Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
- Registration Number
- NCT03382886
- Lead Sponsor
- University of Utah
- Brief Summary
This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of the combination of nivolumab and bevacizumab. The study will use a 3+3 phase I study design using a fixed dose of nivolumab (240mg) and escalating doses of bevacizumab (1-10mg).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
Inclusion Criteria
- Confirmed unresectable or metastatic hepatocellular carcinoma. Confirmation either by histologic confirmation or accepted radiographic criteria.
- Received at least one line of therapy with a TKI (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI. No more than two lines of prior therapy are allowed.
- Measurable disease per RECIST1.1.
- Age ≥18 years.
- ECOG performance status of 0 to 1.
- Life expectancy ≥ 12 weeks.
- Childs Pugh A (5-6 points). Demonstrate adequate organ function as defined in the table below
Hematologic:
Absolute neutrophil count (ANC) ≥ 1.5 k/µL. Platelets ≥ 100 k/µL Hemoglobin ≥ 9 g/dL
Renal:
Creatinine < 2 × ULN OR
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
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Exclusion Criteria
- Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy.
- Subjects with a prior history of DVT/PE, who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks.
- History of arterial thromboembolic event in past 6 months (including CVA, MI).
- Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade ≤1.
- Radiotherapy within 2 weeks of first dose of study medications.
- Major surgery within 6 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 4 weeks of first dose of study medications.
- Presence of ≥ CTCAE grade 2 toxicity due to prior cancer therapy (except alopecia, peripheral neuropathy which are excluded if ≥ CTCAE grade 3).
- Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
- Active ongoing infection requiring therapy.
- Active HIV infection.
- History of severe hypersensitivity reaction to another monoclonal antibody.
- Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids >4 weeks allowed).
- Cardiac conditions: class 3-4 New York Heart Association congestive heart failure, known baseline LVEF < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months.
- Any history of autoimmune disease requiring treatment in the past 5 years or felt to be at risk to reactivate autoimmune disease. Patients who are felt to no longer be at risk of activating a known autoimmune disease (e.g. type 1 diabetes, ulcerative colitis s/p complete colectomy, autoimmune thyroiditis s/p thyroidectomy or medical ablation, etc.) may be allowed to participate after discussion with the PI
- Pregnant, breast feeding, or planning to become pregnant.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Received any live vaccine within the last 30 days.
- Other malignancy requiring treatment in the prior 2 years with the exception of locally treated squamous or basal cell carcinoma.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab and bevacizumab, all patients Nivolumab - Nivolumab and bevacizumab, all patients Bevacizumab -
- Primary Outcome Measures
Name Time Method Adverse Events that occur Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months Investigate the safety and tolerability of 14-day cycles of nivolumab plus bevacizumab.
Adverse events will be collected for each subject that received the study treatment combination.Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 3 years after treatment stops To examine the effect of the study treatment combination on the rate of progression-free survival (PFS).
Subjects will have regular imaging scans to measure disease status and response will be defined by RECIST1.1.Overall Survival 3 years after treatment stops To examine the effect of the study treatment combination on the rate of overall survival.
Trial Locations
- Locations (1)
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States