Sorafenib in First-line Treatment of Advanced B Child Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to to compare the addition of sorafenib (800 mg/day)to best supportive care with best supportive care alone in terms of survival in patients with hepatocellular carcinoma (HCC) with impaired liver function (Child B).

Detailed Description
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Hepatocellular carcinoma (HCC) is the third cause of death for cancer in the world with an increasing incidence. No systemic therapy has proven effective in patients with advanced HCC until 2007, when results of the SHARP trial were presented. In this trial, the orally active multi-kinase inhibitor sorafenib (800 mg/day) significantly prolonged survival compared with placebo in patients with advanced HCC and good liver function (Child A). The same authors concluded that the effect of the drug in the population of patients with more impaired liver function should be further studied.

Official Title
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Sorafenib in the First Line Treatment of Advanced Hepatocellular Carcinoma With Child-Pugh Liver Function Class B: Multicentre Phase 3 Randomized Trial

Conditions
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Advanced Adult Hepatocellular Carcinoma

Intervention / Treatment
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* Other: Best Supportive Care
* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diagnosis of hepatic cell carcinoma (HCC) according to the AASLD- EASL criteria Age >18 years Advanced stage of disease defined as HCC not eligible for locoregional treatments (ab initio or following progression after such treatments) Liver function classified as Child-Pugh class B ECOG performance status < or = 2 Life expectancy of at least 2 months Adequate contraception for fertile male and female patients Signed informed consent Exclusion Criteria: Prior exposure to sorafenib or antiangiogenesis drugs Concomitant diseases that contraindicate the use of sorafenib Gastro-intestinal bleeding in the previous 30 days Altered renal function(creatinine > 1.5 x ULN), or haematological function (platelet count < 60 x 10^9/L, hemoglobin < 9 g/dl) Serious active infections (> grade 2 CTCAE version 3.0) Congestive heart failure, history of congestive heart failure, unstable angina pectoris, myocardial infarct or significant valvular heart disease or uncontrolled heart arrhythmia Patients who are unable or unwilling to participate in the study Pregnant or lactating females Hepatic encephalopathy of any grade

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 |
| --- | --- |
| Active Comparator: A: Best Supportive Care<br>best supportive care | Other: Best Supportive Care<br>* Therapy given according to clinical practices at participating centres. Experimental therapies not permitted.<br>|
| Experimental: B: Sorafenib 400 mg, twice a day + Best Supportive Care<br>sorafenib + best supportive care | Other: Best Supportive Care<br>* Therapy given according to clinical practices at participating centres. Experimental therapies not permitted.<br>Drug: sorafenib<br>* 400 mg twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| worst grade toxicity per patient | worst grade toxicity (according to Common Terminology Criteria for Adverse Events version 4.03) per patient in both treatment arms | every 4 weeks | 
| quality of life |  | every 4 weeks for 6 months | 
| progression free survival |  | every 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Child Pugh B, first line