Gemcitabine, Oxaliplatin in Combination With Bevacizumab in Patients With Hepatocellular Carcinoma

• Treatment is given in cycles, each cycle (except for cycle 1) is 4 weeks long. Cycle 1 is only 2 weeks long.
• During cycle one only, bevacizumab will be given intravenously on day one. Two weeks after receiving bevacizumab, the patient will return to the clinic for treatment with all 3 study drugs.
• During cycle 2 and every cycle thereafter patients will receive; bevacizumab intravenously on day one and day 15; gemcitabine intravenously on day 2 and day 16; oxaliplatin intravenously on day 2 and day 16.
• The following evaluations will be conducted on day 1 and day 15 of each cycle (once every 2 weeks): physical examination, vital signs, medical history, blood tests and urine tests.
• Tumor measurements done by CT and/or MRI will be repeated at the end of cycle 3 and every 2 cycles thereafter.
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) of the liver and Perfusions CT scans will also be done on days 10-12 following bevacizumab treatment during cycle 1, and the Perfusion CT will be repeated at the end of cycle 3.
• Once study treatment is stopped the following evaluations will be performed: physical exam, vital signs, blood work, urine tests, CT scan of chest, abdomen and pelvis, and tumor measurements by CT or MRI scans.
• Follow-up will consist of physical examinations and blood tests every 6 months.
• Patients will continue to receive study treatment as long as there is no disease progression or unacceptable side affects.

Inclusion criteria

• Unresectable or metastatic hepatocellular carcinoma
• Measurable tumors
• Adequate hepatic function: total bilirubin < 3.0mg/dl; AST < 7x ULN
• Adequate bone marrow function: ANC > 1,000/mm3; platelets > 75,000/mm3
• INR < 1.5 for those who are not on anticoagulation
• Up to two prior chemotherapy regimens for hepatocellular carcinoma
• 18 years of age or older
• ECOG performance status of 0-1
• Life expectancy of > 12 weeks

Exclusion criteria

• Clinically apparent central nervous system metastases or carcinomatous meningitis
• Uncontrolled serious medical or psychiatric illness
• Pregnant or lactating women
• Current or recent (within 4 weeks of first study infusion) participation in experimental study drug
• Uncontrolled hypertension
• Significant proteinuria
• Serious, non-healing wound, ulcer, or bone fracture
• Evidence of bleeding diathesis or coagulopathy