bTAE-HAIC Combined With Lenvatinib and Sintilimab for Infiltrative Hepatocellular Carcinoma

Sponsor

Sun Yat-sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06070636

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study intends to evaluate the efficacy and safety of blank- microsphere transcatheter arterial embolization-hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin (bTAE-HAIC) plus Lenvatinib and Camrelizumab for patients with infiltrative hepatocellular carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Liver Diseases Hepatocellular Carcinoma Immunotherapy Lenvatinib Sintilimab	Procedure: bTAE-HAIC Drug: Lenvatinib Drug: Sintilimab	N/A

Detailed Description

Blank-microsphere transcatheter arterial embolization (bTAE) and hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin are effective and safe for hepatocellular carcinoma. Lenvatinib is non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. Sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, is effective and safe in patients with unresectable hepatocellular carcinoma. No study has evaluated bTAE-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:

Sequential bTAE-HAIC Combined With Lenvatinib and Sintilimab for Infiltrative Hepatocellular Carcinoma

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Jan 30, 2025

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bTAE-HAIC combined with Lenvatinib and Sintilimab bTAE procedure was a 2.8-F microcatheter was super-selectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin every 4 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Sintilimab, 200 mg intravenously every 3 weeks.	Procedure: bTAE-HAIC bTAE procedure was a 2.8-F microcatheter was superselectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). The microcatheter was reserved at the proper/left/right hepatic artery according tumor location. After the patient returned to the ward, the following FOLFOX-based regime was intra-arterially administered through the microcatheter. The FOLFOX regimen was administered via the hepatic artery as follows: 85 or 135 mg/m2 oxaliplatin from hour 0 to 2 on day 1, and 400 mg/m2 leucovorin from hour 2 to 4 on day 1, and 400 mg/m2 fluorouracil bolus at hour 5 on the day 1; and 2400 mg/m2 fluorouracil over 46 h on days 1 and 2. Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Other Names: TKI inhibits Drug: Sintilimab 200mg intravenously every 32 weeks Other Names: programmed cell death protein-1 (PD-1) antibody

Arm

Intervention/Treatment

Experimental: bTAE-HAIC combined with Lenvatinib and Sintilimab

bTAE procedure was a 2.8-F microcatheter was super-selectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin every 4 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Sintilimab, 200 mg intravenously every 3 weeks.

Procedure: bTAE-HAIC

bTAE procedure was a 2.8-F microcatheter was superselectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). The microcatheter was reserved at the proper/left/right hepatic artery according tumor location. After the patient returned to the ward, the following FOLFOX-based regime was intra-arterially administered through the microcatheter. The FOLFOX regimen was administered via the hepatic artery as follows: 85 or 135 mg/m2 oxaliplatin from hour 0 to 2 on day 1, and 400 mg/m2 leucovorin from hour 2 to 4 on day 1, and 400 mg/m2 fluorouracil bolus at hour 5 on the day 1; and 2400 mg/m2 fluorouracil over 46 h on days 1 and 2.

Drug: Lenvatinib

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

Other Names:

TKI inhibits

Drug: Sintilimab

200mg intravenously every 32 weeks

Other Names:

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

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [6 months]
ORR, as determined based on tumor response according to RECIST 1.1

Secondary Outcome Measures

Progression free survival (PFS) [6 months]
PFS is defined as the time from the date of inclusion to the date of the first objectively documented tumor progression or death due to any cause.
Overall survival (OS) [12 months]
OS is the length of time from the date of inclusion until death from any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of infiltrative HCC.
Infiltrative HCC was characterized as follows: nonencapsulated arterial phase hyperenhancement; tumor washout in the period of portal phase, and noncircular, ill-defined margin
Age between 18 and 75 years;
The maximum tumor size ≥10 cm, and the total tumor size ≥15 cm;
Infiltrative HCC, with PVTT type I or type II or limited metastases (≤5).
Child-Pugh class A or B;
Eastern Cooperative Group performance status (ECOG) score of 0-2;
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
Prothrombin time ≤18s or international normalized ratio < 1.7.
Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria:

HCC with capsule;
Extrahepatic metastasis >5;
Obstructive PVTT involving the main portal vein.
Serious medical comorbidities.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510000

Sponsors and Collaborators

Sun Yat-sen University

Investigators

Study Director: Zhimei Hunag, MD, Sun Yat-sen University
Study Director: Jinhua Huang, Professor, Sun Yat-sen University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhou Qunfang, Clinical Professor, Sun Yat-sen University

ClinicalTrials.gov Identifier:

NCT06070636

Other Study ID Numbers:

Liver Project 4

First Posted:

Oct 6, 2023

Last Update Posted:

Oct 6, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Hepatocellular

Liver Diseases

Lenvatinib

Study Results

No Results Posted as of Oct 6, 2023