Lenvatinib Plus Nivolumab Versus Lenvatinib for Advanced Hepatocellular Carcinoma With Hepatitis B Virus Infection

NCT04044651 | Withdrawn Phase 2 DMC

• 1 other identifier: HCC-S051
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Lenvatinib; Nivolumab; Hepatitis B virus

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  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.

  18 months

Secondary Outcomes (5)

• 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

Other Outcomes (9)

• Disease control rate (DCR)

  18 months

• Time to progression (TTP)

  18 months

• Time to response (TTR)

  18 months

Study Arms (2)

Lenvatinib plus nivolumab

EXPERIMENTAL

nivolumab 480 mg IV infusions for 30 minutes q4w+ lenvatinib 12 mg (or 8 mg) by mouth (Po) once daily

Drug: Lenvatinib; Drug: Nivolumab

Lenvatinib

ACTIVE COMPARATOR

Lenvatinib 12 mg (or 8 mg) Po once daily

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

lenvatinib 12 mg (or 8 mg) by mouth (Po) once daily

Also known as: E7080, Lenvima

Lenvatinib; Lenvatinib plus nivolumab

Nivolumab DRUG

nivolumab 480 mg IV infusions for 30 minutes q4w

Lenvatinib plus nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shi Ming: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Guangzhou No.12 People's Hospital: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (5)

Cancer Center Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510060, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

The Third Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

Guangzhou Twelfth People 's Hospita

Guangzhou, Guangdong, 510620, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B

Interventions

lenvatinib; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ming Shi, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Proffessor

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 5, 2019
• Study Start: October 30, 2019
• Primary Completion: March 30, 2021
• Study Completion: September 30, 2022
• Last Updated: January 9, 2020

Record last verified: 2020-01

Locations

CN (5)