Search Results Within Category "Digestive Systems & Liver Disease"
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
National Liver Cancer Screening Trial (TRACER)
The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• 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
• 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
IDEAL: Intended to Determine the Effects of Seladelpar on Normalization of Alkaline Phosphatase Levels in Subjects With Primary Biliary Cholangitis (PBC) and an Incomplete Response or Intolerance to Ursodeoxycholic Acid (UDCA) (IDEAL)
studyfinder@utsouthwestern.edu
• 18 to 75 years old (inclusive)
• Male or female with a diagnosis of PBC based on history
• UDCA for the 12 months prior to screening (with stable dose for \>3 months prior to screening) OR intolerant to UDCA (last dose of UDCA \>3 months prior to screening)
• ALP \>1×ULN and \<1.67×ULN
• 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 subjects 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.
• Previous exposure to seladelpar (MBX-8025)
• A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study (eg, cancer) or confound its results
• Advanced PBC as defined by the Rotterdam criteria
• Laboratory parameters measured by the Central Laboratory at screening
• Clinically important hepatic decompensation
• Other chronic liver diseases
• Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
• Clinically important alcohol consumption, defined as more than 2 drink units per day in women and 3 drink units per day in men, or inability to quantify alcohol intake reliably
• History of malignancy diagnosed or treated, active or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening
• History of drug abuse
• Treatment with obeticholic acid or fibrates 6 weeks prior to screening
• Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids within 2 months prior to screening
• Initiation or dose adjustment of anti-pruritic drugs within 1 month prior to screening
• Immunosuppressant therapies within 6 months prior to screening
• Other medications that affect liver or GI functions, as well as the roux-en-y gastric bypass procedure, may be prohibited and should be discussed with the medical monitor on a case-by-case basis
• Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
• Pregnancy or plans to become pregnant, or breastfeeding
• Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)
To Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, lakeisha.johnson@utsouthwestern.edu
• Must be 18 to 75 years old (inclusive)
• Must have a confirmed prior diagnosis of 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 subjects 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
• Subjects must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)
• 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:
• ALP ≥10×ULN
• ALT or AST ≥5×ULN
• TB ≥5×ULN
• Platelet count ≤75×10\^3/µL
• Albumin ≤2.8 g/dL
• Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m\^2
• MELD score \>12. For subjects on anticoagulation medication, baseline 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
Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Colorectal Cancer
The main purpose of this clinical trial is to learn about the good and the bad effects of all trans retinoic acid (ATRA), atezolizumab and bevacizumab as a possible treatment for advanced colorectal patients. Participants will be treated with the following combination of these drugs: 1. ATRA will be given in a pill form to be taken twice a day at home for 7 days starting on day 1 of a cycle. 2. Atezolizumab will be given through a vein in arm or through mediport over 60-90 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW. 3. Bevacizumab will be given through a vein in arm or through mediport over 20-40 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Histologically proven stage IV colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1- 2, M1). Tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve).
• Known DNA mismatch repair or microsatellite instability status. Only one of these tests is required for enrollment as there is 95% concordance rate of these tests.
• The eligible patient's tumors be classified as proficient in DNA mismatch repair (pMMR) by immunohistochemistry (IHC) for MMR protein expression (MLH1, MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), PMS2. Tumors with intact expression of all MMR proteins will be considered pMMR.
• OR
• The eligible patient's tumor be classified by Pathologic Complete Response (pCR) as stable microsatellite stability status (MSS) for panel of microsatellite markers, OR
• MSS by commercially available next generation sequencing testing. OR
• If tumor-based test are not feasible, then commercially available circulating tumor DNA tests showing MSS status will also be acceptable.
• The patients should have received at least two lines of systemic chemotherapies in metastatic setting. They should have received fluoropyrimidine, irinotecan, and oxaliplatin unless medically contraindicated. Prior anti-VEGF (vascular endothelial growth factor) therapy is accepted for enrollment since anti-VEGF therapy maintains its benefit across several lines of therapy. If clinically appropriate, the patients should have received anti-EGFR (epidermal growth factor receptor) therapy for all Rat sarcoma (RAS) wild type colorectal cancers and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation-directed therapy for BRAF V600E mutant colorectal cancers.
• Age 18 and above
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
• Adequate organ and marrow function
• Hemoglobin ≥ 9.0 g/dL
• Lymphocyte count > 0.5 x 109/L (500/uL)
• Absolute Neutrophil Count (ANC) ≥ 1500 mm3
• Platelet Count ≥ 100,000 mm3
• Creatinine ≤ 1.5 x upper limit of normal or Calculated Creatinine Clearance ≥ 45 mL/min
• Total Bilirubin ≤ 1.5 x upper limit of normal unless Gilbert syndrome with the following exception: Patients with known Gilbert disease: serum bilirubin >3 ULN
• Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤ 2.5 x upper limit of normal
• The subject's urinary protein is < 1+ on dipstick or routine urinalysis; if urine protein > 2+, a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV testing at screening, with following exception: patients with positive HIV tests at screening are eligible provided they are stable on anti-retroviral therapy, have a cluster of differentiation 4 (CD4) count > 200/uL, and have undetectable viral load.
• Negative hepatitis B surface antigen (HBsAg) test at screening.
• Ability to understand and the willingness to sign a written informed consent
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control with <1% failure rate, tubal ligation, male sterilization; abstinence) prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. Women must refrain from donating eggs during this same period. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months). • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
• Microsatellite unstable colorectal (MSI-H) cancers identified by PCR testing OR by commercially available Next-generation sequencing (NGS) and Circulating tumor DNA (ctDNA) testing OR by loss of expression of one or more of the MMR enzymes (MLH1, MSH2, MSH6, PMS2) on immunohistochemistry. Only one such test is required to confirm eligibility.
