A Randomized, Phase IIb Study of Lenvatinib Plus Nivolumab Versus Lenvatinib for Advanced Hepatocellular Carcinoma (HCC) With Hepatitis B Virus (HBV) Infection
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Shi Ming
- Locations
- 5
- Primary Endpoint
- Overall survival (OS)
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to investigate the efficacy and safety of lenvatinib plus nivolumab compared with lenvatinib monotherapy for patients with advanced hepatitis B virus infection-related hepatocellular carcinoma.
Detailed Description
Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and nivolumab was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated the efficacy and safety of lenvatinib plus nivolumab compared with lenvatinib monotherapy. Thus, the investigators carried out this prospective, randomized, phase IIb study to find out it.
Investigators
Shi Ming
Proffessor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Patients who meet all of the following criteria in screening tests and observations within 14 days before enrollment will be included in the study.
- •Signed Informed Consent Form
- •Males and Females, 18 years or older at time of signing Informed Consent Form
- •Ability to comply with the study protocol, in the investigator's judgment
- •HCC with diagnosis confirmed by histology/cytology by AASLD criteria
- •Barcelona clinic liver cancer (BCLC) C stage.
- •No prior systemic therapy for HCC
- •Patients must not be appropriate for surgery or loco-regional therapy. Patients can receive no previous anti-cancer therapy or have progressed or have intolerable adverse events after surgery or loco-regional therapy. Surgery or locoregional therapy include hepatic resection, ablation, transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiotherapy, and must have been completed at least 4 weeks (washout period) prior to the baseline scan. In addition, all acute toxic effects of the locoregional procedure must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade\<=
- •At least one tumor lesion that can be accurately measured according to the RECIST 1.1
- •ECOG Performance Status of 0 or 1
Exclusion Criteria
- •Patients who meet one of the following criteria in screening tests and observations before enrollment will be excluded from the study:
- •Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC was excluded.
- •Any history of hepatic encephalopathy
- •Any prior (within 30 days) or current clinically significant gastrointestinal bleeding or clinically significant ascites as measured by physical examination and that requires active paracentesis for control
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Known history of hepatitis C virus (HCV) or hepatitis D virus (HDV) infection
- •Active bacterial or fungal infections requiring systemic treatment within 7 days prior to study drug dosing
- •Prior organ allograft such as liver transplant, etc. or allogeneic bone marrow transplantation
- •Known or suspected allergy to the investigational agents or any agent given in association with this trial
- •Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement. psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Arms & Interventions
Lenvatinib plus nivolumab
nivolumab 480 mg IV infusions for 30 minutes q4w+ lenvatinib 12 mg (or 8 mg) by mouth (Po) once daily
Intervention: Lenvatinib
Lenvatinib plus nivolumab
nivolumab 480 mg IV infusions for 30 minutes q4w+ lenvatinib 12 mg (or 8 mg) by mouth (Po) once daily
Intervention: Nivolumab
Lenvatinib
Lenvatinib 12 mg (or 8 mg) Po once daily
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: 18 months
OS is the length of time from the date of randomization until death from any cause. The date survival was last confirmed will be used to censor surviving patients. In the absence of confirmation of death, the survival time will be censored at the last date the patient was known to be alive or at the cutoff date, whichever comes first. Unfollowable patients will be censored by the date survival was last confirmed before they became unfollowable.
Secondary Outcomes
- Objective response rate (ORR)(18 months)
- Progression free survival (PFS)(18 months)
- Duration of response (DOR)(18 months)
- Adverse event(18 months)
- OS stratified according to degree of PVTT (Vp0-3 vs Vp4)(18 months)