Inclusion Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

- Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma
(HCC) meeting 1 of the following criteria:

- Localized, surgically unresectable disease

- Candidates for radical surgery for locally advanced disease are excluded

- Metastatic disease

- Measurable disease, defined as ≥ 1 lesion, outside of pretreated areas, that can be
measured in ≥ 1 dimension as ≥ 10 mm by spiral or multi-slice CT scan or MRI

- Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction

Exclusion criteria:

- Clinical ascites of any grade

- Clinical symptoms or history of CNS metastases or leptomeningeal disease

- Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC

PATIENT CHARACTERISTICS:

Inclusion criteria:

- WHO performance status 0-1

- Hemoglobin ≥ 9.0 g/dL

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Bilirubin ≤ 2 times upper limit of normal (ULN)

- ALT ≤ 7 times ULN

- Albumin ≥ 2.5 g/dL

- Creatinine clearance ≥ 40 mL/min

- Quick test ≥ 50% (adequate coagulation)

- Urine dipstick for proteinuria < 2+ OR ≤ 1 g of protein in 24-hour urine collection

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study therapy

Exclusion criteria:

- Pregnant or nursing

- Encephalopathy

- Malignancy within the past 5 years except for adequately treated cervical carcinoma
in situ or localized nonmelanoma skin cancer

- Hemorrhagic or thrombotic cerebrovascular event in the past 12 months

- Documented variceal hemorrhage within the past 3 months

- History or presence of clinically significant acute or unstable cardiovascular,
cerebrovascular, renal, gastrointestinal, pulmonary, immunological (except for the
presence of hepatitis B virus, hepatitis C virus, or cirrhosis), endocrine, or
central nervous system disorders

- Known HIV infection

- Active infection requiring IV antibiotics

- Arterial hypertension ≥ 150/100 mm Hg, despite therapy

- Ongoing cardiac dysrhythmias ≥ grade 2

- Atrial fibrillation of any grade

- Prolongation of QTc > 500 msec in screening ECG or history of familial long QT
syndrome

- Inability to take oral medications

- Psychiatric disorder precluding understanding of information of study-related topics,
giving informed consent, or interfering with compliance for oral drug intake

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

- At least 4 weeks since prior surgery or liver-directed therapy (e.g., transarterial
embolization/chemoembolization [limited to 5 treatments], radiofrequency ablation,
cryoablation, radiotherapy, or percutaneous ethanol injection)

- Previously treated lesions must remain separate from those to be measured in the
present study

- Low-dose anticoagulants for maintenance of patency of central venous access or
prevention of deep vein thrombosis allowed

Exclusion criteria:

- Prior systemic anticancer treatment for hepatocellular carcinoma

- Prior organ transplantation

- Treatment in a clinical study within the past 30 days

- Concurrent full-dose anticoagulant or requirement for anticoagulant therapy

- Concurrent experimental drugs or other anticancer therapy

- Concurrent use or anticipated need for CYP3A4 inhibitors (e.g., ketoconazole,
itraconazole, voriconazole, erythromycin, clarithromycin, and protease inhibitors)

- Concurrent CYP3A4 inducers (e.g., carbamazepine, continuous treatment with
dexamethasone [> 2 mg/day for > 7 days], phenobarbital, phenytoin, rifampicin, and St
John's wort)

- Concurrent antacids allowed provided they are administered > 1 hour before or >
1 hour after study drug

- Concurrent elective major surgery

- Concurrent radiotherapy

- Concurrent analgesic radiotherapy of nontarget lesions allowed