TACE Combinated With Sorafenib in Treating Patients With Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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TACE is widely used in patients with unresectable HCC. However, it is a non-curative approach; thus ,strategies to further improve the survival of these patients are needed. Sorafenib is regarded as standard treatment for advanced HCC. It is the first systemic therapy to demonstrate a significant survival benefit in HCC patients.The hypothesis is that the combination of TACE with sorafenib could improve the survival of patients with unresectable HCC.

Official Title
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Phase II Trail of TACE Combinated With Sorafenib in Treating Patients With Unresectable Hepatocellular Carcinoma

Conditions
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PHENYTOIN/SORAFENIB [VA Drug Interaction], Carcinoma, Hepatocellular

Intervention / Treatment
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* Procedure: TACE
* Drug: sorafenib combined with TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients newly diagnosed as HCC according to European Association for Study of the Liver criteria. BCLC stage B or C Child-Pugh class score≤8 ECOG performance status ≤2 Etiology: Hepatitis B virus(HBV) infection Written informed consent (approved by the Institutional Review Board [IRB]obtained prior to any study specific screening procedures Patient must be able to comply with the protocol Age 18-75 years Haematology:Absolute neutrophil count (ANC) > 1.5 x 109/L, Platelet count > 50 x 109/L, Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time international normalized ratio < 1.5 Biochemistry:Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)< 5 x the upper limit of normal,Total bilirubin < 3 x the upper limit of normal,Serum creatinine < 1.5 x the upper limit of normal,Cholinesterase>0.5x the lower limit of normal，Prealbumin>0.5x the lower limit of normal. Life expectancy of > 3 months Exclusion Criteria: BCLC stage D Child-Pugh Score≥9 Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment Preexisting or history of hepatic encephalopathy uncontrolled hypertension Pregnancy (positive serum pregnancy test) or lactation Serious, non-healing wound, ulcer, or bone fracture Currently or recent (within the 30 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents ( ≤ 6 months prior to study entry), myocardial infarction ( ≤ 6 months prior to study entry), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Sorafenib/TACE or patient at high risk from treatment complications Other severe concomitant disease that may reduce life expectancy Risk of allergic reactions to the study drugs Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group TACE<br>TACE will be carried out with chemotherapeutic agents and lipiodol; additional embolisation will be carried out with gelatin sponge particles. TACE will be repeated if clinically indicated | Procedure: TACE<br>* After obtaining arterial access,a diagnostic visceral arteriogram will be performed to demonstrate arterial supply to the tumor and the presence of variant arterial anatomy.After having positioned the catheter within the artery feeding tumor,the chemoembolization mixture will be infused into th e artery until stagnant flow is observed.<br>|
| Experimental: Group Combination<br>All patients will receive Sorafenib (800 mg/day) p.o. beginning four weeks after the first TACE and every day thereafter until patient death or premature withdrawal from study | Drug: sorafenib combined with TACE<br>* All patients will receive Sorafenib (800 mg/day) p.o. beginning four weeks after the first TACE and every day thereafter until patient death or premature withdrawal from study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression is defined as time from randomization to radiological progression and will be evaluated every 8 week | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FACT-Hep | FACT-Hep is a chart established to evaluate the life quality of patients with HCC every 4 weeks | six months | 
| Disease control rate | CR+PR+SD | six months after TACE | 
| Safety | Number of participants with adverse events as a measure of safety and tolerability(According to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) | six months | 
| PFS and OS | The overall survival is defined as time from randomization to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period,respectively | two years | 
| Number of TACE sessions and the interval time between two TACE sessions |  | 2 years | 
| AFP |  | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, transarterial chemoembolization, sorafenib