of anticoagulant therapy. * Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m2 per the Modification of Diet in Renal Disease (MDRD)-6 Study formula at SV1. * Significant renal disease, including nephritic syndrome, chronic kidney disease (CKD) (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury). * For female participants: known current pregnancy, or has a positive serum pregnancy test, or is breastfeeding. * Participants unwilling or unable to be abstinent from alcohol during the study. * History of alcohol abuse, or other substance abuse within 1 year prior to SV1. * Known hypersensitivity to elafibranor or to any of the excipients of the investigational product(s). * Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. * Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study. * Alkaline phosphatase (ALP) ≥10x ULN. * Albumin \<2.8 g/dL due to impaired hepatic function.

Interventions: DRUG: Elafibranor, OTHER: Matched 80 mg placebo

Conditions: Primary Biliary Cholangitis (PBC)

I'm interested

Share via email

See this study on ClinicalTrials.gov

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)

Description:

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyltransferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: ALL

Age: 18 Years to old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06026410

IRB Number: STU-2024-1021

Show full eligibility criteria

Inclusion Criteria:

* At least 18 years of age. * Histologically or cytologically confirmed advanced solid tumors * Arm #1 (KO-2806 monotherapy): Patients who have progressed on, or are refractory to, standard of care (SOC) treatments with advanced solid tumors, specifically: HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC * Arm #2 (Combination): Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment-naïve or have received any prior systemic treatment for locally advanced and metastatic RCC. * Arm #3 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC. * Arm #4 (Combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #5 (Cabozantinib monotherapy): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #6 (Cabozantinib rollover to combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #7 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks. * Acceptable liver, renal, endocrine, and hematologic function. * Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

* Any use of anticancer therapy within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1. * Prior treatment with an FTI or HRAS inhibitor. * Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery. * Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases. * Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent. * Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions). * Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. * Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs. * Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebrovascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure. * Other invasive malignancy within 2 years. * Other protocol-defined exclusion criteria may apply.

Interventions: DRUG: Darlifarnib, DRUG: Cabozantinib, DRUG: Adagrasib

Conditions: Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC), Renal Cell Carcinoma (Kidney Cancer), Non Clear Cell Renal Cell Carcinoma (nccRCC), Colon, Kidney, Lung/Thoracic, Pancreas

Keywords: HRAS, KRAS, NRAS, Farnesyltransferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1, KRAS G12C inhibitor, NSCLC, ccRCC, RCC, PDAC, CRC

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

EGCG for Hepatocellular Carcinoma Chemoprevention (CATCH-B)

Description:

This phase II trial tests epigallocatechin gallate (EGCG) for its efficacy and safety in preventing development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Yujin Hoshida

Gender: ALL

Age: 18 Years to old

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06015022

IRB Number: STU-2023-0233

Show full eligibility criteria

Interventions: DRUG: Epigallocatechin gallate (EGCG), OTHER: Placebo

Conditions: Cirrhosis, Liver, Liver

Keywords: hepatocellular carcinoma, chemoprevention, liver cancer

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

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

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Cecilia Ethun

Gender: ALL

Age: 18 Years and over

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05863195

IRB Number: STU-2024-0075

Show full eligibility criteria

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 previous first-line chemotherapy that meets 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 measurable disease * Patients who have disease progression, in the judgement of the treating multidisciplinary team, are not eligible. * This requirement does not apply to patients who developed new colorectal liver metastases within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer * 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. * NOTE: Patients who are deemed technically resectable but simultaneous biologically unresectable are not eligible. * Patient must undergo multiphase imaging of the chest, abdomen, and pelvis inclusive of CT and/or MRI angiography to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 28 days prior to randomization. * NOTE: If the patient had remote liver-arterial phase imaging greater than 4 weeks from randomization, then only a single phase (portal venous) intravenous contrasted staging CT and/or MRI of the chest/abdomen/pelvis is required. * 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. * 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 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. * Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to protocol randomization) * Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 28 days prior to protocol randomization) * Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol randomization) * Total Bilirubin =\< 1.5 mg/dL (obtained =\< 28 days prior to protocol randomization) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol randomization) * Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 28 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

Interventions: BIOLOGICAL: Bevacizumab, DRUG: Capecitabine, BIOLOGICAL: Cetuximab, PROCEDURE: Computed Tomography, DRUG: Floxuridine, DRUG: Fluorouracil, PROCEDURE: Implantation, PROCEDURE: Intrahepatic Infusion Procedure, DRUG: Irinotecan, DRUG: Leucovorin, PROCEDURE: Magnetic Resonance Imaging, DRUG: Oxaliplatin, BIOLOGICAL: Panitumumab, PROCEDURE: Single Photon Emission Computed Tomography

Conditions: Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma, Colon, Liver, Rectum

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

The GORE VBX FORWARD Clinical Study: A Comparison of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis to Bare Metal Stenting for Patients With Complex Iliac Occlusive Disease

Description:

The objective of this prospective, multicenter, randomized, controlled clinical trial is to demonstrate the superiority of the VBX Device for primary patency when compared to bare metal stenting in complex iliac occlusive disease.

