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

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

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).

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.

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