• Current active known or suspected autoimmune disease such as including colitis, inflammatory bowel disease (i.e. ulcerative colitis or Crohn's disease), rheumatoid arthritis, pan-hypopituitarism, History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan (), adrenal insufficiency treated with immunosuppressive steroids and biologics treatment. Patients with controlled disease with no active treatment or prednisone < 10 mg daily may be eligible based on treating physician assessment. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, history of radiation pneumonitis in the radiation field (fibrosis) is permitted or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
• Prior use of atezolizumab or ATRA is not eligible. Prior use of any other immunotherapy such anti programmed death-ligand 1 (PD-L1), anti- programmed cell death protein 1 (PD-1), Anti-CTLA4 will also be excluded.
• Chemotherapy, radiotherapy, or other cancer therapy within 3 weeks prior to starting study treatment.
• Subjects must have recovered from prior treatment-related to toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study within 28 days prior to initiation of study treatment
• Untreated brain metastases are not allowed. If prior treatment of brain metastases with surgery and/or radiation therapy has been provided, those patients will be clinically stable and not requiring escalating doses of steroids.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ATRA, atezolizumab, and bevacizumab or other agents used in study.
• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), history of hypertensive crisis or hypertensive encephalopathy. Clinically significant cardiovascular disease, such as cerebrovascular accident within six months prior to enrollment, myocardial infarction within six months of prior to enrollment, unstable angina History of hypertensive crisis or hypertensive encephalopathy. If patient has previously received bevacizumab safely after that episode, with adequate BP control, then patients will be eligible.
• Uncontrolled inter current illness including, but not limited to, ongoing or severe infection within 4 weeks prior to initiation of study treatment that could impact patient safety, symptomatic congestive heart failure with reduced ejection fraction history and the New York Heart Association (NYHA) Functional Classification class III or IV, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months for atezolizumab and 6 month for bevacizumab after the final dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment
• History of leptomeningeal disease or un-controlled tumor related pain. Patient requiring pain medications should be on a stable regimen. Symptomatic lesions (e.g. bone metastasis or metastasis causing nerve impingement) amenable to radiation therapy should be treated before enrollment and patient should have recovered from that radiation. No required minimum recovery period from the radiation.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• History of Grade 4 venous thromboembolism. If previously have received bevacizumab safely after that episode then patients will be eligible
• History of Grade > 2 hemoptysis (defined as > 2.5 mL of bright red blood per episode) within 1 month prior to screening
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
• Currently active abdominal fistula, GI perforation, intra-abdominal abscess, or active GI bleeding requiring transfusion of blood products or hospitalization within 6 months
• Serious, non-healing wound, active non-healing ulcer, or untreated bone fracture
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Current or recent (10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day), or clopidogrel (>75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. Direct oral anticoagulant use such as Rivaroxaban (Xarelto) and Apixaban (Eliquis) is allowed
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL or corrected serum calcium >ULN)
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Known active hepatitis B or C, active tuberculosis and known uncontrolled HIV
Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)
The goal of the Lead-in phase of the study is to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy. The goal of the Expansion phase of the study is to evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Must have locally advanced or metastatic ccRCC and have progressed or relapsed after at least 1 prior anti-VEGF/VEGFR systemic therapy and 1 ICI.
• Measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• KPS score of at least 70%
• Able to swallow oral medications.
• Active CNS metastases and/or carcinomatous meningitis
• Has had any major cardiovascular event within 6 months or clinically significant cardiovascular disease
• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before administration of study drug.
• Has known HIV
• History of hepatitis B or known active hepatitis C infection
• Has received prior treatment with NKT2152, other HIF2α inhibitors, other CDK 4/6 inhibitors, palbociclib, or sasanlimab
• Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before administration of the first dose of study treatment
• Corrected QT interval calculated by Fridericia formula (QTcF) > 480 ms within 28 days prior to first dose
• Hypoxia or requires intermittent or chronic supplemental oxygen or any chronic lung condition which has required supplemental oxygen in the past
• Has a history of interstitial lung disease
• Has any active or recent history of a known or suspected autoimmune disease
A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors
The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.
• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (SKYSCRAPER-14)
The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC).
studyfinder@utsouthwestern.edu
Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study
This phase III trial compares the effect of stero-ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with kidney cancer that has spread from where it first started (primary site) to a limited (2-5) number of places in the body (metastatic). Study doctors want to find out if this approach is better or worse than the usual approach for metastatic kidney cancer. The usual approach is defined as the care most people get for metastatic kidney cancer which includes systemic therapy such as immunotherapy (given through the veins) and/or small molecular inhibitor (tablets taken by mouth). Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR uses special equipment to position a patient and deliver radiation to tumors with high precision. Giving SAbR prior to systemic therapy may kill more tumor cells than the usual approach, which is systemic therapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Patient must be >= 18 years of age
• Patient must have a pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma (RCC) prior to randomization
• Patient may have any RCC histology except a histology that has a sarcomatoid component
• Patient must have primary site addressed by local therapy. If the primary RCC is intact, the patient must undergo local treatment to the primary before randomization
• Patient must have favorable or intermediate International Metastatic RCC Database Consortium (IMDC) risk (0-2) at the time of randomization
• Patient must have a total of between 2 and 5 metastatic lesions, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with imaging obtained within 45 days prior to randomization
• Patient must have a documentation from a radiation oncologist confirming that all sites are amenable to SAbR
• Patient may have received prior therapy in the adjuvant setting as long as potential trial participants have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
• 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
• 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
• All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
• A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point
• Has not undergone a hysterectomy or bilateral oophorectomy
• 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 have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have a Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Patients must have adequate organ and bone marrow function as per the recommended guidelines and the respective Food and Drug Administration [FDA] package insert required for the systemic therapy chosen by the treating oncologist. We recognize that patients may have varying levels of renal and liver function that will impact which systemic therapy is appropriate for the patient. We do not require all patients to have specific baseline laboratory thresholds but do ask the treating oncologist to attest that the patient has adequate organ and bone marrow function to safely receive one of the first line systemic therapies listed in the protocol as a standard of care treatment option
• 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
• For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study
• In order to participate in the QOL portion of the protocol, the patient must speak one of the languages in which the NFKSI-19 and EQ-5D-5L is available
• NOTE: Sites cannot translate the associated QOL forms
• Patient must not have brain metastases
• Patient must not have metastasis involving the following locations: ultra-central (within 2cm of carina) lung, invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum), skin, and scalp
• Patient must not have received any prior systemic therapy (except for adjuvant setting) for metastatic RCC
• Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
• Active tuberculosis (purified protein derivative [PPD] response without active TB is allowed)
• Uncontrolled hypertension (systolic blood pressure [BP] > 190mmHg or diastolic BP > 110mmHg)
• Major surgery within 30 days prior to randomization
• Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization
• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], cerebrovascular accident [CVA], etc.) events within 180 days prior to randomization
• Moderate or severe hepatic impairment (child-Pugh B or C)
• Untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed. Treated PE or DVT is allowed > 30 days from diagnosis and when not resulting in respiratory impairment
• Unstable cardiac arrhythmia within 180 days prior to randomization
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization
• History of or active inflammatory bowel disease
• Malabsorption syndrome within 30 days prior to randomization
• 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
• 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 and for 6 months after the last dose of protocol treatment
A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma
This study will be conducted in 2 parts. The first part is a phase 1 single-agent dose escalation,optimization, and expansion study of tegavivint in patients with advanced HCC after failure of at least one line of prior systemic therapy. In the second part of the study, the combination of tegavivint plus pembrolizumab will be assessed with a limited dose escalation followed by a randomized dose optimization.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Male or female, 18 years of age or older
• Confirmed diagnosis of HCC by either: Histologically or cytologically documented HCC based on pathology report or Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria
• Presence of AXIN1 or CTNNB1 mutation is required for all patients, except those enrolled in the single agent dose escalation Documentation of comprehensive genomic profiling to assess for mutations in β-catenin signaling including AXIN1 and CTNNB1 is required for all patients
• Ascertainment from fresh biopsy or liquid biopsy during screening is allowed.
• Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
• Child-Pugh class A or ≤ 7 class B liver score (no hepatic encephalopathy) within 7 days of first dose of the investigational product(s)
• Disease progression, intolerance or contraindication to at least one line of systemic therapy for advanced HCC Prior treatment with a PD-1/PD-L1 inhibitor for at least one administration
• Measurable disease as defined by RECIST 1.1
• Willingness and ability to provide tumor biopsies during screening and while on treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of the investigational product(s)
• Patients must have organ and marrow function as defined below within 7 days of the first dose of the investigational product(s):
• Absolute neutrophil count (ANC) ≥ 1.2 x 109/L
• Platelets ≥ 60 x 109/L; no transfusion within 7 days prior to assessment
• Hemoglobin ≥ 9 g/dL (red blood cell transfusion or growth factors support is not allowed in the 14 days prior to the screening laboratory assessment)
• Total bilirubin ≤ 2 mg/dL, or direct bilirubin ≤ upper limit of normal (ULN) for those with total bilirubin >2 mg/dL
• AST and ALT ≤ 5 x ULN
• Estimated creatinine clearance (CrCl) by the Cockcroft-Gault equation or measured ≥ 60 mL/min.
• Albumin ≥ 3.0 g/dL
• International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• Washout period prior to Day 1 of Cycle 1:
• At least 21 days from the last dose of prior systemic anticancer treatment
• At least 14 days from palliative radiotherapy (≤ 10 fractions or ≤30 gray [Gy] total dose or at least 28 days from radiotherapy > 30 Gy)
• Grade ≤ 1 toxicity due to any previous cancer therapy according to the NCI-CTCAE, v.5.
• Grade 2 is allowed in case of alopecia and/or peripheral sensory neuropathy.
• Participants with past HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention and HCV viral load must be below the limit of quantification.
• Participants with controlled HBV will be eligible if they meet the following criteria:
• Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of study drug. Patients on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention.
• Patients who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis.
• Patients must have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Patients receiving therapy with other anti-neoplastic or experimental agents
• Patients receiving concomitant strong inhibitors of CYP3A4/5 that cannot be discontinued 7 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
• Patients receiving concomitant inducers of CYP3A4/5 that cannot be discontinued at least 14 days prior to Cycle 1 Day 1.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint, or other agents used in study
• Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy.
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
• Known central nervous system (CNS) involvement
• Uncontrolled concurrent illness including, but not limited to:
• Ongoing or active infection (exception: HBV infection - see inclusion criteria)
• Unhealed wounds or presence of any external drainage
• Psychiatric illness/social situations that would limit compliance with study requirements; discuss with Medical Monitor if there are any questions
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• Congestive heart failure, NYHA > Class II
• Left ventricular ejection fraction < 50%
• Unstable angina pectoris or cardiac arrhythmia
• Baseline QTc (Fridericia) ≥ 450 milliseconds. In the event a QTc (Fridericia) measurement is not possible due to factors such as a pacemaker or bundle branch block, the patient may be evaluated by a cardiologist who must document no apparent increased risk for Torsades de Point or other morbidity associated with prolonged QTc. With such documentation, the patient may be eligible based with additional Medical Monitor review.
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
• Myocardial infarct within 6 months before Cycle 1 Day 1
• Clinically significant pericardial disease
• Any major surgery within 21 days prior to Cycle 1 Day 1. Major surgery is defined as any significantly invasive procedure into a major body cavity (abdomen, cranium etc.) and/or surgery requiring extensive recuperation (joint replacement). Please discuss with the Medical Monitor if there are any questions.
• Pregnant and breastfeeding women are excluded from this study. The effects of tegavivint on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tegavivint
• Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one highly effective method of contraception, including hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstaining from sex for the duration of study participation and for at least 4 months following completion of tegavivint and pembrolizumab (if applicable) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with tegavivint.
• Exclusions for patients treated on study with pembrolizumab:
• Have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or have current pneumonitis/interstitial lung disease.
• Prior allogeneic organ or bone marrow transplant
Safety and Clinical Activity of KT-253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors
This Phase 1 study will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and clinical activity of KT-253 in adult patients with relapsed or refractory (R/R) high grade myeloid malignancies, acute lymphocytic leukemia (ALL), R/R lymphoma, and R/R solid tumors. The study will identify the pharmacologically optimal dose(s) of KT-253 as the recommended Phase 2 dose (RP2D), based on all safety, PK, PD, and efficacy data.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• All Participants:
• Eastern Cooperative Oncology Group performance status: 0-2.
