Ignite Creation Date:
2025-12-24 @ 9:32 PM
Ignite Modification Date:
2025-12-25 @ 7:17 PM
Study NCT ID:
NCT05134532
Status:
UNKNOWN
Last Update Posted:
2023-04-26
First Post:
2021-11-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Regorafenib After Progression on Atezolizumab Plus Bevacizumab in Advanced HCC
Sponsor:
CHA University
Organization:
Study Overview
Official Title:
Phase II Trial of Regorafenib in Patients With Unresectable Hepatocellular Carcinoma After Progression on First Line Atezolizumab Plus Bevacizumab (REGONEXT Trial)
Status:
UNKNOWN
Status Verified Date:
2023-04
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
HCC
Brief Summary:
To investigate efficacy and toxicity of regorafenib after treatment with atezolizumab and bevacizumab combination
Detailed Description:
* There is preclinical and clinical data on synergistic activity of angiogenesis inhibitors and anti-programmed death-1 (anti-PD-1) targeted therapy. Targeting VEGFR decreased T-regulatory cells and Myeloid-derived suppressor Cells. In addition, VEGF-A produced in the tumor microenvironment enhanced expression of PD-1 involved in CD8 T cell exhaustion8. The combination of targeted therapy and immune-checkpoint inhibitors (ICIs), either in a parallel or sequential manner, could theoretically lead to enhanced anti-tumor responses, reflected in durable responses and prolonged survival. However, there have been lack of clinical data of targeted agents who developed progressive disease with ICIs.
* In previous phase I study, pharmacodynamics indicated a sustained occupancy of \> 70% of PD-1 molecules on circulating T-cells ≥ 2 months following infusion. Based on these findings, ICI use may retain the prolonged effect even after discontinuation. There was a case report of a sorafenib-refractory patient experiencing progressive disease during ICI combination treatment with the anti-PD-1 antibody and the anti-GITR antibody within phase I trial followed by a prolonged tumor response during third-line regorafenib monotherapy.
* In patients with advanced HCC, anti-VEGF monoclonal antibodies, multi-kinase inhibitor (sorafenib, regorafenib, cabozantinib and lenvatinib) and ICIs are available treatment options, however, treatment sequencing and combination strategy are challenging.
* Atezolizumab plus bevacizumab demonstrated survival benefit and established as a new first-line therapy, hence it is clinically important to study the efficacy and toxicity of regorafenib after treatment with ICIs or ICI combination.
* In previous phase I study, pharmacodynamics indicated a sustained occupancy of \> 70% of PD-1 molecules on circulating T-cells ≥ 2 months following infusion. Based on these findings, ICI use may retain the prolonged effect even after discontinuation. There was a case report of a sorafenib-refractory patient experiencing progressive disease during ICI combination treatment with the anti-PD-1 antibody and the anti-GITR antibody within phase I trial followed by a prolonged tumor response during third-line regorafenib monotherapy.
* In patients with advanced HCC, anti-VEGF monoclonal antibodies, multi-kinase inhibitor (sorafenib, regorafenib, cabozantinib and lenvatinib) and ICIs are available treatment options, however, treatment sequencing and combination strategy are challenging.
* Atezolizumab plus bevacizumab demonstrated survival benefit and established as a new first-line therapy, hence it is clinically important to study the efficacy and toxicity of regorafenib after treatment with ICIs or ICI combination.
Study Oversight
Has Oversight DMC:
False
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?: