None listed
Conditions
Interventions
Drug : This study is a multicenter, non-comparative, phase II clinical trial designed to evaluate the efficacy and safety of subsequent treatment with lenvatinib and regorafenib in patients with advan
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Diagnosis of hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) guidelines (Appendix 1). 2) Unresectable HCC for which curative treatments such as surgery, liver transplantation, or radiofrequency ablation are not feasible. 3) Patients who have received first-line systemic therapy with a standard immune checkpoint inhibitor (ICI)–based combination regimen for advanced HCC (e.g., atezolizumab plus bevacizumab, STRIDE [durvalumab plus tremelimumab], or nivolumab plus ipilimumab). - Participation is allowed even if the patient received these agents as part of another clinical trial. (Note: For the REVIVE-1 cohort, only patients who received a dual ICI–based combination as first-line therapy are eligible.) 4) Radiologic disease progression after at least two cycles of prior ICI-based combination therapy. 5) At least one measurable lesion according to RECIST version 1.1. (This criterion applies only to the REVIVE-1 cohort; it is not mandatory for REVIVE-2.) 6) All toxicities related to prior therapy have resolved to Grade =1 (CTCAE v5.0), except for clinically non-significant or stable toxicities under optimal supportive management. 7) Estimated life expectancy of at least 12 weeks. 8) Age =19 years at the time of informed consent. 9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10) Adequate hematologic function: A. Absolute neutrophil count (ANC) = 1.0 × 10?/L B. Platelet count = 75 × 10?/L (REVIVE-1) or = 50 × 10?/L (REVIVE-2) C. Hemoglobin = 9 g/dL 11) Adequate renal function: A. Serum creatinine = 1.5 × upper limit of normal (ULN) or creatinine clearance = 40 mL/min (calculated by the Cockcroft–Gault equation), and B. Proteinuria 480 ms is observed, two additional ECGs should be performed approximately 3 minutes apart within 30 minutes of the first measurement, and the mean QTcF of the three recordings must be = 480 ms for enrollment. 16) Ability to understand and comply with the study requirements, and provision of written informed consent prior to any study-specific procedures. 17) Female patients of childbearing potential must have a negative pregnancy test at screening, and all subjects of reproductive potential (male and female) must agree to use effective contraception throughout the study and for at least 4 months after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1) Known diagnosis of fibrolamellar carcinoma or combined hepatocellular–cholangiocarcinoma. 2) Prior treatment with lenvatinib or regorafenib. 3) Patients who have received two or more prior systemic anticancer therapies (i.e., lenvatinib or regorafenib must be administered as second-line treatment). 4) Known brain metastases or epidural disease. - Exception: Patients adequately treated with radiotherapy and/or surgery (including stereotactic radiosurgery) and radiologically stable for =3 months prior to enrollment are eligible. 5) Uncontrolled, clinically significant comorbidities or recent illnesses, including but not limited to the following: A. Cardiovascular and cardiac disorders i. Clinically significant cardiovascular disease such as congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to first study drug administration, or any clinically significant cardiac arrhythmia requiring treatment at screening. ii. Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg) despite optimized antihypertensive therapy. iii. Thrombotic or bleeding disorders associated with significant hemorrhagic risk (including uncontrolled anticoagulant therapy such as unstable INR or a history of severe bleeding). iv. Tumor invasion or encasement of major vessels (e.g., carotid artery) that may pose a risk of severe hemorrhage due to tumor shrinkage or necrosis following lenvatinib or regorafenib therapy. B. Gastrointestinal disorders with a high risk of perforation, fistula, or bleeding, including but not limited to: i. Tumor invasion of the gastrointestinal tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, pancreatic or biliary obstruction, or gastric outlet obstruction. ii. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months prior to enrollment. 6) Major surgery within 2 months prior to enrollment, incomplete wound healing at the time of screening, or ongoing clinically significant postoperative complications. 7) Moderate or severe ascites (radiographically detectable but clinically insignificant ascites is permitted). 8) History of allergy or hypersensitivity to lenvatinib, regorafenib, or any excipients of the study drugs. 9) Pregnant or breastfeeding women at screening or baseline. 10) Diagnosis of another malignancy requiring active treatment within 2 years prior to enrollment, except for adequately treated superficial skin cancer or localized, low-grade tumors considered cured without systemic therapy. 11) Uncorrected electrolyte abnormalities. 12) Failure to adequately recover from toxicities related to prior anticancer therapy and/or from complications of major surgery prior to initiation of study treatment. 13) Any other clinically significant medical condition that, in the investigator’s judgment, would make the patient unsuitable for participation in this study. 14) Clinically symptomatic hypothyroidism at the time of screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) according to RECIST v1.1;Overall survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Toxicity Profile;Response rate;Time to liver function deterioration (TLD) | — |
Countries
Korea, Republic of
Contacts
Public ContactChanghoon Yoo
Asan Medical Center
Outcome results
None listed