TACE Combined With Camrelizumab and Apatinib in Intermediate and Advanced Hepatocelluar Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of TACE in combination with Camrelizumab and Apatinib versus TACE in patients with intermediate- and advanced HCC.

Detailed Description
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This is a multicentric open-labal trial to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in combination with Camrelizumab and Apatinib versus TACE in patients with intermediate- and advanced hepatocellular carcinoma (HCC). The primary hypotheses is that TACE in combination with Camrelizumab and Apatinib is superior to TACE alone with respect to progression-free survival (PFS).

Official Title
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TACE Combined With Camrelizumab and Apatinib Versus TACE in Intermediate and Advanced Hepatocelluar Carcinoma: a Randomized, Open-label, Multi-center Clinical Trials

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab
* Device: TACE
* Drug: Apatinib


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 -≥18 years China liver cancer staging: Ib-IIIa Child-Pugh score ≤6 point Previous TACE treatment(≤2 times) is permitted Adequate organ and marrow function Exclusion Criteria: Participants who had another previous or current malignant tumor, except for early-stage cancer with low risk of recurrence or a malignant tumor curatively treated >5 years prior to enrolment with no recurrence Participants who have severe allergy to iodine, and unable to receive TACE Participants who have undergone a liver transplant or allogeneic bone marrow transplantation, or those who are in the waiting list for liver or bone marrow transplantation Participants who had congenital or acquired immune deficiency, such as HIV infection Participants who had a history of gastrointestinal bleeding within 6 months prior to randomization or a definite tendency of gastrointestinal bleeding Participants who had undergone arterial thromboembolism within 6 months prior to randomization or a definite tendency of gastrointestinal bleeding, such as cerebrovascular accident, ≥ CTCAE grade 3 deep vein thrombosis and pulmonary embolism

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group: TACE+Camrelizumab+Apatinib<br>Camrelizumab (iv. infusion of 200 mg); Apatinib (po. administration of 250 mg); TACE | Drug: Camrelizumab<br>* Camrelizumab: 200mg, iv, Q3W<br>Device: TACE<br>* TACE if necessary<br>Drug: Apatinib<br>* Apatinib: 250m, po, QD<br>|
| Active Comparator: Control group: TACE<br>TACE | Device: TACE<br>* TACE if necessary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) by investigator | PFS is defined as the time from randomization to progression or death from any cause. Progression in this trial was determined as untreatable (UnTACEable) progression, defined as the inability of a patients to further receive or benefit from TACE for reasons. Progression in this trial also included progression that met the JSH criteria for TACE failure/refractoriness. | Up to  2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death from any cause. | Up to  4 years | 
| PFS by investigator according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) | PFS by investigator according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) | Up to  2 years | 
| Time to untreatable (unTACEable) progression (TTUP) by investigator | TTUP is defined as the time from randomization to Child-Pugh grade C, intrahepatic tumor progression (>50% increase vs baseline), MVI or EHS (diameter>10 mm), and met the JSH criteria for TACE failure/refractoriness. | Up to  2 years |