A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

• Time to Progression (TTP) [ Time Frame: from date of randomization of the first patient until 3 years later ] [ Designated as safety issue: No ]
  TTP was defined as the time from randomization to radiological disease progression by independent assessment.
  
  

• Overall Survival [ Time Frame: from date of randomization of the first patient until 3 years later ] [ Designated as safety issue: No ]
  The time from date of randomization to date of death
  
  
• Progression Free Survival (PFS) [ Time Frame: from date of randomization of the first patient until 3 years later ] [ Designated as safety issue: No ]
  Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first
  
  
• Percentage of Participants in Each Category of Best Tumor Response [ Time Frame: achieved during treatment or within 30 days after termination of active therapy ] [ Designated as safety issue: No ]
  Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
  
  
• Time to Symptomatic Progression (TTSP) [ Time Frame: from date of randomization of the first patient until 3 years later ] [ Designated as safety issue: No ]
  Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment
  
  
• Duration of Response [ Time Frame: from date of randomization of the first patient until 3 years later ] [ Designated as safety issue: No ]
  Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first
  
  
• Time to Response (TTR) [ Time Frame: from date of randomization until 3 years later at end of study ] [ Designated as safety issue: No ]
  Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria
  
  
• Percentage of Participants for Whom Disease Control Was Achieved [ Time Frame: from date of randomization to end of treatment plus 30 days ] [ Designated as safety issue: No ]
  Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST)
  
  

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).