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

NCT03382886 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HCI103945
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatocellular Carcinoma

Keywords

Advanced and/or metastatic

Outcome Measures

Primary Outcomes (2)

• Adverse Events that occur

  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.

  Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months

• Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

  Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation

  The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  3 years after treatment stops

• Overall Survival

  3 years after treatment stops

Study Arms (1)

Nivolumab and bevacizumab, all patients

EXPERIMENTAL

Drug: Nivolumab; Drug: Bevacizumab

Interventions

Nivolumab DRUG

Nivolumab will be administered as a 240mg IV infusion given once every two weeks (+/- 3 days). Subjects will remain on study treatment for up to two years or until progression or excessive toxicity

Also known as: OPDIVO

Nivolumab and bevacizumab, all patients

Bevacizumab DRUG

Bevacizumab will be administered as an IV infusion from 1-10mg/kg in accordance with the appropriate subject cohort being examined as described below: Dose level 1: 5 mg/kg intravenously once every two weeks Dose level 2: 10 mg/kg intravenously once every two weeks Dose level -1: 1 mg/kg intravenously once every two weeks Dosing is based on actual body weight. There is no dose adjustment for obese or frail individuals. Dosing is recalculated if patient weight changes by more than 10% as reviewed by the principal investigator. Subjects will remain on study treatment for up to two years or until progression or excessive toxicity

Nivolumab and bevacizumab, all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Glynn W Gilcrease, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D)

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: April 11, 2018
• Primary Completion: July 26, 2018
• Study Completion: July 2, 2019
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

US (1)