Contact(s):

Call 214-648-5005
studyfinder@utsouthwestern.edu, Antonio.SolanoAvendano@UTSouthwestern.edu

Principal Investigator: Melissa Kirkwood

Gender: ALL

Age: 18 Years and over

Phase: NA

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05811364

IRB Number: STU-2023-0754

Show full eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years at time of informed consent signature * Informed Consent Form (ICF) is signed by the subject * Subject can comply with protocol requirements, including follow-up * Patient has symptomatic claudication, rest pain, or minor tissue loss (Rutherford Category 2-5) * Patient has de novo or restenotic lesion(s) found in the common and/or external iliac artery(ies) * Patient has: Unilateral or bilateral single or multiple lesions (\>50% stenosis or chronic total occlusion) each between 4 and 11 cm in length * Patient has a target vessel diameter visually estimated to be approximately between 5 mm and 13 mm * Patient has a sufficient (\<50% stenotic) common femoral artery and at least one sufficient (\<50% stenotic) femoral artery (deep or superficial). * Patient has at least one sufficient (\<50% stenotic) infrapopliteal run-off vessel.

Exclusion Criteria:

* Life expectancy \<1 year * Patient is pregnant at time of informed consent. * Patient has a known allergy to stent or stent graft components (including nitinol, stainless steel, or heparin). * Patient has severe chronic renal insufficiency (serum creatinine level \> 2.5mg/dL) and not undergoing hemodialysis. * Patient has evidence of a systemic infection. * Patient has a known intolerance to antithrombotic medications that prevent compliance with study or control device Instructions for Use. * Patient has had vascular catheterization of the lower extremities within 30 days of randomization (excluding diagnostic angiograms for the study procedure). * Patient has previous stenting in the iliac arteries. * Patient has previous surgical bypass in the target limb. * Patient is currently participating in another investigative clinical study unless received written approval by the sponsor. * Patient has a lesion requiring drug-coated balloon angioplasty, atherectomy, lithotripsy, or any ablative device to facilitate stent delivery. * Patient has an abdominal aortic artery lesion or aneurysm. * Patient has a lesion that requires stent placement within 2 cm of the inguinal ligament. * Patient has isolated common iliac artery stenosis that can be treated with a single device (i.e., common iliac artery stenosis that does not require kissing stents or extend into the external iliac artery). * Patient has outflow disease that requires concomitant interventions (i.e. common femoral endarterectomy or femoral / tibial revascularization).

Interventions: DEVICE: Stenting of the Common and/or External Iliac Arteries with the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis, DEVICE: Stenting of the Common and/or External Iliac Arteries with Bare Metal Stent

Conditions: Aortoiliac Occlusive Disease, Peripheral Arterial Disease, Other Hematopoietic

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma (EMERGE 101)

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Avanthi Shah

Gender: ALL

Age: 2 Years to 30 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05734066

IRB Number: STU-2023-0156

Show full eligibility criteria

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

Interventions: DRUG: Lurbinectedin

Conditions: Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Ewing Sarcoma, Sarcoma

Keywords: Solid Tumors, lurbinectedin, ewing's sarcoma, soft tissue sarcoma, sarcomas

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)

Description:

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. 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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05614739

IRB Number: STU-2023-0080

Show full eligibility criteria

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: Presence of an alteration in FGFR3 or its ligands * Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration * Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic * Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration * Measurability of disease: * Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1) * Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1 * Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5 * Less than or equal to 2 for Cohorts B1, B2, B4, and C1 * 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, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting * There is no restriction on number of prior therapies * Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC * FGFR inhibitor specific requirements: * Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required * Cohort B1/B4: Participants must have been previously treated with erdafitinib * Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve

Exclusion Criteria:

* Participants with primary central nervous system (CNS) malignancy * Untreated or uncontrolled CNS metastases * Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible * 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

Interventions: DRUG: LOXO-435, DRUG: Pembrolizumab, DRUG: enfortumab vedotin

Conditions: 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

Keywords: Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial

Description:

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Devin Jones

Gender: ALL

Age:

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05564377

IRB Number: STU20251146

Show full eligibility criteria

Inclusion Criteria:

