• Overall Survival [ Time Frame: until death occurred ] [ Designated as safety issue: No ]
• Progression Free Survival [ Time Frame: until progression or death occurred ] [ Designated as safety issue: No ]
• Overall Best Tumor Response Rate [ Time Frame: achieved during treatment or within 30 days after termination of active therapy ] [ Designated as safety issue: No ]
• Time to Symptomatic Progression [ Time Frame: until first documented symptomatic progression defined by FHSI-8 assessment ] [ Designated as safety issue: No ]
• Duration of Response [ Time Frame: from first objective response to progression ] [ Designated as safety issue: No ]
• Time to Response [ Time Frame: from randomization to first objective response ] [ Designated as safety issue: No ]
• Overall Disease Control Rate (DCR) [ Time Frame: from randomization to end of treatment plus 30 days ] [ Designated as safety issue: No ]

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 TTP, TTSP, 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)

• Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
• Drug: Doxorubicin/Placebo

• Experimental: "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY 43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)
• Active Comparator: "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY 43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)

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: 1) can be accurately measured in at least one dimension according to RECIST; 2) 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 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 HIV infection
• Known CNS tumors including metastatic brain disease
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry