TACE Combined With Penpulimab and Anlotinib for Advanced HCC

Study Overview
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Brief Summary
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The purpose of this multicenter, dual-cohort, prospective real-world study is to explore the efficacy and safety of penpulimab and anlotinib combined with or without TACE, as well as the optimum interval of the combination of penpulimab and anlotinib with TACE in advanced HCC patients.

Detailed Description
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The efficacy and safety of transarterial chemoembolization (TACE) combined with penpulimab and anlotinib in the treatment of advanced hepatocellular carcinoma (HCC) remain unknown. This is a multicenter, dual-cohort, prospective real-world study with patients receiving normal clinical care. Patients in cohort I will receive TACE combined with penpulimab and anlotinib (TACE-A-A Cohort), and patients in cohort II will just receive penpulimab and anlotinib (A-A Cohort). The primary endpoints of this study are the efficacy of penpulimab and anlotinib combined with or without TACE in advanced HCC patients. While the secondary endpoints include the safety of penpulimab and anlotinib combined with or without TACE, as well as the optimum interval of the combination of penpulimab and anlotinib with TACE in advanced HCC patients. The results will provide further evidence for the clinical practice and the design of future trials.

Official Title
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Transarterial Chemoembolization Combined With Penpulimab and Anlotinib for Advanced Hepatocellular Carcinoma：A Nationwide Multicenter Prospective Real-world Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: TACE+penpulimab+anlotinib vs. penpulimab+anlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Pathologically or clinically diagnosed HCC patients; Age of 18-80; Barcelona Clinic Liver Cancer (BCLC) stage C (ie, China Liver Cancer Staging (CNLC) stage III); with expect survival ≥ 3 months; with obtained informed consent; will receive penpulimab and anlotinib combined with or without TACE. Exclusion criteria: Contraindications of penpulimab and anlotinib; Child-Pugh C; Key information (such as imaging, liver function, Eastern Cooperative Oncology Group(ECOG) score, etc.) missing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients in cohort I will receive TACE combined with penpulimab and anlotinib (TACE-A-A Cohort), and patients in cohort II will just receive penpulimab and anlotinib (A-A Cohort).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I（TACE-A-A Cohort）<br>Patients will receive TACE as needed; penpulimab 200 mg i.v. every 3 weeks(Q3W); and anlotinib 12 mg orally before breakfast,everyday(QD); continue taking for 2 weeks and stop for 1 week, that is, 3 weeks (21 days) as a course of treatment. | Drug: TACE+penpulimab+anlotinib vs. penpulimab+anlotinib<br>* Patients will receive TACE as needed; penpulimab 200 mg i.v. every 3 weeks(Q3W); and anlotinib 12 mg orally before breakfast,everyday(QD); continue taking for 2 weeks and stop for 1 week, that is, 3 weeks (21 days) as a course of treatment.<br>* Other names: The combination of penpulimab+anlotinib with or without TACE;|
| Experimental: Cohort II (A-A Cohort)<br>Patients will receive penpulimab 200 mg i.v. every 3 weeks(Q3W); and anlotinib 12 mg orally before breakfast,everyday(QD); continue taking for 2 weeks and stop for 1 week, that is, 3 weeks (21 days) as a course of treatment. | Drug: TACE+penpulimab+anlotinib vs. penpulimab+anlotinib<br>* Patients will receive TACE as needed; penpulimab 200 mg i.v. every 3 weeks(Q3W); and anlotinib 12 mg orally before breakfast,everyday(QD); continue taking for 2 weeks and stop for 1 week, that is, 3 weeks (21 days) as a course of treatment.<br>* Other names: The combination of penpulimab+anlotinib with or without TACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Time from initiation of either combination therapy to tumor progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria or death from any cause. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate(ORR) | The proportion of patients with complete response (CR) and partial response (PR) according to the mRECIST criteria. | 2 years | 
| Overall survival (OS) | The time from initiation of either regimen of combination therapy to all-cause death. | up to 5 years | 
| Adverse effects | Adverse event (AE)，treatment emergent adverse event(TEAE)，serious adverse event (SAE) | 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, Penpulimab, Anlotinib