HAIC Combined With Lenvatinib and Sintilimab for Hepatocellular Carcinoma With PVTT

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04618367

Collaborator

Second Affiliated Hospital of Guangzhou Medical University (Other)

Enrollment

Location

Arm

23.9

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study intends to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and Sintilimab for patients hepatocellular carcinoma and portal vein tumor thrombus.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular Liver Neoplasms Sintilimab Portal Vein Tumor Thrombus	Procedure: Hepatic arterial infusion chemotherapy Drug: Lenvatinib Drug: Sintilimab	N/A

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 Sintilimab, 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 Lenvatinib and Sintilimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

HAIC Combined With Lenvatinib and Sintilimab for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Anticipated Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Dec 30, 2021

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAIC plus Lenvatinib and Sintilimab Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 200 mg intravenously every 3 weeks.	Procedure: Hepatic arterial infusion chemotherapy administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 6 weeks Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Other Names: TKI inhibits Drug: Sintilimab 200mg intravenously every 3 weeks Other Names: programmed cell death protein-1 (PD-1) antibody

Arm

Intervention/Treatment

Experimental: HAIC plus Lenvatinib and Sintilimab

Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 200 mg intravenously every 3 weeks.

Procedure: Hepatic arterial infusion chemotherapy

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 6 weeks

Drug: Lenvatinib

12 mg (or 8 mg) once daily (QD) oral dosing.

Other Names:

TKI inhibits

Drug: Sintilimab

200mg intravenously every 3 weeks

Other Names:

programmed cell death protein-1 (PD-1) antibody

Outcome Measures

Primary Outcome Measures

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

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. clinical diagnosis of HCC; 2. age between18 and 75 years; 3. refused to sorafenib treatment; 4. type I PVTT, type II PVTT, or type III PVTT. 5. Child-Pugh class A or B;

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. Diffuse HCC; 2. Extrahepatic metastasis; 3. Obstructive PVTT involving both the left and right portal vein or main portal vein.

Serious medical comorbidities. 5. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy 6. Known history of HIV
History of organ allograft 8. Known or suspected allergy to the investigational agents or any agent given in association with this trial.
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.