Lenvatinib Plus PD-1 Antibody vs TACE for Intermediate-stage HCC Beyond Up-to-seven Criteria

Phase 3

Withdrawn

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: TACE; Drug: Lenvatinib; Drug: PD-1 antibody; Drug: TACE Drug Protocol

• Registration Number: NCT03791918
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of lenvatinib combined with PD-1 antibody compared with transarterial chemoembolization (TACE) for patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria

Detailed Description

Transarterial chemoembolization (TACE) is the most widely used palliative treatment for hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect of TACE for patients with hepatocellular carcinoma staged BCLC A/B especially for those with tumor beyond up-to-seven criteria. Recently, Lenvatinib was proved non-inferior to sorafenib in overall survival in advanced hepatocellular carcinoma, and Programmed Cell Death Protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated the efficacy and safety of lenvatinib plus PD-1 antibody in intermediate-stage HCC. Thus, the investigators carried out this prospective randomized control to demonstrate the superiority of lenvatinib combined with PD-1 antibody over TACE.

Study Timeline

• Status Verified: 2019-01
• Study Start: 2019-01-01
• Study First Submitted: 2019-01-01
• Study First Submitted QC: 2019-01-01
• Study First Posted: 2019-01-03
• Last Update Submitted: 2019-04-30
• Last Update Posted: 2019-05-02
• Primary Completion: 2022-01-01
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 B
• Beyond up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumor [in cm] and the number of tumors)
• Eastern Cooperative Oncology Group performance status of 0 to 1
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• Not applicable for transarterial chemoembolization, surgical resection, and local ablative therapy.
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lenvatinib Plus PD-1	PD-1 antibody	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.
TACE	TACE	Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA).
TACE	TACE Drug Protocol	Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA).
Lenvatinib Plus PD-1	Lenvatinib	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.

Primary Outcome Measures

Name	Time	Method
Overall survival	24 months

Secondary Outcome Measures

Name	Time	Method
Time to progression	24 months
Adverse Events	24 months
Progression free survival	24 months

Trial Locations

Locations (3)

Guangzhou Twelfth People 's Hospita; 🇨🇳 Guangzhou, Guangdong, China

Kaiping Central Hospital; 🇨🇳 Kaiping, Guangdong, China

Cancer Center Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China