Status:
WITHDRAWN
Lenvatinib Plus Nivolumab Versus Lenvatinib for Advanced Hepatocellular Carcinoma With Hepatitis B Virus Infection
Lead Sponsor:
Shi Ming
Collaborating Sponsors:
First Affiliated Hospital, Sun Yat-Sen University
Guangzhou No.12 People's Hospital
Conditions:
Hepatocellular Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
PHASE3
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 hep...
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 carcinom...
Eligibility Criteria
Inclusion
- 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\<=1.
- At least one tumor lesion that can be accurately measured according to the RECIST 1.1
- ECOG Performance Status of 0 or 1
- No cirrhosis or cirrhotic status of Child-Pugh class A only. Documented virology status of HBV, as confirmed by screening HBV serology test, as evidenced by detectable HBV surface antigen. (there is no lower and upper limit of HBV DNA, but patients must be on effective antiviral therapy if HBV DNA is positive \[greater than zero\]).
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior torandomization, unless otherwise specified:
- white blood cell count ≥ 3.0×10⁹ per L
- absolute neutrophil count ≥ 1.5×10⁹ per L
- platelet count ≥ 75×10⁹ per L
- Hemoglobin ≥ 8.5 g/dL
- Prothrombin time (PT)-international normalized ratio (INR) ≤ 2.3 or Prothrombin time (PT) ≤ 6 seconds above control
- total bilirubin ≤ 30mmol/L
- serum albumin ≥ 30 g/L
- aspartate transaminase and alanine transaminase ≤ 5×upper limit of the normal
- creatinine clearance of ≤1.5×upper limit of the normal or a creatinine clearance \> 50 mL/min (Cockcroft-Gault formula)
- left ventricular ejection fraction (LEVF) ≥45% as measured by echocardiography
- Reproductive status: Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within one day prior to the start of study drug. Women must not be breastfeeding.
Exclusion
- 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
- Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 30 days of study administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease
- Treatment with anti-platelet therapy (aspirin at dose\>=300 mg/day, clopidogrel at dose\>=75 mg/day) or current anticoagulation therapy
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways)
- All toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae are permitted to enroll. Neuropathy must have resolved to Grade 2 (NCI CTCAE version 4.03).
- Known central nervous system tumors including metastatic brain disease
- Patients who are pregnant or breastfeeding. Women with a positive pregnancy test at enrollment or prior to administration of study medication
- Other invasive malignant diseases
- Prisoners, or subjects who are compulsory detained
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Key Trial Info
Start Date :
October 30 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 30 2022
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT04044651
Start Date
October 30 2019
End Date
September 30 2022
Last Update
January 9 2020
Active Locations (5)
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1
Cancer Center Sun Yat-sen University
Guangzhou, Guangdong, China, 510060
2
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China, 510060
3
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China, 510060
4
The Third Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China, 510060