Sorafenib Tosylate Before and After Hepatic Arterial Chemoembolization With Doxorubicin Hydrochloride and Mitomycin C in Treating Patients With Localized Liver Cancer That Cannot Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular carcinoma (HCC)

  • Single lesion > 6.5 cm; > 3 tumors, any tumor with a diameter > 4.5 cm; or a cumulative tumor diameter > 8.0 cm

  • Stage B (intermediate) disease according to the Barcelona Clinic Liver Cancer (BCLC) classification system

    • Unresectable, multinodular asymptomatic tumor
    • No vascular invasion (including segmental portal invasion)
    • No extrahepatic spread
  • Stage C disease (according to the BCLC classification system) with portal vein invasion that is limited to a sub-segmental branch of either the right or left portal vein (i.e., sub-segmental portal vein invasion)
• Being considered for hepatic arterial embolization

• Must have ≥ 1 tumor lesion that can be accurately measured in ≥ 1 dimension according to RECIST criteria

  • The measurable lesion must not have been previously treated with local therapy (e.g., surgery, radiotherapy, radiofrequency ablation, PEI, or cryoablation)
• Child Pugh class A-B7 liver function
• No diffuse HCC
• No unstable ascites

• No known brain metastasis or CNS disease

  • Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 2 mg/dL
• ALT and AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver involvement)
• Creatinine ≤ 1.5 mg/dL
• INR < 1.5 or PT/PTT normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• No cardiac disease, including any of the following:

  • NYHA class III-IV congestive heart failure
  • Unstable angina (anginal symptoms at rest) or new onset angina (within the past 3 months)
  • Myocardial infarction within the past 6 months
• No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• No uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
• No known HIV infection
• No active clinically serious infection > CTCAE grade 2, except hepatitis B or C
• No thrombolic or embolic event (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
• No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks
• No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks
• No clinically significant gastrointestinal bleeding within the past 30 days
• No serious non-healing wound, ulcer, or bone fracture
• No evidence or history of bleeding diathesis or coagulopathy
• No significant traumatic injury within the past 4 weeks
• No known or suspected allergy to sorafenib tosylate or any agent given in the course of this study
• No condition that would impair the ability to swallow whole pills
• No malabsorption problem
• No porto-systemic shunt
• No renal failure
• No severe atheromatosis
• No encephalopathy ≥ grade 1

• No contraindication for any of the following:

  • Arterial procedure (e.g., impaired clotting tests [e.g., platelet count < 50,000/mm³ or prothrombin activity < 50%])
  • Systemic chemotherapy administration (e.g., serum bilirubin > 5 mg/dL, leukocyte count < 3,000/mm³)
  • Sorafenib tosylate administration
• No substance abuse or medical, psychological, or social condition that would interfere with study participation or evaluation of study results
• No other prior or concurrent cancer, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumor (Ta, Tis, or T1), or cancer that was curatively treated > 3 years ago

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior surgery or open biopsy
• No prior systemic chemotherapy or targeted agents
• No concurrent St. John's wort or rifampin
• No concurrent therapy for hepatitis A, B, or C
• Concurrent anti-coagulation with warfarin or heparin allowed