Clinical Trials /

Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma

NCT03382886

Description:

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).

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
  • Official Title: A Phase I Open Label Trial of a Combination of Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: HCI103945
  • NCT ID: NCT03382886

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
NivolumabOPDIVONivolumab and bevacizumab, all patients
BevacizumabNivolumab and bevacizumab, all patients

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and bevacizumab, all patientsExperimental
  • Nivolumab
  • Bevacizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events that occur
Time Frame:Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:3 years after treatment stops
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:3 years after treatment stops
Safety Issue:
Description:To examine the effect of the study treatment combination on the rate of overall survival.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Utah

Trial Keywords

  • Advanced and/or metastatic

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