nivolumab and bevacizumab in patients with advanced and or metastatic hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma

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).


Eligibility criteria:
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. 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.

Keywords: advanced and/or metastatic