Ignite Creation Date:
2024-05-06 @ 3:18 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04588051
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-07-28
First Post:
2020-10-07
Brief Title:
Cabozantinib in Hepatocellular Carcinoma
Sponsor:
Stephen Chan Lam
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
A Phase II Clinical Trial to Study the Efficacy of Cabozantinib in Patients With Hepatocellular Carcinoma Refractory to Checkpoint Inhibitors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 HGFc-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
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 HGFc-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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None