Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma (NUANCE)

Utah System of Higher Education (USHE)

Status and phase

Terminated

Phase 1

Conditions

Hepatocellular Carcinoma

Treatments

Drug: Nivolumab

Drug: Bevacizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03382886

HCI103945

Details and patient eligibility

About

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).

Enrollment

1 patient

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.