Sorafenib VS TACE in HCC Patients With Portal Vein Invasion

Study Overview
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Brief Summary
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The investigators are going to compare the therapeutic effect of sorafenib and transarterial chemoembolization in advanced hepatocellular carcinoma with major branch of portal vein invasion.

Detailed Description
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TACE is an established therapy for patients with unresectable hepatocellular carcinoma (HCC) and has been shown to significantly improve survival in these patients compared to no treatment. Moreover, TACE can be performed safely and may improve the overall survival of patients with HCC and major branch of portal vein invasion. Sorafenib, already approved for HCC, could lead to significantly improvement in tumor control and survival in patients with advanced stage HCC. So far there are no head to head comparison reports about the efficacy of Sorafenib and TACE. Here the investigators evaluate the efficacy of sorafenib and TACE in advanced HCC with major branch of portal vein invasion.

Official Title
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An Open Label, Phase 2 Trial Comparing Sorafenib And TACE in Advanced Hepatocellular Carcinoma With Portal Vein Invasion

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sorafenib
* Procedure: TACE for HCC with portal vein invasion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 80 > Age >= 18 years. Child-Pugh class A (class B could be included when Childs score is 7). Hepatocellular carcinoma with major branch of portal vein invasion on dynamic CT or MRI not only newly diagnosed treatment-naive patients, but also HCC patients previously treated with other therapies in case of development of major branch of portal vein invasion Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell counts (WBC) >= 2,000 /μl, Absolute neutrophil count (ANC) > 1,200/μl Hemoglobin >= 8.0 g/dl Platelet count > 50,000/μl Serum creatinine < 1.7 mg/dl Total bilirubin =< 3.0 mg/dl Prothrombin Time (PT)-international normalized ratio (INR) =< 2.3 or Prothrombin Time (PT)-sec =< 6 sec Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Exclusion Criteria: Child-Pugh score >= 8. Age < 18 or >= 80 years. ECOG Performance Status >= 3. Recipient of living donor or deceased donor liver transplantation Patients unable to understand the contents of informed consent or refuse to sign the informed consent. Patients with evidence of uncontrolled or severe medical conditions requiring treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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 |
| --- | --- |
| Active Comparator: Sorafenib<br>Sorafenib 400mg po bid | Drug: Sorafenib<br>* Sorafenib 400mg po bid<br>* Other names: Nexavar;|
| Experimental: TACE for HCC with portal vein invasion<br>Antineoplastic agents are directly injected into the hepatic artery, allowing high intratumoral concentrations of drugs and thereby reducing systemic side effects. The mixture of chemotherapeutic agents and iodized oil is almost completely retained in neoplastic nodules and can remain in HCC tissue for a long time. Subsequent mechanical embolization of the artery feeding the neoplasm causes ischemic damage to the tumor and prolongs the duration of the effects of chemotherapeutic agents. | Procedure: TACE for HCC with portal vein invasion<br>* The volume of iodized oil ranged from 2 to 12 mL, and the amount of doxorubicin ranged from 10 to 60 mg. Gelatin sponge particles were mixed with mitomycin and contrast material.Cisplatin was infused at the tumor feeder vessels as a solution with a concentration of 0.5 mg/mL at a rate of 5-10 mL/min. The total amount of cisplatin used ranged from 50 to 100 mg depending on the patient's body weight and the level of infusion.<br>* Other names: TACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (Efficacy) |  | every 6 weeks up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | every 6 weeks up to 3 years | 
| objective tumor response rate | Determined by dynamic-perfusion CT scan at the end of each cycle | every 6 weeks up to 3 years | 
| objective tumor control rate | Determined by dynamic-perfusion CT scan at the end of each cycle | every 6 weeks up to 3 years | 
| progression-free survival |  | every 6 weeks up to 3 years | 
| the adverse event rate and examine the toxicities | The investigators will evaluate the adverse event according to Common Toxicity Criteria(version 4.0)by National Cancer Institute of National Institutes of Health | every 6 weeks up to 3 years | 
| Change of perfusion parameter |  | every 6 weeks up to 3 years | 
| Alpha feto protein (AFP) responsiveness | AFP responder : 20% reduction from baseline AFP level after 6 weeks of treatment | every 6 weeks up to 3 years |