NCT04588051

Cabozantinib in Hepatocellular Carcinoma

A Phase II Clinical Trial to Study the Efficacy of Cabozantinib in Patients With Hepatocellular Carcinoma Refractory to Checkpoint Inhibitors

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Stephen Chan Lam · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

There have been lack of clinical studies on the role of drug treatment in patients who develop progressive disease with immune checkpoint inhibitors. Amongst HCC patients who become intolerant or refractory to sorafenib, cabozantinib has been shown by phase III clinical trial (CELESTIAL) to prolong the overall survival of patients, as compared to placebo. It is expected more patients will be treated with immune checkpoint inhibitors in future, hence it is clinically important to study the efficacy and toxicity of cabozantinib after treatment with immune checkpoint inhibitors. Further, both MET activation and upregulation of regulatory T cells are implicated in resistance mechanism to immune checkpoint inhibitors. Immuno-modulatory effects of cabozantinib have been described in vitro and in murine models for several cancers. Moreover, cabozantinib appears to exert its effect on regulatory T cells (Tregs) via the HGF/c-Met pathway, where this receptor signaling cascade mediates multiple immune cell functions. HGF was shown to suppress DC function and in turn induce Tregs (CD4+ CD25+ FoxP3) in a murine central nervous system (CNS) autoimmunity model. HGF cultured monocytes differentiate into monocytic cells that produce soluble factors that favor immune suppressive conditions ideal for tumor progression. Above immunomodulatory effects could enable cabozantinib to reverse the immunosuppressive phenotype in patients after failure with immune checkpoint inhibitors. The starting dose of cabozantinib of 60mg once daily in the current study is chosen in accordance with approved dose by FDA for treatment of advanced HCC

Conditions

• HCC

Interventions

Type	Name	Description
DRUG	Cabozantinib	60mg daily

Timeline

• Start date: 2020-11-01
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2020-10-19
• Last updated: 2026-03-04

Locations

2 sites across 2 countries: Hong Kong, South Korea