Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)

• Time to Progression, response rate, duration of response, disease control rate determined by tumor measurement using Magnetic Resonance Imaging (MRI) or CT scans [ Time Frame: Every 6 weeks during treatment ] [ Designated as safety issue: No ]
• Health Related Quality of Life and Utility Values as measured by the EQ-5D [ Time Frame: Every 6 weeks during treatment ] [ Designated as safety issue: No ]
• Laboratory testing [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]
• Adverse Event collection [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]
• Electrocardiogram [ Time Frame: At the start and at the completion of treatment ] [ Designated as safety issue: Yes ]
• Vital signs [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]

• Time to Progression, response rate, duration of response, disease control rate determined by tumor measurement using MRI or CT scans [ Time Frame: Every 6 weeks during treatment ] [ Designated as safety issue: No ]
• Health Related Quality of Life and Utility Values as measured by the EQ-5D [ Time Frame: Every 6 weeks during treatment ] [ Designated as safety issue: No ]
• Laboratory testing [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]
• AE reporting [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]
• ECG [ Time Frame: At the start and at the completion of treatment ] [ Designated as safety issue: Yes ]
• Vital signs [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: Yes ]

This is a randomized trial to evaluate the clinical benefit of sorafenib 400 mg twice daily and erlotinib 150 mg once a day versus sorafenib 400 mg twice daily and placebo erlotinib once daily in subjects with unresectable advanced or metastatic Child-Pugh A HCC. Patients who are candidates for potentially curative intervention (i.e. surgical resection or local ablation) are not eligible for this study.

• Drug: Sorafenib (Nexavar, BAY43-9006)
  Sorafenib 400 mg twice daily + Matching Erlotinib Placebo daily
• Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva
  Sorafenib 400 mg twice daily + Erlotinib 150 mg daily

• Experimental: Arm 1
  Intervention: Drug: Sorafenib (Nexavar, BAY43-9006)
• Active Comparator: Arm 2
  Intervention: Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva

Inclusion Criteria:

• Patients > 18 years of age
• Patients who have a life expectancy of at least 12 weeks
• Patients with histological or cytologically documented HCC

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

  • The lesion can be accurately measured in at least one dimension according to RECIST
  • The lesion has not been previously treated with local therapy
• Patients who have an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
• Cirrhotic status of Child-Pugh class A.
• Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time.

Exclusion Criteria:

• History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted.
• Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sogren's syndrome) including congenital abnormality (e.g. Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g. fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test).
• History of interstitial lung disease (ILD).
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Previous treatment with yttrium-90 spheres
• Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
• Uncontrolled ascites (defined as not easily controlled with diuretic treatment)