Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Inclusion Criteria

• Patients must have pathologically or cytologically proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed
• Patients must have locally advanced or metastatic disease; locally advanced disease is defined as disease deemed to be unresectable or non-eligible for transplant without distant metastases
• Lesions must be accurately measurable in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan
• No prior adjuvant sorafenib or other v-RAF-1 murine leukemia viral oncogene homolog (Raf)/vascular endothelial growth factor (VEGF) inhibitors; other prior adjuvant therapy is allowed if completed > 6 months prior to registration with documented recurrence of hepatocellular carcinoma (HCC)
• Patients may have been treated with loco regional therapies provided that they either have:
• A target lesion that has not been subjected to local therapy or
• The target lesion(s) within the field of the local therapy has shown an increase of >= 20% in the size since last treatment
• Such therapy must be completed at least 4 weeks prior to registration; patients that have received palliative radiation therapy to the bone need not wait 4 weeks to begin protocol therapy
• Prior therapies allowed include the following:
• Bland embolization, radiation, radioactive microspheres, etc
• Chemoembolization using any chemotherapy (except, see below)
• Chemoembolization drug-eluting beads using doxorubicin
• Prior therapy with chemoembolization using doxorubicin in the non drug eluting beads form is NOT allowed
• No prior systemic therapy for metastatic disease
• No prior exposure to systemic doxorubicin administered intravenously
• Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior to registration
• Allografts are not allowed: no prior history of any allograft, including but not limited to liver and bone marrow transplants
• Patients must have completed any major surgery >= 4 weeks from registration
• Concomitant treatment with Rifampin or St John's wort is not allowed; patients should discontinue these drugs at least 4 weeks prior to registration
• No known central nervous system (CNS) tumors including brain metastases
• No clinically significant gastrointestinal bleeding events requiring intervention, transfusion, or admission to hospital within 30 days prior to registration
• Patients with a history of hypertension should be well controlled ( class II New York Heart Association (NYHA)
• Myocardial infarction within 6 months prior to registration
• Serious myocardial dysfunction, defined as scintigraphically (multigated acquisition scan [MUGA], myocardial scintigram) determined absolute left ventricular ejection fraction (LVEF) below 45% or an LVEF on echocardiogram (ECHO) below the normal limit at the individual institution
• No history of bleeding diathesis
• Patients receiving combination anti-retroviral therapy for human immunodeficiency virus (HIV) are excluded from the study
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Pregnancy/nursing status: women who are pregnant should not go on study; women should not breastfeed while participating in this study
• Granulocytes >= 1,500/uL
• Hemoglobin >= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure patients requiring transfusion prior to registration do not have an occult or clinically apparent gastrointestinal bleed
• Platelets >= 75,000/uL
• Creatinine = = 60 cc/minute)
• Child-Pugh score A; patients must meet all laboratory value requirements
• Bilirubin =< 3 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN
• Prothrombin time (PT)-international normalized ratio (INR) =< 1.7