Cisplatin or Carboplatin and Sorafenib in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• To assess the safety of intrahepatic arterial infusion of cisplatin or carboplatin in combination with sorafenib tosylate in patients with unresectable hepatocellular carcinoma.

Secondary

• To assess the time to tumor progression in patients treated with this regimen.
• To assess the overall and progression-free survival of patients treated with this regimen.

OUTLINE: Patients receive intrahepatic arterial infusion of cisplatin or carboplatin over 30-45 minutes on day 1 and oral sorafenib tosylate twice daily on days 8-35. Treatment repeats every 42 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatocellular carcinoma (HCC) OR serum alpha fetoprotein ≥ 400 ng/mL with radiological evidence suggestive of HCC

• Unresectable disease
• Child-Pugh class A or selected Child-Pugh class B disease (Child-Pugh score ≤ 7 points)

• No Child-Pugh class C disease
• No disease outside the liver or macroscopic invasion of the major vessels such as the portal vein
• No known brain metastasis

• Patients with neurological symptoms must undergo CT scan or MRI of the brain

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• WBC ≥ 3,000/mm³ (for patients scheduled to receive carboplatin) or ≥ 2,000/mm³ (for patients scheduled to receive cisplatin)
• Platelet count ≥ 100,000/mm³ (for patients scheduled to receive carboplatin) or ≥ 60,000/mm³ (for patients scheduled to receive cisplatin)
• Serum creatinine ≤ 1.9 mg/dL (for patients scheduled to receive carboplatin) or ≤ 1.5 mg/dL (for patients scheduled to receive cisplatin)
• Serum total bilirubin ≤ 3 mg/dL
• AST and ALT < 5 times upper limit of 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)
• New onset of angina within the past 3 months
• Myocardial infarction within the past 6 months
• 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 thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
• No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks
• No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
• No evidence or history of bleeding diathesis or coagulopathy
• No evidence of encephalopathy
• No condition that would impair the ability to swallow whole pills
• No history of malabsorption problems
• No significant traumatic injury within the past 4 weeks
• No serious non-healing wound, ulcer, or bone fracture
• No active clinically serious infection
• No known HIV infection
• No known or suspected allergy to sorafenib tosylate or any other study agent

PRIOR CONCURRENT THERAPY:

• No prior cisplatin, carboplatin, or sorafenib tosylate
• No prior systemic chemotherapy for HCC
• No other prior systemic or locoregional therapy
• More than 4 weeks since prior major surgery or open biopsy
• No concurrent St. John's wort or rifampin