HAIC Plus Lenvatinib and Toripalimab for Advanced HCC

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Toripalimab for Advanced Hepatocellular Carcinoma： a Prospective, Single-arm Trial

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and toripalimab in patients with advanced hepatocellular carcinoma (HCC)

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: Toripalimab; Procedure: Hepatic arterial infusion chemotherapy

Detailed Description

Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for 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 HAIC plus lenvatinib and toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

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

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:

Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC plus Lenvatinib and Toripalimab; Hepatic arterial infusion 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.	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Drug: Toripalimab; 240mg intravenously every 3 weeks; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival rate at 6 months	Progression was defined as progressive disease by independent radiologic review according to RECIST or death from any cause	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is the length of time from the date of randomization until death from any cause.	6 months
Progression free survival (PFS)	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.	6 months
Adverse events	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.	6 months
Objective response rate (ORR)	ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.	6 months

Collaborators and Investigators

• Sponsor: Shi Ming

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: August 1, 2019
• First Submitted That Met QC Criteria: August 1, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Lenvatinib; Toripalimab; Hepatic artery infusion chemotherapy; Oxaliplatin, 5-Fluorouracil and Leucovorin
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: HCC-S0903

Drug and device information, study documents

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