The goal of this clinical trial is to learn if lenvatinib or regorafenib can help treat people with advanced liver cancer (hepatocellular carcinoma, HCC) that cannot be removed with surgery after first treatment with immunotherapy-based drug combinations. It will also look at the safety of these treatments.
The main questions this study aims to answer are:
* How long lenvatinib can delay cancer growth in people with good liver function (Child-Pugh)A after dual immunotherapy * How long people with reduced liver function (Child-Pugh B7-B8) live after treatment with lenvatinib or regorafenib after first-line immunotherapy-based combination treatment * What side effects people experience during treatment * How many people have their tumors shrink or disappear
The study has two parts:
In REVIVE-1, participants with Child-Pugh A liver function will receive lenvatinib.
In REVIVE-2, participants with Child-Pugh B7 to B8 liver function will receive either lenvatinib or regorafenib.
Participants will:
* take lenvatinib or regorafenib by mouth * visit the clinic regularly for physical exams, blood and urine tests, and safety checks * have computed tomography (CT) scans every 8 weeks to check their cancer * be followed during and after treatment to assess outcomes and side effects
Age 19 years or older
Diagnosis of hepatocellular carcinoma according to the American Association for the Study of Liver Diseases (AASLD) guidelines
Unresectable or metastatic hepatocellular carcinoma not amenable to curative treatments such as surgical resection, liver transplantation, or local ablation
Prior first-line systemic treatment with an immune checkpoint inhibitor-based combination regimen, defined as dual immune checkpoint inhibitor therapy (e.g., nivolumab plus ipilimumab or durvalumab plus tremelimumab) for the REVIVE-1 cohort, and immune checkpoint inhibitor-based combination therapy (e.g., atezolizumab plus bevacizumab, durvalumab plus tremelimumab, nivolumab plus ipilimumab, camrelizumab plus rivoceranib, or similar regimens) for the REVIVE-2 cohort; prior participation in clinical trials using these regimens is allowed
Known fibrolamellar hepatocellular carcinoma or mixed hepatocellular-cholangiocarcinoma
Prior treatment with lenvatinib or regorafenib
Receipt of two or more prior systemic treatment regimens for advanced hepatocellular carcinoma
Known brain metastases or epidural disease unless adequately treated and clinically stable for at least 3 months
Parallel
Lenvatinib
DrugLenvatinib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), platelet-derived growth factor receptor alpha (PDGFR-α), RET, and KIT. In this study, lenvatinib is administered orally as second-line treatment according to protocol-defined dosing based on liver function and body weight.
regorafenib
DrugRegorafenib is an oral multikinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases including VEGFR, FGFR, PDGFR, KIT, RET, and RAF kinases. In this study, regorafenib is administered orally as second-line treatment according to protocol-defined dosing.
Progression-Free Survival (PFS) in REVIVE-1
Progression-free survival is defined as the time from first dose of study treatment to disease progression according to RECIST v1.1 or death from any cause, whichever occurs first, in the REVIVE-1 cohort.
Overall Survival (OS) in REVIVE-2
Overall survival is defined as the time from first dose of study treatment to death from any cause in the REVIVE-2 cohort.
Overall Survival (OS) in REVIVE-1
Overall survival is defined as the time from first dose of study treatment to death from any cause in the REVIVE-1 cohort.
Progression-Free Survival (PFS) in REVIVE-2
Progression-free survival is defined as the time from first dose of study treatment (lenvatinib or regorafenib) to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first, in the REVIVE-2 cohort.
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of participants who achieve a confirmed complete response or partial response according to RECIST v1.1. in both REVIVE-1 and REVIVE-2 cohorts.
Incidence of Treatment-Emergent Adverse Events
The incidence and severity of treatment-emergent adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in both REVIVE-1 and REVIVE-2 cohorts.
Click on the lead sponsor to view all of their trials.
Asan Medical Center
Lead sponsor
Korean Cancer Study Group
Collaborator
Boryung Pharmaceutical Co., Ltd
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
