HAIC Plus Toripalimab vs. HAIC Plus Sorafenib for HCC With PVTT: a Non-comparative, Prospective, Randomized Trial

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: Hepatic arterial infusion chemotherapy; Drug: systemic treatment; Drug: Toripalimab; Drug: Sorafenib

• Registration Number: NCT04135690
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus toripalimab versus hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus sorafenib in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus.

Detailed Description

Our previous study showed that hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin plus sorafenib was more effective and safe than sorafenib for hepatocellular carcinoma with portal vein tumor thrombus. Programmed cell death protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has compared HAIC plus toripalimab with HAIC plus sorafenib. Thus, the investigators carried out this prospective, randomized, non-comparative study to find out it.

Study Timeline

• Study Start: 2019-10-20
• Study First Submitted: 2019-10-20
• Study First Submitted QC: 2019-10-20
• Study First Posted: 2019-10-23
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-12
• Last Update Posted: 2023-08-15
• Primary Completion: 2023-12-20
• Study Completion: 2023-12-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.
• Patients with portal vein tumor thrombus
• 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 ≥75,000/μL 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HAIC plus toripalimab	Hepatic arterial infusion chemotherapy	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Toripalimab 240mg intravenously every 3 weeks.
HAIC plus toripalimab	Toripalimab	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Toripalimab 240mg intravenously every 3 weeks.
HAIC plus sorafenib	Hepatic arterial infusion chemotherapy	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Sorafenib 400mg twice daily (Bid) oral dosing.
Patients receiving TKI plus ICI	systemic treatment	Patients, who meet the inclusion criteria but withdraw consent or reject this study, receive systemic treatment according to the doctor. Systemic treatment include atezolizumab+bevacizumab, camrelizumab+apatinib, sintilimab+bevacizumab and so on.
HAIC plus sorafenib	Sorafenib	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Sorafenib 400mg twice daily (Bid) oral dosing.

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 RECIST or death from any cause

Secondary Outcome Measures

Name	Time	Method
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.
Overall survival (OS)	6 months	OS is the length of time from the date of randomization until death from any cause.
Objective response rate (ORR)	6 months	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.
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