TACE Plus Sorafenib Versus TACE Alone for Recurrent Intermediate Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The study is a multicenter phase III randomized trial. The purpose is to investigate both the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib versus TACE alone for recurrent intermeidate hepatocellular carcinoma patients.

Detailed Description
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The trial will recruit 162 patients with recurrent intermeidate HCC, and they will be randomized (1:1) into two groups (TACE+sorafenib group, TACE group). Patients in TACE+sorafenib group will receive TACE one day following oral sorafenib (initial dose: 400mg BID). Patients in the TACE group will receive TACE alone.

Official Title
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TRansarterial ChEmoembolization Plus SorAfenib Versus Transarterial Chemoembolization Alone for Recurrent Intermeidate Hepatocellular Carcinoma: A Phase 3, Open Label, Multicenter, Randomized Controlled Trial

Conditions
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Hepatocellular Carcinoma, Sorafenib, Transarterial Chemoembolization

Intervention / Treatment
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* Combination Product: TACE+sorafenib
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-80 years; Diagnosed as HCC based on the American Association for the Study of Liver Diseases 2018 Guideline on Liver Cancer Diagnosis; Initial tumor recurrence following curative surgical resection; there must be at least one measurable lesion via imaging. Tumor burden ≤ 50% and no distant metastasis and vascular invasion; Histologically confirmed microvascular invasion in the specimen slices of surgically removed primary tumor; Eastern Cooperative Oncology Group scoring 0-1; Child-Pugh A class; At least 3 months of life expectancy; Adequate hematologic, hepatic and renal function: absolute neutrophil count ≥ 1.5x10^9/L, platelet ≥ 75 x10^9/L, Hb ≥ 90g/L, albumin ≥ 30g/L, total bilirubin ≤ 50umol/l, ALT、AST < 5×ULN, alkaline phosphatase < 4×ULN, international normalized ratio ≤ 2.3, creatine<1.5×ULN. Exclusion Criteria: Have lesions which are diffuse or can not be evaluated via imaging. Tumor burden > 50%; Have a history of hepatic encephalopathy, refractory ascites, severe esophageal and gastric varices or variceal bleeding and obstructive jaundice; Have contraindications for TACE; Have metastasis in central nervous system; Allergic to intravenous contrast agents; Pregnant or breastfeeding women, or expecting to conceive or father children within two years; Infection of HIV, known syphilis requiring treatment; Have a known history of prior invasive malignancies within 5 years before enrolment; Patients with allotransplantation; Severe dysfunction involving heart, kidney or other organs; Severe active clinical infection which is over grade 2 based on NCI-CTC version 4; Patients with mental disorders which may impact informed consent; Unable to orally take drugs; Participating other clinical drug trials 12 months before enrolment.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transarterial chemoembolization combined with sorafenib<br>The initial dose of sorafenib is 400mg BID and the drug therapy will last till outcome events happen or the trial ends. TACE will start one day following oral sorafenib. Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (oxaliplatin 200mg, raltitrexed 4mg, epirubicin 20mg in cTACE or 70mg in dTACE) and embolizing agents (gelatin sponge or microsphere) into blood vessels that help tumor grow. | Combination Product: TACE+sorafenib<br>* The initial dose of sorafenib is 400mg BID and the drug therapy will last till outcome events happen or the trial ends. TACE will start one day following oral sorafenib. Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (oxaliplatin 200mg, raltitrexed 4mg, epirubicin 20mg in cTACE or 70mg in dTACE) and embolizing agents (gelatin sponge or microsphere) into blood vessels that help tumor grow.<br>|
| Active Comparator: Transarterial chemoembolization alone<br>Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (oxaliplatin 200mg, raltitrexed 4mg, epirubicin 20mg in cTACE or 70mg in dTACE) and embolizing agents (gelatin sponge or microsphere) into blood vessels that help tumor grow. | Procedure: TACE<br>* Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (oxaliplatin 200mg, raltitrexed 4mg, epirubicin 20mg in cTACE or 70mg in dTACE) and embolizing agents (gelatin sponge or microsphere) into blood vessels that help tumor grow.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Defined as the time from randomization until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive. | 2 years | 
| Time To Progression | Defined as the time from randomization until disease progression. | 2 years | 
| Objective Response Rate | The ratio of patients with complete response or partial response among all patients. | 2 years | 
| Disease Control Rate | The ratio of patients with complete response, partial response or stable disease among all patients. | 2 years | 
| Adverse Events | Grade 3 or severer hematological or non-hematological adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4). | 2 years | 
| Scoring of Quality of Life | Using the third edition of European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ-C30). | 2 years |