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

Hepatic Arterial Infusion Chemotherapy Plus Toripalimab Versus Hepatic Arterial Infusion Chemotherapy Plus Sorafenib for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: a Non-comparative, Prospective, Randomized 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 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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Toripalimab; Procedure: Hepatic arterial infusion chemotherapy; Drug: Sorafenib; Drug: systemic treatment

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Shi, MD; Phone Number: +862087343938; Email: shiming@sysucc.org.cn

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: 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.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC plus toripalimab; Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Toripalimab 240mg intravenously every 3 weeks.	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
Active Comparator: HAIC plus sorafenib; Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Sorafenib 400mg twice daily (Bid) oral dosing.	Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks; Drug: Sorafenib; 400mg bid po
Other: Patients receiving TKI plus ICI; 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.	Drug: systemic treatment; atezolizumab+bevacizumab, camrelizumab+apatinib, sintilimab+bevacizumab and so on

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: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2019
• Primary Completion (Estimated): December 20, 2023
• Study Completion (Estimated): December 20, 2023

Study Registration Dates

• First Submitted: October 20, 2019
• First Submitted That Met QC Criteria: October 20, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 12, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Sorafenib; Hepatic arterial infusion chemotherapy; Toripalimab; 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; Sorafenib
• Other Study ID Numbers: S0905 (Other Identifier: CTEP)

Drug and device information, study documents

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