• Resolved acute effects of any prior therapy except for alopecia to baseline severity or Grade ≤1 NCI CTCAE and Grade ≤2 neuropathy
• Adequate organ function at screening
• Solid Tumors and Lymphoma (Arm A) ONLY
• Histologically or pathologically confirmed solid tumor or lymphoma.
• Relapsed and/or refractory (R/R) disease to at least two prior standard-of-care treatments or tumors for whom standard therapies are not available.
• Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY
• Primary diagnosis of AML, ALL, High/Very High-risk MDS, MDS/MPN. Must be relapsed/refractory to standard therapies.
• All Participants:
• Ongoing unstable cardiovascular function.
• Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug.
• History of or active concurrent malignancy unless disease-free for ≥ 2 years.
• Exposures to anticancer therapy within 2 weeks or 5 half-lives whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of study drug.
• Known presence of p53 mutation in tumor tissue
• Solid Tumors and Lymphoma (Arm A) ONLY
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
• Autologous or allogenic hematopoietic stem cell transplant (HSCT) within six months prior to first dose of study drug or participant has progressed within six months from the day of stem cell infusion (for lymphoma participants only).
• Advanced high grade myeloid malignancies, and ALL (Arm B) ONLY
• Active CNS leukemia. Participants with symptoms suggestive of CNS disease will require a lumbar puncture to rule out CNS disease.
• Prior chemotherapy/radiation (including craniospinal radiation) within 2 weeks prior to the first dose of study drug.
• Received allogeneic hematopoietic cell transplantation (HCT) <12 weeks prior to first dose or donor lymphocyte infusion (DLI) without conditioning <4 weeks prior to first dose.
• Received autologous stem cell transplant (ASCT) < 4 weeks prior to first dose or the patient has not recovered from transplant associated toxicities to ≤ grade 1 prior to the first dose of study drug.
• Received chimeric antigen receptor therapy or other modified T cell therapy <3 weeks prior to the first dose.
• Patients with signs or symptoms of Grade ≥ 2 acute or chronic graft versus host disease (GVHD) within 2 weeks of enrollment.
Study of JANX008 in Subjects With Advanced or Metastatic Solid Tumor Malignancies
This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Domvanalimab and Zimberelimab in Advanced Liver Cancers
The goal of this clinical trial is to learn about advanced liver and bile duct cancers. The main question it aims to answer is: If the combination of Domvanalimab and Zimberelimab are effective in treating advanced hepatobiliary cancers that have failed prior treatment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Patient must have a histologically confirmed diagnosis consistent with HCC or bile duct cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers); known fibrolamellar HCC, or combined HCC-cholangiocarcinoma will be excluded.
• Locally advanced or metastatic disease
• 2a. Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• 2b. Measurable disease, as defined as lesions that can accurately be measured in at east one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Refractory to or relapsed after prior anti-PD-1/L1 antibody therapy. May have received anti-PD-1/L1 monotherapy or combination therapy as any line of therapy including in the neoadjuvant or adjuvant setting. Patients who discontinued prior immune checkpoint inhibitor treatment due to toxicity are not eligible.
• Availability of recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides in which the biopsy or resection was performed within 3 years. Baseline tissue can be obtained after consent but must be prior to initiation of zimberelimab and domvanalimab. It is strongly recommended that tissue is obtained from biopsies confirming progression of disease on prior therapy so that the patient has not received any intervening systemic anti-cancer treatment from the time that the baseline tissue was obtained.
• Prior locoregional is allowed provided the following are met: 1) at least 2 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation; 2) target lesion has increased in size ≥25% or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A or B7-8 (only for Cohort A)
• ECOG Performance score of 0-1
• Adequate organ and marrow function (without chronic, ongoing growth factor support or transfusion in the last 2 weeks) as defined below:
• 9a. Platelet count ≥ 50,000/mm^3
• 9b. Hgb ≥ 8.5 g/dl
• 9c. Absolute neutrophil ≥ 1,000 cells/mm^3
• 9d. Total bilirubin ≤ 3.0 mg/ml (This will not apply to subjects with Gilbert's syndrome who have persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis, and such patients may be enrolled based in consultation with the principal investigator).
• 9e. INR ≤ 2
• 9f. AST, ALT ≤5 times ULN
• 9g. Calculated creatinine clearance (CrCl) ≥ 40 mL/min. CrCl can be calculated using the Cockroft-Gault method.
• 9h. Albumin ≥ 2.0 g/dl
• All men, as well as women of child-bearing potential, defined as not surgically sterilized and between menarche and 1-year post menopause, must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 4 weeks prior to study entry, for the duration of study participation, and for 120 days after the last dose of zimberelimab or domvanalimab. See contraception guidelines in Appendix 1. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Women of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
• 1. HBV-HCC: Hepatitis B subjects will be allowed if they meet the following criteria: On antiviral therapy for HBV or HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment. Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.
• 2. HCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug. Successful HCV treatment definition: SVR12.
• Ability to understand and the willingness to sign a written informed consent.
• Willing and able to comply with the requirements and restrictions in this protocol.
• Patients who have received the vector, protein subunit, or nucleic acid COVID-19 vaccines are eligible to enroll.
• Prior liver transplant.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug administration.
• History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to:
• 5a. Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying),
• 5b. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs,
• 5c. Clinically significant cardiovascular disease,
• 5d. A condition that may obscure the interpretation of toxicity determination or AEs,
• 5e. History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
• 8a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• 8b. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
• Known history of active bacillus tuberculosis.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses ≤10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease.
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer.
• Prisoners or subjects who are involuntarily incarcerated.
• If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if:
• Has evidence of progression by neurologic symptoms
• Has metastatic brain lesions that require immediate intervention.
• Has carcinomatous meningitis, regardless of clinical stability
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drugs.
