Trials / Completed

CompletedNCT03439891

Sorafenib and Nivolumab in Treating Participants With Unresectable, Locally Advanced or Metastatic Liver Cancer

Multicenter Pilot Study of the Safety, Efficacy, and Immune Cell Profiling in Advanced Hepatocellular Carcinoma (HCC) Patients Treated With the Combination of Sorafenib Plus Nivolumab as First-Line of Systemic Therapy

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 16 (actual)

Sponsor: Robin Kate Kelley · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies the best dose and side effects of sorafenib tosylate and nivolumab in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to nearby tissues or lymph nodes (locally advanced) or to other places in the body (metastatic). Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sorafenib tosylate and nivolumab may work better in treating patients with liver cancer.

Detailed description

PRIMARY OBJECTIVES: I. Maximum tolerated dose (MTD) of sorafenib tosylate (sorafenib) in combination with standard dose nivolumab with Child Pugh A-B7 liver function. (Part 1: Escalation Cohort). II. Safety in participants with Child-Pugh B liver function. (Part 2: Child-Pugh B Escalation Cohort) SECONDARY OBJECTIVES: I. Safety and tolerability of combination overall. (Parts 1 and 2). II. Rate of immune-related adverse event (irAE) for combination overall and in participants with Child-Pugh B liver function. (Parts 1 and 2). III. Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in participants with Child-Pugh B liver function. (Parts 1 and 2). IV. Duration of response (DOR), progression free survival (PFS), and overall survival (OS) for escalation cohort and Child-Pugh B expansion cohort and overall. (Parts 1 and 2). EXPLORATORY OBJECTIVES: I. Relationship between peripheral blood mononuclear cell (PBMC) immune cell subset frequencies, baseline liver function, and clinical outcomes. II. Relationship between PBMC T cell receptor (TCR) clonotype frequency and diversity, baseline liver function, and clinical outcomes. III. Tumor tissue immune cell subsets and TCR clonotype frequency and diversity in pre-treatment archival tumor tissue samples. IV. Tumor and immune cell programmed death-ligand 1 (PD-L1) status in pre-treatment archival tumor tissue samples and relationship to clinical outcomes. V. Changes in hepatitis B virus (HBV) and/or hepatitis C virus (HCV) viral load on treatment. VI. Alpha-fetoprotein (AFP) changes on treatment and relationship to clinical outcomes. VII. Relationship between clinical outcomes and clinicopathologic features including race/ethnicity, etiology of liver disease including HBV/HCV status, baseline liver function, presence of cirrhosis, macrovessel invasion, extrahepatic spread, site(s) of metastatic disease, prior treatment history including prior radiation and arterial therapies. OUTLINE: This is a dose-escalation and expansion study of sorafenib tosylate. DOSE-ESCALATION (Part 1): Between 3-12 participants will be enrolled in Part 1. Participants receive sorafenib tosylate orally (PO) once daily (QD) or twice daily (BID) on days 1-28, and nivolumab intravenously (IV) over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. EXPANSION COHORT (Part 2). Participants receive nivolumab IV over 30 minutes on days 1 and 15, and sorafenib tosylate once daily (QD) or twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 and 100 days, then every 3 months for up to 2 years after the last dose.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Nivolumab	Given IV
DRUG	Sorafenib	Given PO

Timeline

Start date: 2018-04-16
Primary completion: 2023-11-30
Completion: 2023-11-30
First posted: 2018-02-20
Last updated: 2025-02-11
Results posted: 2025-02-11

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03439891. Inclusion in this directory is not an endorsement.