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

This is an interventional treatment trial for Liver Cancer focused on measuring adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer Read More

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