Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Transarterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). However, the hypoxia caused by TACE in surviving tumor cell leads to release of angiogenic and growth factors contributing to poor outcome. Sorafenib can block tumor cell proliferation and angiogenesis. The hypothesis is that patients with unresectable HCC may benefit from sorafenib in combination with TACE.

Official Title
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Phase II Trail of Sorafenib Combined With Transarterial Chemoembolization in HBV-infected Patients With Intermediate Hepatocellular Carcinoma

Conditions
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PHENYTOIN/SORAFENIB [VA Drug Interaction], Liver Neoplasms, Carcinoma, Hepatocellular, Digestive System Neoplasms, Neoplasms by Site, Liver Diseases, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, DOXORUBICIN/TRASTUZUMAB [VA Drug Interaction], HBV

Intervention / Treatment
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* Procedure: Transarterial Chemoembolization (TACE)
* Other: Sorafenib in combination 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 Child-Pugh class A ECOG performance status of 0 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 18-80 years Haematology:Absolute neutrophil count (ANC) > 1 x 109/L, Platelet count > 40 x 109/L, Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time international normalized ratio < 1.5 Biochemistry:Total bilirubin < 2 mg/dL Serum creatinine < 1.5 x the upper limit of normal Life expectancy of > 3 months Exclusion Criteria: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 x the upper limit of normal Other severe concomitant disease that may reduce life expectancy uncontrolled hypertension Pregnancy (positive serum pregnancy test) or lactation Uncontrolled hypertension 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

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group TACE<br>Patients who undergo TACE | Procedure: Transarterial Chemoembolization (TACE)<br>* Procedure:TACE TACE will be carried out with an emulsion of 50mg doxorubicin with lipiodol in a total volume of 10-20 mL; additional embolisation will be carried out with gelatin sponge particles. TACE will be repeated every 4 weeks for 2 cycles; additional cycles will be offered if clinically indicated .<br>|
| Experimental: Group Combination<br>Patients who are treated with sorafenib combined with TACE | Other: Sorafenib in combination with TACE<br>* Drug: Sorafenib All patients will receive Sorafenib (800 mg/day) p.o. beginning one week after the first TACE and every day thereafter until patient death or premature withdrawal from study. Procedure: TACE TACE will be carried out with an emulsion of 50mg doxorubicin with lipiodol in a total volume of 10-20 mL; additional embolisation will be carried out with gelatin sponge particles. TACE will be repeated every 4 weeks for 2 cycles; additional cycles will be offered if clinically indicated .<br>* Other names: Sorafenib:Nexavar(brand name);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of sorafenib in increasing the effectiveness of transarterial chemoembolization (TACE) | Measure:time-to-proression | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of sorafenib in combination with TACE | Measure: incidence and grade of adverse events in patients treated with sorafenib combined with TACE (group B) | 6 months | 
| Survival in the two treatment groups | Measured from the date of TACE until the date of death or last visit | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Sorafenib, Transarterial Chemoembolization, HBV