Sunitinib in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

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