• Known hypersensitivity to recombinant proteins, or any excipient contained in the study drug formulations.
Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer
This phase II/III trial compares treatment with encorafenib and cetuximab to usual care (patient observation) for reducing the chance of cancer recurrence after standard surgery and chemotherapy in patients with BRAF-mutated stage IIB-III colon cancer. Encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Giving encorafenib and cetuximab after standard surgery and chemotherapy may be more effective at reducing the chance of cancer recurrence compared to the usual patient observation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• PRE-REGISTRATION (STEP 0) ELIGIBILITY CRITERIA:
• BRAF V600 mutational status may be determined either locally or by central testing. This testing is mandatory prior to registration to determine eligibility. Tissue submission should be initiated as soon after surgery as possible. For tumors evaluated at local laboratories, formalin-fixed paraffin-embedded (FFPE) tumor tissue must still be submitted for central confirmation of BRAF status
• REGISTRATION (STEP 1) ELIGIBILITY CRITERIA:
• Histologically-proven stage III (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C) or high-risk (pT4) stage II colon adenocarcinoma. Tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve) and must have been completely resected
• BRAF V600E mutation
• MMR proficient (pMMR) or microsatellite stable (MSS) tumor
• Histologic documentation: adenocarcinoma
• Stage: III (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C) or high-risk II (pT4)
• Tumor site: colon
• Patients must have received at least 3 months of adjuvant chemotherapy with either leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) (minimum of 5 cycles) or capecitabine and oxaliplatin (CAPOX) (minimum of 3 cycles)
• Adjuvant therapy must be completed at most 8 weeks prior to registration
• No other prior medical therapy (chemotherapy, immunotherapy, biologic, or targeted therapy) or radiation therapy for the current colon cancer is permitted
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelet count >= 75 x 10^9/L
• Hemoglobin > 9.0 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN
• Corrected QT (QTc) Interval =< 480 msec
• Creatinine = calculated (calc.) creatinine clearance >= 40 mL/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• No medical condition such as uncontrolled infection, uncontrolled diabetes mellitus, or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients with known history or current symptoms of cardiac disease or history of treatment with cardiotoxic agents in the last 12 months, 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 uncontrolled or poorly-controlled hypertension (> 180 mmHg systolic or > 130 mmHg diastolic)
• No history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab
• No "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years
• Patients are not considered to have a "currently active" malignancy if they had a gastric or bowel carcinoid < 1 cm, ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS) of the breast without invasive cancer, or endometrial dysplasia/carcinoma in situ
• Patients are not considered to have a "currently active" malignancy if they had a sebaceous neoplasm (sebaceous adenoma, sebaceous epithelioma, sebaceous adenocarcinoma, keratoacanthoma, and squamous cell carcinoma) that was noninvasive
• No known medical condition causing an inability to swallow oral formulations of agents
• No residual Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade >= 2 toxicity from prior chemotherapy, with the exception of grade 2 alopecia or neuropathy
• Drugs that prolong the QTc interval should be avoided if possible, as encorafenib can prolong the QTc interval. Drugs that are generally accepted to have a risk of causing Torsades de Pointes should be discontinued or replaced with drugs that do not carry this risk if at all possible. Patients who receive potential QTc-prolonging medications should be monitored closely
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed during treatment on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed during treatment on this study. Patients must discontinue the drug 14 days prior to registration on the study
Evaluating Safety and Biomarkers Using DK210 (EGFR) for Locally Advanced or Metastatic EGFR+ Tumors
This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• ECOG performance status of 0-1
• Life expectancy of >3 months according to the investigator's judgment
• Solid tumors known for response on Il-2 or Il-10 and/or high expression of EGFR like all Non-small cell Lung, Skin, Head and Neck, Colon, Kidney, Bladder, Pancreatic cancers and all squamous cell carcinoma of other organs can be included with a classical histology report, specific EGFR expression or amplification reports are needed for other solid tumor types like gynecologic, prostate or triple negative breast cancer
• Measurable disease, defined as at least one (non-irradiated) lesion measurable on CT/MRI or bone scan as defined by RECIST 1.1.
• Progressive disease (PD) at study entry defined as one or more of the following criteria:
• Clinical PD with performance decline, clinical symptoms and/or observed tumor growth
• PD documented with imaging showing at least 20% growth (largest diameter) and/or new lesions
• Adequate cardiovascular, hematological, liver, and renal function.
• Subjects have failed one or more lines of systemic therapy and have not been operated on or receiving anti-cancer medication for at least 4 weeks.
