TACE/HAIC Combined With Lenvatinib and Sintilimab in Neoadjuvant Therapy for Intermediate-stage HCC

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05250843

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to observe the effect of TACE/HAIC combined with lenvatinib and sintilimab as a neoadjuvant therapy before liver resection in preventing the recurrence in high-risk patients with hepatocellular carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Procedure: TACE/HAIC Drug: Lenvatinib Drug: Sintilimab Procedure: liver resection	Phase 2/Phase 3

Detailed Description

For patients with hepatocellular carcinoma staged BCLC B/C(intermediate hepatocellular carcinoma)，TACE is a widely used treatments .However ,The efficacy of TACE in intermediate hepatocellular carcinoma is not very satisfactory.A series of study demonstrated that direct hepatectomy has better prognosis compared with TACE for these intermediate hepatocellular carcinoma patients.Despite of this ,The high recurrence risk, high probability of surgical complications, and poor treatment effect after recurrence of intermediate hepatocellular carcinoma after direct surgical treatment is a still a tough problem to be solved.Recently, investigators have showed that hepatic arterial infusion of FOLFOX-based chemotherapy (HAIC) was safe and efficient for advanced HCC patients. The combination of TACE with HAIC (TACE-HAIC) was proved to increase the local doses of chemotherapeutic agents in the liver .In addition, Lenvatinib was proved non-inferior to sorafenib in overall survival in advanced hepatocellular carcinoma, and Programmed Cell Death Protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma.In this context，for those patients with potentially high recurrence risk after liver resection, the investigators carried out this prospective randomized control to demonstrate the superiority of TACE/HAIC combined with PD-1 antibody and lenvatinib as a neoadjuvant therapy before liver resection over direct hepatectomy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

TACE/HAIC Combined With Lenvatinib and Sintilimab in Neoadjuvant Therapy for Patients With Potentially High Recurrence Risk After Liver Cancer Resection: a Prospective, Randomized, Controlled Clinical Study

Anticipated Study Start Date :

Apr 30, 2022

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TACE/HAIC and Lenvatinib and PD-1(Sintilimab) before liver resection For patients staged BCLC B/C,TACE/HAIC combined with Lenvatinib and Sintilimab will be conducted as neoadiuvent therapy before liver resection	Procedure: TACE/HAIC Within 1-3 days of lenvatinib and sintilimab, start Transarterial chemobolization treatment or FOLFOX-based chemotherapy infusion,after three months,patients who achieved partial response (PR) or minor response (MR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and were assessed as eligible for R0 resection go on to undergo surgical resection. Drug: Lenvatinib Participants received lenvatinib capsules 8mg for patients weight <60kg, or 12mg for patients weight more than 60Kg. Drug: Sintilimab Sintilimab Injection will be administered every three weeks (200mg) until surgery or disease progression.
Active Comparator: Direct surgery group After being diagnosed with hepatocellular carcinoma, surgery will be immediately performed.	Procedure: liver resection liver resection is feasible after evaluation by the liver cancer surgery expert group

Arm

Intervention/Treatment

Experimental: TACE/HAIC and Lenvatinib and PD-1(Sintilimab) before liver resection

For patients staged BCLC B/C,TACE/HAIC combined with Lenvatinib and Sintilimab will be conducted as neoadiuvent therapy before liver resection

Procedure: TACE/HAIC

Within 1-3 days of lenvatinib and sintilimab, start Transarterial chemobolization treatment or FOLFOX-based chemotherapy infusion,after three months,patients who achieved partial response (PR) or minor response (MR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and were assessed as eligible for R0 resection go on to undergo surgical resection.

Drug: Lenvatinib

Participants received lenvatinib capsules 8mg for patients weight <60kg, or 12mg for patients weight more than 60Kg.

Drug: Sintilimab

Sintilimab Injection will be administered every three weeks (200mg) until surgery or disease progression.

Active Comparator: Direct surgery group

After being diagnosed with hepatocellular carcinoma, surgery will be immediately performed.

Procedure: liver resection

liver resection is feasible after evaluation by the liver cancer surgery expert group

Outcome Measures

Primary Outcome Measures

Recurrence-free Survival [12 months]
Time from the start of liver resection until tumor recurrence or death (from any cause).

Secondary Outcome Measures

Adverse effects [12 months]
Frequency and severity of adverse effects as defined by CTCAE version 5

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Age 18-70 years old, gender is not limited.
2)The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL).
3)Patients must have at least one tumor lesion that can be accurately measured.
4)Conform to any of the following criteria (1) multiple nodules >3; (2) ≥2 nodules, any of which is >3 cm; (3) invasion of the portal vein or hepatic vein.
5)According to the 2022 edition of the Chinese guidelines for the diagnosis and treatment of primary liver cancer, one-stage liver cancer resection is feasible after evaluation by the liver cancer surgery expert group
6)No previous anti-HCC treatment.
7)Eastern Co-operative Group performance status 2 or less.
8)Liver function: Child's A or B (score < 7).

Exclusion Criteria:

1)Patients with definite tumor thrombus and distant metastasis in the main portal vein and inferior vena cava;
1. Allergy to the components of intervention-related drugs such as lipiodol and chemotherapeutic drugs;
1. Local treatment (including intervention, surgery, ablation, etc.) and systemic treatment (chemotherapy, targeted drugs and immune checkpoint inhibitors, etc.) for liver cancer within the past 2 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510630

Sponsors and Collaborators

Third Affiliated Hospital, Sun Yat-Sen University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhang Yingcai, doctorate, Third Affiliated Hospital, Sun Yat-Sen University

ClinicalTrials.gov Identifier:

NCT05250843

Other Study ID Numbers:

LHuanxian

First Posted:

Feb 22, 2022

Last Update Posted:

Feb 22, 2022

Last Verified:

Feb 1, 2022

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:

Keywords provided by Zhang Yingcai, doctorate, Third Affiliated Hospital, Sun Yat-Sen University

Lenvatinib

TACE

PD-1

Additional relevant MeSH terms:

Carcinoma, Hepatocellular

Lenvatinib

Study Results

No Results Posted as of Feb 22, 2022