HAIC Combined With Bevacizumab and Toripalimab for Advanced Hepatocellular Carcinama

Phase 2

• Conditions: Toripalimab; Hepatocellular Carcinoma; Oxaliplatin; Bevacizumab; Liver Neoplasms
• Interventions: Procedure: Hepatic arterial infusion chemotherapy; Drug: Bevacizumab; Drug: Toripalimab

• Registration Number: NCT04627363
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This is an open-label, single-arm clinical study to preliminarily observe and evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin synchronous combined with Bevacizumab and Toripalimab as the first-line therapy for advanced HCC.

Detailed Description

Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for hepatocellular carcinoma. Bevacizumab, an angiogenesis Inhibitors was effectively used for hepatocelluar carcinama (HCC) therapy. Toripalimab, an programmed cell death protein-1 (PD-1) antibody, was effective and tolerable in patients with hepatocellular carcinoma and portal vein tumor thrombus. No study has evaluated HAIC plus Bevacizumab and Toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Study Timeline

• Status Verified: 2020-11
• Study First Submitted: 2020-11-12
• Study First Submitted QC: 2020-11-12
• Last Update Submitted: 2020-11-12
• Study First Posted: 2020-11-13
• Last Update Posted: 2020-11-13
• Study Start: 2021-01-01
• Primary Completion: 2022-06-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. HCC diagnosed by histopathological examination or Guidelines for Diagnosis and Treatment of Primary Liver Cancer or the recurrent HCC after surgery;
2. age between 18 and 75 years;
3. Stage B (middle stage) or C (late stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage). In case of stage B.
4. No previous use of any systemic therapy or recurrent HCC.
5. Child-Pugh class A or B;
6. Eastern Cooperative Group performance status (ECOG) score of 0-2;
7. 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
8. Prothrombin time ≤18s or international normalized ratio < 1.7.
9. Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria

1. Cholangiocellular carcinoma (ICC);
2. Patients with cancer thrombus in the main trunk of portal vein (Vp4), or cancer thrombus in inferior vena cava should be excluded;
3. Accepting ablation or surgery or other system therapy as firt line therapy after diagnose for primary HCC, ablation or system therapy as first line therapy for recurrent HCC.
4. Serious medical comorbidities.
5. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
6. Known history of HIV
7. History of organ allograft
8. Known or suspected allergy to the investigational agents or any agent given in association with this trial.
9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
10. Evidence of bleeding diathesis.
11. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HAIC plus Bevacizumab and Toripalimab	Hepatic arterial infusion chemotherapy	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab, 240 mg intravenously every 3 weeks. Bevacizumab 15 mg/kg intravenously every 3 weeks.
HAIC plus Bevacizumab and Toripalimab	Bevacizumab	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab, 240 mg intravenously every 3 weeks. Bevacizumab 15 mg/kg intravenously every 3 weeks.
HAIC plus Bevacizumab and Toripalimab	Toripalimab	Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab, 240 mg intravenously every 3 weeks. Bevacizumab 15 mg/kg 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 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.
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.