• Males and females of childbearing potential must agree to use effective contraception starting prior to the first day of treatment and continuing during treatment
• Additional criteria may apply
• Subjects with documented diffuse peritoneal disease or persistent abundant ascites
• Subjects with known prolonged QtC interval
• Concomitant or recent (<4 weeks or 5 half-lives of the last treatment, whichever is shorter) treatment with agents with anti-tumor activity, including immunotherapies, or experimental therapies. Bone treatments and supportive care can be continued
• Major surgery within 4 weeks, Radiation therapy for the treatment of metastases within less than 3 weeks (if single fraction of radiotherapy, then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening
• Uncontrolled intercurrent illness including, but not limited to, ongoing and uncontrolled infection (TBC, COVID or HIV patients treated with at least two anti-retroviral drugs and control of their infection with at least 500 /mm3 CD4+ T-cells in their blood and patients cured from Hepatitis B or C (i.e negativity of PCR) and liver function compatible with eligibility criteria are allowed to participate), multiple myeloma, multiple sclerosis, myasthenia gravis, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement
• Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study
• Additional criteria may apply
A Study of LSTA1 When Added to Standard of Care Versus Standard of Care Alone in Patients With Advanced Solid Tumors (BOLSTER)
The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in patients with previously untreated cholangiocarcinoma or those that have progressed after first-line treatment for cholangiocarcinoma. The main questions it aims to answer are: - is the new drug plus standard treatment safe and tolerable - is the new drug plus standard treatment more effective than standard treatment
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Long-term Extension Study of Ligelizumab in Food Allergy
This is an extension study to evaluate the long-term safety and efficacy of ligelizumab in particiants who have completed a ligelizumab Phase III study in food allergy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Melissa.Zamudio@Childrens.com
• Signed informed consent and assent form (where applicable)
• Participants have completed the treatment period in any ligelizumab Phase III studies in food allergy
• Participants are willing to adhere to the study visits and procedures, including receiving injections and participating in the oral food challenge
• Participants agree to continue avoiding exposure to allergens (per core study) and any other foods they are allergic to throughout the study
• Participants are able to safety continue into the study as judged by the investigator
• Development of a severe or life threatening episode of an allergic reaction that required intubation and/or Intensive Care Unit admission during the core studies
• Development of a serious adverse event which is suspected to be related to the study treatment judged by the investigator during the core studies
• Development of uncontrolled asthma during the core study that could compromise the safety of participants judged by the investigator
• Development of clinically significant cardiovascular, neurological, and or psychiatric conditions during the core study that could interfere with or compromise the safety of the participants, interfere with evaluation or interpretation of the study results or preclude completion of the study judged by the investigator
• Participants who failed to comply with the protocol requirements and procedures duringthe core study, and in the Investigator's opinion they should not participate in this extension study
• Platelets <75,000/ul at end of treatment of the core study Other protocol defined inclusion/exclusion criteria may apply
Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation (JANUS)
This phase II trial compares the effect of irinotecan versus oxaliplatin after long-course chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy drugs, such as FOLFIRINOX (fluorouracil, irinotecan, leucovorin, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan ), and CAPOX (capecitabin and oxaliplatin) 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. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate and lead to higher rates of clinical complete response (with a chance of avoiding surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection (APR) or coloanal anastomosis
• Tumor site: Rectum; =< 12cm from the anal verge
• No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer within the past 5 years is allowed
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearing potential only, a negative pregnancy test (urine or serum according to institutional guidelines) done =< 14 days prior to registration is required. Female subjects agree to use highly effective contraception combined with an additional barrier method (e.g, diaphragm, with a spermicide) while on study and for >= 9 months after last dose of study drug, and the same criteria are applicable to male subjects if they have a partner of childbirth potential. Male subject agrees to use a condom and not donate sperm while in this study and for >= 6 months after the last treatment
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (or Karnofsky >= 60%)
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm
• Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 50 mL/min ^3
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• No upper rectal tumors (distal margin of tumor > 12 cm from the anal verge)
• No recurrent rectal cancer; prior transanal excision, prior distal sigmoid cancer with a low anastomosis
• No known mismatch repair deficient rectal adenocarcinoma
• Human immunodeficiency virus HIV-infected patients on effective anti-retro viral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification1. To be eligible for this trial, patients should be class 2B or better
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study * Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
FXR Effect on Severe Alcohol-Associated Hepatitis (FRESH) Study (FRESH)
The purpose of this trial is to assess dose related safety, efficacy, and pharmacokinetics (PK) of INT-787 in participants with severe alcohol-associated hepatitis (sAH).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Leticia.Rodriguez@UTSouthwestern.edu
• Males or females aged 18 to 65 years (inclusive)
• Clinical diagnosis of sAH based on all the following:
• History of ongoing excess alcohol (\>60 g/day \[male\] or \>40 g/day \[female\]) use for ≥6 months, with \<60 days of abstinence prior to the onset of jaundice
• Serum total bilirubin \>3.0 mg/dL
• Aspartate aminotransferase (AST) ≥50 U/L
• AST/Aspartate aminotransferase (ALT) ratio ≥1.5
• Onset of jaundice within prior 8 weeks
• Maddrey's Discriminant Factor (mDF) ≥32 and ≤70
• MELD score 18 to 25 (inclusive)
• Female participants must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception from the initiation of Screening and for 90 days after the last dose of investigational product as follows: * Surgical sterilization (bilateral tubal occlusion, etc.) * Placement of an intrauterine device (IUD) or intrauterine system (e.g., intrauterine hormone-releasing system \[IUS\]) * Combined (estrogen and progesterone containing) hormonal contraceptive associated with inhibition of ovulation: * Oral * Intravaginal * Transdermal * Progesterone-only hormonal contraception associated with inhibition of ovulation: * Oral * Injectable * Implantable * Sexual abstinence: Defined as avoiding all types of activity that could result in conception (pregnancy) from the initiation of Screening and until at least 90 days after the last dose of investigational product
• Male participants who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use 1 other approved method of highly effective contraception from the initiation of Screening and until at least 90 days after the dose of investigational product as listed in Inclusion Criteria #3.
• Male participants must refrain from sperm donation from the initiation of Screening and until at least 90 days after the last dose of investigational product
• Must provide written informed consent and agree to comply with the study protocol. In participants with hepatic encephalopathy which may impair decision-making, consent will be obtained per hospital procedures (e.g., by Legally Authorized Representative).
• Participants must agree to participate in an alcohol use disorder program during the study period, as recommended by the local institution's addiction medicine specialists, including post-hospitalization
• Participants taking products containing obeticholic acid in the 30 days prior to randomization
• Participants taking \>2 doses of systemic corticosteroids within 30 days prior to randomization.
• Participants who have been inpatient at a referral hospital for \>7 days prior to transfer.
• Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breast feeding.
• Abstinence from alcohol consumption for \>2 months before Day 1.
• AST or ALT \>400 U/L.
• mDF \<32 or \>70 at Screening
• MELD score \<18 or \>25 at Screening.
• Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C virus (HCV) RNA positive, drug-induced liver injury (DILI), biliary obstruction, and autoimmune liver disease.
• Current or previous history of hepatocellular carcinoma (HCC)
• History of liver transplantation or currently listed for liver transplant
• Untreated infection (e.g., has not initiated appropriate medical treatment for infection)
• Known positivity for human immunodeficiency virus infection
• Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding that was associated with shock or required transfusion of more than 3 units of blood within 7 days of Screening.
