FOLFOX-HAIC Plus Lenvatinib and Toripalimab vs. FOLFOX-HAIC Plus Lenvatinib for Advanced Hepatocellular Carcinoma: a Randomized Controlled and Double-blind Trial

Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Plus Lenvatinib and Toripalimab Versus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Plus Lenvatinib for Advanced Hepatocellular Carcinoma: a Phase 3, Randomized Controlled and Double-blind Trial

Our previous study showed that hepatic arterial infusion chemotherapy plus lenvatinib and toripalimab improved the survival of advanced hepatocellular carcinoma. However, Leep 002 study showded that lenvatinib plus PD-1 antibody is not superior to lenvatinib alone for advanced hepatocellular carcinoma. Thus, wo conduct this study to compare hepatic arterial infusion chemotherapy plus lenvatinib and toripalimab with hepatic arterial infusion chemotherapy plus lenvatinib for advanced hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Procedure: Hepatic arterial infusion chemotherapy; Drug: Toripalimab; Drug: oxaliplatin , fluorouracil, and leucovorin

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
      • Contact: Ming Shi, MD; Phone Number: 8620-87343115; Email: shiming@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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.
• This study did not limit HBV DNA load. High HBV-DNA load was aollowed, but hepatitis-B patient must receive concurrent antiviral therapy.
• 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

• 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: Experimental arm; Hepatic arterial infusion chemotherapy plus lenvatinib and toripalimab	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries; Drug: Toripalimab; 240 mg iv.drip Q3W; Drug: oxaliplatin , fluorouracil, and leucovorin; FOLFOX-HAIC
Active Comparator: Control arm; Hepatic arterial infusion chemotherapy plus lenvatinib	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries; Drug: oxaliplatin , fluorouracil, and leucovorin; FOLFOX-HAIC

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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03	30 days
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.	18 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.	18 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Estimated): July 26, 2025
• Study Completion (Estimated): December 26, 2026

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Hepatic arterial infusion chemotherapy; hepatocellular carcinoma; Lenvatinib; Toripalimab; Oxaliplatin, 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Protein Kinase Inhibitors; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Lenvatinib
• Other Study ID Numbers: SA23

Drug and device information, study documents

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