Cabozantinib in Hepatocellular Carcinoma

Sponsor
Stephen Chan Lam
Study ID
NCT04588051
Phase
PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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

Key Dates

First listed
Oct 19, 2020
Start date
Nov 1, 2020
Status verified
Mar 2026
Primary completion
Dec 31, 2027
Completion
Dec 31, 2028

Study Design

Enrollment
20 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Cabozantinib

Primary Outcome Measure

Median Progression-free survival (PFS) [ Time Frame: 1 year ]

Find similar trials

Nationwide
Liver cancer trialsOncology trialsGI oncology trialsHepatology trials

Related Studies