• Kidney injury defined as a serum creatinine \>133 μmol/L (\>1.5 mg/dL) or the requirement for renal replacement therapy.
• Portal vein thrombosis
• Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)
• Severe, on-going associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)
• Malignancy within the 2 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer). Participants under evaluation for possible malignancy are not eligible.
• Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, and opiates) except tetrahydrocannabinol or in the setting of documented prescription medications (e.g., opiates, benzodiazepines, amphetamines, barbiturates), which also include medications prescribed as part of in-patient management. Participants being treated for alcohol withdrawal may be exempt for this reason, verify with Medical Monitor.
• Participated in a clinical research study and received any active investigational product being evaluated for the treatment of sAH within 3 months before Day 1
• Participation in a study of another investigational medicine or device within 30 days before Screening
• Any other condition or clinical laboratory result that, in the opinion of the Investigator, might confound the results, or would impede compliance or hinder completion of the study
A Study to Investigate LYL845 in Adults With Solid Tumors
This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).
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canceranswerline@utsouthwestern.edu
A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors
This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors
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LOcoregional vs Systemic Therapy in Patients With BCLC Stage B HCC (LOST-B)
The purpose of this research study is to compare the effectiveness and safety of two standard of care treatments in people who have been diagnosed with hepatocellular carcinoma (HCC).This research study is being done to compare atezolizumab/bevacizumab to locoregional therapy with either transarterial chemoembolization (TACE) or transarterial radioembolization (TARE).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Patients with confirmed HCC by imaging (LI-RADS 5) or histopathology
• Treatment-naïve, liver localized (intermediate-stage), i.e., beyond Milan Criteria (one tumor ≤5 cm, or two to three tumors, each ≤3 cm) and not amenable to curative surgery, liver transplantation, or local ablation and no evidence of extrahepatic disease or vascular invasion.
• Child Pugh class A
• Age ≥18 years at time of screening
• ECOG Performance Status 0 or 1
• Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV NA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local lab standard) are not required to start antiviral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
• Patients with HCV infection, defined by presence of detectable antibody or RNA, should have management of this disease per local institutional practice throughout the study.
• At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria: • Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase
• Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter
• Adequate organ and marrow function at enrollment as defined below: (a) Hemoglobin ≥9.0 g/dL Patients may be transfused to meet this criterion. (b) Absolute neutrophil count ≥1500/μL (c) Platelet count ≥75000/μL (d) Total bilirubin ≤3 × the upper limit of normal (ULN) (e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN (f) Albumin ≥2.8 g/dL (g) Lymphocyte count ≥0.5 X 109/L (500/µL) (h) 2+ proteinuria or less urine dipstick reading or normal UA with less than 100 mg/dL protein (i) Calculated creatinine clearance (CL) ≥30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine CL (j) For patients not receiving therapeutic anticoagulation: INR or aPTT ≤2 × ULN
• Upper endoscopy to evaluate varices and risk of bleeding is required within one year prior to randomization
• Negative HIV test at screening
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for 6 months following completion of therapy. Women must refrain from donating eggs during this same period. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. • A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
• Chemotherapy, radiotherapy, or other cancer therapy within 3 months prior to starting study treatment.
• Any prior immunotherapy for malignancy.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Patients with infiltrative-type HCC
• Definite macrovascular invasion or distant metastatic disease at randomization
• Clinically significant ascites, requiring non-pharmacological intervention (e.g., paracentesis) to maintain control within past 6 months
• History of hepatic encephalopathy within past 6 months
• Actively listed or under evaluation for liver transplantation
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active tuberculosis
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
• History or evidence upon physical or neurological examination of central nervous system dysfuction
• Current or recent (< 10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day), or clopidogrel (> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk.
• History of leptomeningeal disease
• Uncontrolled tumor-related pain. Patients requiring pain medication should be on stable regimen prior to study entry.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus who are on an insulin are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• There is no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the 12 months prior to Day 1 of Cycle 1.
• Systemic immunostimulatory agents (including, but not limited to, IFNs and IL-2) are prohibited within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during study treatment.
• History of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
• History of grade ≥4 venous thromboembolism.
• Non-healing wound, active ulcer, or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require wound examinations every 3 weeks.
• History of abdominal fistula or GI perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment.
• History of grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within one month of screening
• Core biopsy or other minor surgical procedure, excluding vascular access device, within 7 days prior to initiation of study treatment.
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study treatment, or anticipation of need for major surgical procedure during the course of the study (Note: Biopsy and endoscopy are not considered surgery so would not be exclusion criteria)
• Uncontrolled hypertension defined by a systolic pressure >150 mmHg or diastolic pressure >90 mmHg, with or without antihypertensive medication. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
• History of allogeneic stem cell or organ transplantation
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (except for noted HBV or HCV as detailed above), symptomatic congestive heart failure, poorly controlled diabetes mellitus, unstable angina pectoris, uncontrolled cardiac arrhythmia, active Interstitial Lung Disease (ILD), serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥1 year before randomization and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• History of active primary immunodeficiency.
• Patients co-infected with HBV and hepatitis D virus (HDV). (HBV infection is defined above; HDV positive infection is indicated by the presence of anti-HDV antibodies).
• Treatment with a live, attenuated vaccine (e.g., FluMist®) within 4 weeks prior to Day 1 of Cycle 1, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab. 43 Subjects must have recovered from prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management).
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab or bevacizumab or other agents used in study.
• Subjects must not be pregnant or breastfeeding during the study treatment, or have the intention of becoming pregnant during the study treatment or within 6 months after the final dose of study treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study treatment.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of Patients who receive mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• 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.
• 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.