* Patient must have measurable disease * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of \>= 50% or Karnofsky performance status of \>= 50% * Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider * All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL) * Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria: * Patients must have progressed on at least one line of standard systemic therapy OR * Patients whose disease has no standard treatment that has been shown to prolong overall survival * Patient must meet one of the following requirements: * Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR * Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria: * Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial * Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response \[CR\] or partial response \[PR\]) to any intervening therapy after collection of the tissue * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR * Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria: * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available * NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only * NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial

Interventions: DRUG: Alpelisib, DRUG: Binimetinib, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Fluorouracil, DRUG: Fulvestrant, DRUG: Ipatasertib, DRUG: Leucovorin, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Mutation Carrier Screening, DRUG: Neratinib Maleate, DRUG: Nilotinib Hydrochloride Monohydrate, DRUG: Olaparib, DRUG: Oxaliplatin, DRUG: Paclitaxel, DRUG: Palbociclib, BIOLOGICAL: Panitumumab, PROCEDURE: Positron Emission Tomography, DRUG: Selumetinib Sulfate, DRUG: Sotorasib

Conditions: Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: David Hsieh

Gender: All

Age: 18 Years and over

Phase: Phase 1/Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05440708

IRB Number: STU-2022-0622

Show full eligibility criteria

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.

Interventions: Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab

Conditions: Hepatocellular Carcinoma, Liver

Keywords: Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

Description:

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. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) 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).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Nisha Unni

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05216432

IRB Number: STU-2023-1126

Show full eligibility criteria

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 \[Escalation\] - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 \[Expansion\] - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively. Key Inclusion for RLY-2608 Single Agent Arm * \[For Part 1: Escalation\]: Evaluable disease per RECIST v1.1 * \[For Part 2: Expansion\]: 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 In addition, the SRC (with Sponsor approval) may choose to open additional group(s) of 20 participants to study the clinical activity, safety, and PK/PD with other specified solid tumor types. Key Inclusion for Combination Arms: * Doublet combination arms \[Part 1 and Part 2\]: Evaluable disease per RECIST v1.1 * Triplet combination arms: * \[Part 1 and Part 2 Dose Expansion, Group 1\]: Evaluable disease per RECIST. * \[Part 2 Dose Expansion, Group 2\]: Measurable disease per RECIST. Bone-only lytic or lytic/blastic disease with at least 1 measurable soft-tissue component per RECIST may be eligible. * \[For Part 1 and Part 2\]: 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- locally advanced or metastatic breast cancer that is not amenable to curative therapy and must have initiated treatment with a gonadotropin-releasing hormone (GnRH) agonist at least 4 weeks prior to start of study drug with continuation of GnRH agonist for the duration of study treatment (GnRH agonist recommended for males). * Had previous treatment for breast cancer with: \[Does not apply to triplet combination arms, Part 2 Dose Expansion, Group 2\]:
• ≤1 line of chemotherapy in the metastatic setting
• ≥1 CDK4/6 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 \[For double combination arm; Part 2 Dose Expansion, Group 2\]: Received prior treatment with a PI3Kα, AKT, or mTOR 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. \[For triple combination arms; Part 1 dose escalation\]: Participants who had previous treatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due to participant/physician decision, intolerance, or disease progression will be considered. \[For triple combination arms, Part 2 Dose Expansion, Group 2\]: Participants must be intolerant to or have declined standard therapy for locally advanced or metastatic HR+/HER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4/6inhibitors are allowed as follows:
• Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen.
• If a CDK4/6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred/progressed \>12 months after completion of the CDK4/6 inhibitor portion of (neo)adjuvant therapy Key Exclusion Criteria Prior treatment with:
• PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).
• Immune checkpoint inhibitors.
• Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only: i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locally advanced or metastatic disease. iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months. Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate for the combination. Past medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms. The following cardiac criteria: * Mean resting corrected QT interval (QTc) \>460 msec * For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol. CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms

Interventions: DRUG: RLY-2608, DRUG: Fulvestrant, DRUG: Palbociclib 125mg, DRUG: Ribociclib 400mg, DRUG: Ribociclib 600mg, DRUG: PF-07220060 100mg, DRUG: PF-07220060 300 mg

Conditions: PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Breast - Female, Breast - Male

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk (TORCH)

Description:

Prospective randomized, multi-center, double blind placebo-controlled trial to assess the chemopreventive impact of atorvastatin (20 mg oral) vs placebo in up to 60 adults with advanced fibrosis at high risk of developing HCC.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Yujin Hoshida

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05028829

IRB Number: STU-2022-0471

Show full eligibility criteria

Inclusion Criteria:

