NCT05039736

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

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Conditions

• Hepatocellular Carcinoma
• Liver Cancer

Interventions

Type	Name	Description
DRUG	Cabozantinib	Given by PO
DRUG	Nivolumab	Given by IV

Timeline

• Start date: 2023-02-24
• Primary completion: 2023-05-03
• Completion: 2023-05-03
• First posted: 2021-09-10
• Last updated: 2023-05-12

Regulatory

• FDA-regulated drug study