Colorectal Cancer Screening in Cystic Fibrosis (NICE-CF)
This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
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• Adults with CF ages 18 - 75 years and due for a routine screening or surveillance colonoscopy for colon cancer
• Cystic Fibrosis diagnosis, defined by a sweat chloride test result ≥ 60 mmol/L (may be of historic value), and/or documented CF-causing CFTR mutations and clinical features of CF
• Capable of understanding the purposes and risks of the study in English or Spanish and willing to participate and sign informed consent
• Referred for screening or surveillance colonoscopy for CRC (current standard of care) and willing to undergo colonoscopy and stool testing
• Able to access the Internet to complete self-administered surveys
• Any condition that, in the opinion of the site PI, introduces undue risk by participating in this study
• Incapable of understanding the purposes of the study or informed consent for any reason
• Pregnancy
• Active inflammatory bowel disease as defined by a prior diagnosis of Crohn's Disease or Ulcerative Colitis, based on both clinical and histopathologic findings and the individual currently on medical therapy for Crohn's disease or Ulcerative Colitis.
• Personal history of colon cancer diagnosis and treatment within 5 years of enrollment
• Symptoms that merit colonoscopy for diagnostic purposes rather than as screening for CRC
• Known history of familial colon cancer syndrome that has been confirmed by previous genetic testing
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
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• Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
• Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
• History/physical examination within 45 days prior to registration
• CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
• Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
• 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
• Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
• Patient not recommended for or refused immediate cytoreductive nephrectomy
• Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
• Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
• Age >= 18
• Karnofsky performance status >= 60 within 45 days prior to registration
• Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
• Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
• Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
• For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
• Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
• Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
• Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
• Patients with untreated or unstable brain metastases or cranial epidural disease
• Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
• Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
• Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
• Severe, active comorbidity defined as follows:
• Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
• Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
• Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
• Major surgery requiring hospital admission ≤ 28 days prior to registration.
• Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
• Active New York (NY) Heart Association class 3-4 heart failure symptoms
• Moderate or severe hepatic impairment (Child-Pugh B or C)
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
• Unstable cardiac arrhythmia within 180 days prior to registration
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
• History of or active inflammatory bowel disease
• Malabsorption syndrome within 45 days prior to registration
• Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration
Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation
This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and cetuximab) works better than the usual treatment alone to shrink tumors in patients with colorectal cancer that has spread to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF. Encorafenib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab in combination with encorafenib and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal cancer.
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Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC (EMERALD-3)
A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab, tremelimumab and lenvatinib therapy in patients with locoregional hepatocellular carcinoma
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• No evidence of extrahepatic disease
• Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE
• Child Pugh score class A
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria
• Adequate organ and marrow function
• History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardia arrhythmia
• History of hepatic encephalopathy
• Major portal vein thrombosis visible on baseline imaging
• Uncontrolled arterial hypertension
• Co-infection with HBV and HDV
A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma
This study is a Phase 1b/2, dose-escalation, randomized, multicenter study to assess the efficacy, safety, tolerability, and PK of ivaltinostat in combination with capecitabine and capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease has not progressed on a first line fluoropyrimidine-based chemotherapy (e.g., FOLFIRINOX). In Phase 1b, 3 dose levels of ivaltinostat will be studied in combination with a fixed dose of capecitabine to determine the RP2D of ivaltinostat. In Phase 2, patients will be randomized in a 1:1 ratio to the combination of ivaltinostat and capecitabine or to capecitabine monotherapy. A fixed dose for capecitabine 1000 mg/m2 orally twice daily will be taken on Days 1 to 14, and the RP2D of ivaltinostat will be administered intravenously once a week for 2 weeks, followed by 1 week of rest. One cycle consists of 21 days. Tumor response during study treatment will be assessed every 6 weeks up to Cycle 10, then every 9 weeks afterwards using RECIST v1.1 criteria.
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Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis (LIVERATION)
This is a clinical trial in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B7 (CPB7) cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo.
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• Males and females at least 18 years of age.
• Diagnosis of HCC:
• For patients without cirrhosis at the time of diagnosis, histologic confirmation is required (archival tissue is acceptable).
• For patients with underlying cirrhosis at the time of diagnosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Marrero 2018).
• HCC is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
• HCC has progressed on at least 1, but no more than 2, prior systemic treatment regimens; prior locoregional therapy is allowed.
• Barcelona Clinic Liver Cancer (BCLC) Stage B or C (Llovet 1999).
• Prior HCC treatment was discontinued for at least 2 weeks prior to the Baseline Visit.
• Measurable disease by RECIST v1.1 (Eisenhauer 2009).
• ECOG PS of ≤ 1.
• Cirrhosis classified as CPB7; if ascites is used as a scoring criterion, it must be classified as Grade ≥2 by the Clinical Practice Guidelines of the European Association for the Study of the Liver (EASL 2010).
• The following laboratory values must be documented within ten days prior to the first dose of study drug:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count at least 75 × 10^9/L
• Creatinine clearance at least 50 mg/dL (estimated glomerular filtration rate by the Cockcroft-Gault or the Modification of Diet in Renal Disease methods)
• AST and ALT ≤ 5 × the upper limit of normal (ULN)
• Total bilirubin ≤ 3.0 mg/dL
• Serum albumin ≥ 2.8 g/dL.
• Life expectancy of ≥ 6 weeks.
• For women of childbearing potential, negative serum pregnancy test result.
• Provide written informed consent to participate.
• Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures.
• Receipt of >2 prior systemic drug therapies for HCC.
• Receipt of systemic cancer therapy, immunomodulatory drug therapy, immunosuppressive therapy, or corticosteroids > 20 mg/day prednisone or equivalent within 14 days prior to the Baseline Visit or concurrently during the trial.
• Locoregional treatment within 4 weeks prior to the Baseline Visit.
• Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.
• Use of any investigational agent within 4 weeks prior to the Baseline Visit.
• Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product (see Section 12.2).
• Child-Pugh Class A, B8/9, or C cirrhosis.
• Hepatic encephalopathy.
• Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
• Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
• Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
• Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
• Liver transplant.
• Active malignancy other than HCC.
• Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4).
• Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
• History of, or ongoing, cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 470 msec (patients with bundle branch block will not be excluded for QTc reasons).
• Pregnant or lactating female.
• Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient's circumstances while on study drug.
• Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
• Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with trial participation or study drug administration; may interfere with the informed consent process and/or with compliance with the requirements of the trial; or may interfere with the interpretation of trial results and, in the Investigator's opinion, would make the patient inappropriate for entry into this trial.