• Willing and able to provide informed consent
• Male or female age \> 18 years at time of consent
• Clinically or histologically diagnosed advanced liver fibrosis or cirrhosis, as defined by one or more of the following: * Liver biopsy demonstrating advanced fibrosis or cirrhosis (METAVIR 3-4) * Fibroscan or MR elastography consistent with advanced fibrosis or cirrhosis * Imaging showing cirrhotic-appearing liver with signs of portal hypertension * Advanced fibrosis or cirrhosis documented clinically by a treating physician
• High-risk for HCC at screening according to the FIB-4 index
• PLSec score ≥ 3 measured in screening blood samples from the FIB-4-high individuals.
• Liver imaging within 6 months of Day 1 is required in cirrhotic subjects only, to exclude HCC
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Willing and able to undergo protocol blood sampling
• Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments

Exclusion Criteria:

• Diagnosis of any of the following forms of chronic liver disease: * alpha-1-antitrypsin (A1AT) deficiency, Wilson disease, hemochromatosis, iron overload, prior known or suspected drug-induced liver injury (DILI) * Patients with PBC, PSC, AIH, or stable hemochromatosis may be included if their liver disease etiology overlaps with that of steatotic liver disease (SLD)
• Current or prior history of any of the following: \- Clinically significant illness or any other major medical disorder that in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol
• Known positivity for HIV infection
• Active, untreated HCV infection \- Patients with prior history of HCV who achieved sustained virologic response (SVR) \>12 from Day 1 may be included in the study
• Uncontrolled chronic HBV \- Patients with well controlled disease with \>12 months of stable medication use (or no medication use, in those persons for whom anti-HBV therapy is not indicated)
• Clinical hepatic decompensation, defined as Child's Pugh class \>B7 or C cirrhosis \- Patients with Child's Pugh score of 7, class B, may be included in the study
• History of biliary diversion
• Solid organ transplant
• Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
• Pregnant or Nursing Females (a negative serum pregnancy test is required at screening for WOCBP)
• Life threatening SAE during the screening period
• Subjects having the following laboratory parameters at screening * ALT \> 10 x ULN * AST \> 10 x ULN * Hemoglobin \< 8.5 g/dl * Serum creatinine \> 2.0 mg/dL * CK \> 3x ULN
• Females who may wish to become pregnant and/or plan to undergo egg harvesting during the study and up to 30 days of the last dose of study drug
• WOCBP must abstain from breastfeeding and be willing to use effective birth control during through the week 4 post treatment follow-up visit
• Clinically relevant alcohol or drug abuse within 12 months of screening
• Use of any prohibited concomitant medications as described in Section 9.1.1
• Use of a statin medication within 90 days of Day 1 visit \- Subjects who are on a current statin at time of consent must be willing to undergo a 90-day washout period prior to randomization
• Known hypersensitivity to atorvastatin
• Current or planned participation in an investigational new drug (IND) trial from 30-days prior to randomization through the week 4 post treatment follow-up visit

Interventions: DRUG: Atorvastatin 20mg, DRUG: Placebo

Conditions: Liver Fibroses, Cirrhosis

Keywords: Liver Disease, Chemoprevention, HCC, Atorvastatin

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Search Results

A Study to Assess How Well and Safely Elafibranor Works in Adult Participants With Primary Sclerosing Cholangitis (ELASCOPE)

A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (Beacon-BTC)

Evaluation of Liver Stiffness Performance, by FibroScan®, to Detect Elevated Central Venous Pressure (CVP)

A Study to Assess Adverse Events and Change in Disease Activity in Participants 12 Years of Age or Older With Locally Advanced or Metastatic Solid Tumors That Harbor MET Amplification Receiving Intravenously Infused Telisotuzumab Adizutecan

Personalized Radiotherapy for Individualized Treatment Strategies and Monitoring (PRISM) (PRISM)

A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors

ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)

Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Breast Cancer w/Liver Dominant Disease (DELUMA)

Ligufalimab and Cadonilimab in Advanced Liver Cancers

Lead-212 PSV359 Therapy for Patients With Solid Tumors

Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010)

Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

CEUS vs. AMRI for HCC Detection in Patients With Indeterminate Liver Nodules

Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

National Liver Cancer Screening Trial (TRACER)

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (COLT)

Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)

A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis (ELFIDENCE)

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)

EGCG for Hepatocellular Carcinoma Chemoprevention (CATCH-B)

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

The GORE VBX FORWARD Clinical Study: A Comparison of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis to Bare Metal Stenting for Patients With Complex Iliac Occlusive Disease

Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma (EMERGE 101)

FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)

Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial

A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma

First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk (TORCH)

Email this study information to me

Contact the study team