A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.

The purpose of this study is to evaluate the safety and efficacy of doxorubicin plus sorafenib versus doxorubicin plus placebo in patients with advanced hepatocellular carcinoma (HCC).

In addition to the key secondary outcome parameters the following parameters will be assessed in an exploratory manner: relative time to progression (TTP), time to symptomatic progression (TTSP), response rate (RR) and overall survival between the 2 study populations.

The possible and potential predictive assays of clinical benefit through an assessment of the correlation between the defined baseline characteristics and key clinical endpoints.

The safety and tolerability will be assessed in the adverse event section. Doxorubicin pharmacokinetics in HCC patients treated with sorafenib versus placebo will be compared and the pharmacokinetic data will be correlated with doxorubicin-related adverse events (i.e., cardiotoxicity).

Inclusion Criteria:

• Patients who have a life expectancy of at least 12 weeks

• Patients with advanced HCC (unresectable, and/or metastatic) which has been histologically or cytologically documented

• Patients must have at least one tumor lesion that meets both of the following criteria:

  • can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST)
  • has not been previously treated with local therapy

• Patients who have received local therapy except chemoembolization, such as surgery, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a target lesion which has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of 25% in the size. Local therapy must be completed at least 4 weeks prior to the baseline scan

• Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

• Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
• History of cardiac disease
• Serious myocardial dysfunction
• Active, clinically serious infections
• Known history of Human Immunodeficiency Virus (HIV) infection
• Known Central Nervous System (CNS) tumors including metastatic brain disease
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry