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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Intermediate Stage HCC

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of HCC confirmed by radiology, histology, or cytology; Barcelona Clinic Liver Cancer (BCLC) stage B, without the presence of extrahepatic spread and/or macrovascular invasion; Has not received any previous TACE/HAIC and systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy); Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval; TACE was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment; Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after TACE treatment； Has repeated measurable intrahepatic lesions according to mRECIST; Exclusion Criteria: Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible; Unable to meet criteria of combination timeframe described above;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group: TACE+PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab<br>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； | Drug: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab<br>* PD-1/PD-L1 inhibitors: atezolizumab, sintilimab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, toripalimab, durvalumab, penpulimab, and other ICIs; VEGF-TKI/bevacizumab: sorafenib, lenvatinib, donafenib, apatinib, anlotinib, bevacizumab/ bevacizumab biosimilar, and other anti-angiogenesis drugs; Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs only include marketed drugs but are not limited to HCC approval.<br>Procedure: TACE<br>* TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE);<br>|
| Control group: TACE<br>TACE monotherapy | Procedure: TACE<br>* TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE);<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 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. | up to approximately 2 years | 
| Overall Survival(OS) | The OS is defined as the time from the initiation of any combination treatment to death due to any cause. | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 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. | up to approximately 2 years | 
| Objective response rate(ORR) per mRECIST | The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per mRECIST. | up to approximately 2 years | 
| Duration of Response (DOR) per mRECIST | 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. | up to approximately 2 years | 
| Disease Control Rate (DCR) per mRECIST | DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per mRECIST. | up to approximately 2 years | 
| ORR per RESCIST 1.1 | The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1. | up to approximately 2 years | 
| DOR per RESCIST 1.1 | 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. | up to approximately 2 years | 
| DCR per RESCIST 1.1 | 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. | up to approximately 2 years | 
| Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0 | 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. | up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, transarterial chemoembolization, immune checkpoint inhibitors, molecular target therapies, Intermediate stage