TACE in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies for Intermediate HCC

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: TACE; Drug: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab

• Registration Number: NCT05332496
• Lead Sponsor: Zhongda Hospital

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with PD-1/PD-L1 Inhibitors and molecular target therapies in patients with Intermediate-stage hepatocellular carcinoma (HCC).

Detailed Description

Transarterial chemoembolization (TACE) can induce immunogenic cell death and tumor-specific immune response which results in the release of tumor antigens and transform "cold" tumors with lacking immune effector cells into "hot" tumors with immune effector cells infiltration. This provides a theoretical basis for TACE combined with immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients. The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with PD-1/PD-L1 Inhibitors and molecular target therapies(including, VEGF-TKI/ bevacizumab) in patients with Intermediate-stage HCC. This real-world study also would like to explore the optimal combined treatment and subgroup of HCC patients for providing further information for clinical practice and trials.

Study Timeline

• Study First Submitted: 2022-04-02
• Study First Submitted QC: 2022-04-10
• Study First Posted: 2022-04-18
• Status Verified: 2022-12
• Study Start: 2022-12-28
• Last Update Submitted: 2022-12-28
• Last Update Posted: 2022-12-29
• Primary Completion: 2023-08-31
• Study Completion: 2023-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
2. Barcelona Clinic Liver Cancer (BCLC) stage B, without the presence of extrahepatic spread and/or macrovascular invasion;
3. Has not received any previous TACE/HAIC and systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy);
4. Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval;
5. TACE was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment;
6. Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after TACE treatment；
7. Has repeated measurable intrahepatic lesions according to mRECIST;

Exclusion Criteria

1. Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible;
2. Unable to meet criteria of combination timeframe described above;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control group: TACE	TACE	TACE monotherapy
Study group: TACE+PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab	TACE	TACE was performed up to 3 months after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or within 1 month before treatment. The interval between first use PD-1/PD-L1 inhibitors and anti-angiogenesis drugs ≤1 week；
Study group: TACE+PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab	PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab	TACE was performed up to 3 months after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or within 1 month before treatment. The interval between first use PD-1/PD-L1 inhibitors and anti-angiogenesis drugs ≤1 week；

Primary Outcome Measures

Name	Time	Method
Progression free survival(PFS) per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	up to approximately 2 years	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to mRECIST) or death due to any cause, whichever occurs first.
Overall Survival(OS)	up to approximately 2 years	The OS is defined as the time from the initiation of any combination treatment to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
DCR per RESCIST 1.1	up to approximately 2 years	DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD)per RESCIST 1.1.
Disease Control Rate (DCR) per mRECIST	up to approximately 2 years	DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per mRECIST.
PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	up to approximately 2 years	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to RECIST 1.1) or death due to any cause, whichever occurs first.
Objective response rate(ORR) per mRECIST	up to approximately 2 years	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per mRECIST.
DOR per RESCIST 1.1	up to approximately 2 years	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR until the first documented disease progression (according to RESCIST 1.1) or death due to any cause, whichever occurs first.
ORR per RESCIST 1.1	up to approximately 2 years	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0	up to approximately 2 years	The percentage and degree of patients who experience at least one AE, whether or not considered related to the treatment, according to CTCAE version 5.0.
Duration of Response (DOR) per mRECIST	up to approximately 2 years	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR until the first documented disease progression (according to mRECIST) or death due to any cause, whichever occurs first.

Trial Locations

Locations (2)

Zheng-Gang Ren; 🇨🇳 Nanjing, China

Gao-Jun Teng; 🇨🇳 Nanjing, China