Lenvatinib Plus PD-1 Antibody Versus Lenvtinib Alone for Advanced HCC

Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Inhibitor Versus Lenvtinib Alone for Advanced Hepatocellular Carcinoma: a Multicentre Randomised Controlled Trial

The purpose of this study is to evaluate the efficacy and safety of lenvatinib combined with PD-1 antibody compared with lenvtinib Alone in patients with advanced hepatocellular carcinoma (HCC)

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: PD-1 antibody; Drug: Placebo

Detailed Description

Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and PD-1 antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has compared the efficacy and safety of lenvatinib plus PD-1 antibody and lenvatinib alone. Thus, the investigators carried out this prospective randomized control study to find out it.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510620
      • Guangzhou Twelfth People 's Hospita
    • Guangzhou, Guangdong, China, 510060
      • The First Affiliated Hospital of Sun Yat-Sen University
    • Kaiping, Guangdong, China, 529300
      • Kaiping Central Hospital
  • Hunan
    • Hengyang, Hunan, China, 421001
      • First Affiliated Hospital of University of South China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
• Barcelona clinic liver cancer-stage C
• Eastern Cooperative Oncology Group performance status of 0 to 2
• with no previous treatment
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
• The following laboratory parameters:
• Platelet count ≥ 75,000/μL
• Hemoglobin ≥ 8.5 g/dL
• Total bilirubin ≤ 30mmol/L
• Serum albumin ≥ 30 g/L
• ASL and AST ≤ 5 x upper limit of normal
• Serum creatinine ≤ 1.5 x upper limit of normal
• INR ≤ 1.5 or PT/APTT within normal limits
• Absolute neutrophil count (ANC) >1,500/mm3
• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Known central nervous system tumors including metastatic brain disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib Plus PD-1; Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received 3mg/kg PD-1 antibody intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Other Names: E7080, Lenvima; Drug: PD-1 antibody; 3mg/kg intravenously every 2 weeks; Other Names: Programmed cell death 1 antibody
Active Comparator: Lenvatinib alone; Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received placebo intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Other Names: E7080, Lenvima; Drug: Placebo; Intravenously every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.	12 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.	12 months
Time to Progression (TTP)	TTP was defined as the time from the date of randomization to the date of first documentation of disease progression based on mRECIST.	12 months
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03	30 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; The First Affiliated Hospital of University of South China; Guangzhou No.12 People's Hospital; Kaiping Central Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 21, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Lenvatinib; PD-1 Antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Antibodies; Immunoglobulins; Lenvatinib
• Other Study ID Numbers: HCC-renamed-S051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No