Systemic Chemotherapy Plus Lenvatinib and Toripalimab for HCC With Extrahepatic Metastasis

Phase 2

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: Systemic chemotherapy; Drug: Lenvatinib; Drug: Toripalimab

• Registration Number: NCT04170179
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and toripalimab in patients with hepatocellular carcinoma with extrahepatic metastasis

Detailed Description

Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for advanced hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib in overall survival in untreated 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 systemic chemotherapyplus lenvatinib and toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Study Timeline

• Study First Submitted: 2019-11-18
• Study First Submitted QC: 2019-11-18
• Study Start: 2019-11-19
• Study First Posted: 2019-11-20
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-19
• Last Update Posted: 2021-02-23
• Primary Completion: 2021-04-01
• Study Completion: 2021-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 25

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
• Presence of extrahepatic metastasis
• 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:

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

Exclusion Criteria

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• History of immunotherapy
• 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: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Systemic chemotherapy plus lenvatinib and toripalimab	Systemic chemotherapy	Systemic chemotherapy of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 240mg intravenously every 3 weeks.
Systemic chemotherapy plus lenvatinib and toripalimab	Toripalimab	Systemic chemotherapy of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 240mg intravenously every 3 weeks.
Systemic chemotherapy plus lenvatinib and toripalimab	Lenvatinib	Systemic chemotherapy of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 240mg intravenously every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Progression free survival rate at 6 months	6 months	Progression was defined as progressive disease by independent radiologic review according to mRECIST or death from any cause

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	6 months	ORR, as determined based on tumor response according to mRECIST, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.
Overall survival (OS)	6 months	OS is the length of time from the date of randomization until death from any cause.
Progression free survival (PFS)	6 months	PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause.
Adverse events	6 months	Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report.

Trial Locations

Locations (1)

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