A Phase II Study to Evaluate the Effects of Sequential Therapy With the Anti c-MET/VEGFR Tyrosine Kinase Inhibitor (TKI), Cabozantinib, Followed by an Anti-PD-1 Antibody (Nivolumab) in Patients With Advanced HCC Who Progressed on First-line Therapy

Phase 2

Withdrawn

• Conditions: Liver Cancer; Hepatocellular Carcinoma
• Interventions: Drug: Cabozantinib; Drug: Nivolumab

• Registration Number: NCT05039736
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

The purpose of this clinical research study is to learn about the safety and effectiveness of cabozantinib and nivolumab in people with hepatocellular carcinoma (HCC).

Detailed Description

Primary objective is to evaluate overall response rate

Secondary objectives are to evaluate progression-free survival and overall survival

Exploratory endpoints

To explore the association between c-MET, PD-1/PD-L1 (and PD-L2) expression by immunohistochemistry, RNA seq genomic profiling and antitumor efficacy of nivolumab

+ cabozantinib based on RECIST 1.1 To evaluate correlation between fibrosis stage by histology, by magnetic resonance elastography (MRE) imaging and by IGF1 scores To evaluate baseline and longitudinal changes of blood and tumor markers such as TNFα, pSTAT3, and EGFR, immune cell density including frequency of PD-1 + 4-1BB + CD8+ T cells, pro-inflammatory cytokines, and hepatic fibrosis markers (APRI, FIB-4, hyaluronic acid, FibroTest \[FibroSure\], nonalcoholic fatty-liver disease fibrosis score, enhanced liver fibrosis \[ELF\]) test as biomarkers of response to therapy To evaluate candidate serum and tissue biomarkers to predict response to cabozantinib (e.g. Kallikrein 5, KLK-7, MCP-1, LAP/TGF-β1, Galectin-3) and nivolumab (e.g. angiogenin, Endostatin, PGI, PAI-1, Cystatin-B, CD8 T cell frequency and Ki67) To evaluate the predictive value of dynamic changes in fibrosis stage (defined by a minimum 2-point improvement in fibrosis grade 0-4 per MRE) and in IGF-1 blood scores

Study Timeline

• Study First Submitted: 2021-09-01
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-10
• Study Start: 2023-02-24
• Status Verified: 2023-05
• Primary Completion: 2023-05-03
• Study Completion: 2023-05-03
• Last Update Submitted: 2023-05-10
• Last Update Posted: 2023-05-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cabozantinib	Cabozantinib	cabozantinib by mouth every day for 6 weeks
nivolumab	Nivolumab	nivolumab by vein every 4 weeks for up to 2 years

Primary Outcome Measures

Name	Time	Method
To evaluate overall response rate	through study completion, an average of 1 year