Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer

Inclusion Criteria

• Histologically confirmed hepatocellular carcinoma
• Confirmed by needle aspirate, biopsy, or prior surgical resection specimen
• Clinically confirmed hepatocellular carcinoma defined as follows:
• Cirrhosis or chronic hepatitis B or C virus infection, with 1 or more hypervascular liver masses more than 2 cm
• Alpha-fetoprotein (AFP) greater than 400 ng/mL OR greater than 3 times normal and doubling in value during the past 3 months
• Deemed unresectable
• Prior surgical resection allowed
• Recurrence after hepatic resection or other procedure allowed
• Tumor that extends into branches of the portal or hepatic veins allowed
• No tumor invading the main portal vein (portal trunk) or inferior vena cava
• No tumor occupying more than 50% of the liver volume
• Enlargement/involvement of regional lymph nodes allowed
• At least 1 unidimensionally measurable lesion at least 20 mm
• No poorly defined lesions
• No vague hypervascular patches
• Child-Pugh class A or compensated Child-Pugh class B liver dysfunction
• No Child-Pugh class C or uncompensated class B indicated by active encephalopathy, persistent ascites, or prothrombin time greater than 1.5 times normal
• Prior ascites allowed if manageable with diuretics alone
• No repeated paracentesis (more than 1 per month)
• No extrahepatic metastasis
• No documented brain metastases
• No history or clinical evidence of CNS disease (e.g., primary brain tumor, seizures uncontrolled with standard medical therapy, or history of stroke)
• Performance status - ECOG 0-2
• Absolute neutrophil count greater than 1,500/mm^3
• Hemoglobin at least 8 g/dL
• Platelet count at least 75,000/mm^3
• No prior serious bleeding event (unrelated to liver disease)
• No bleeding diathesis
• No coagulopathy
• Bilirubin no greater than 3 mg/dL
• Transaminases less than 5 times upper limit of normal (ULN)
• Albumin at least 2.5 mg/dL
• PTT less than 4 seconds above ULN
• INR less than 1.5 (for patients receiving warfarin)
• Creatinine less than 1.5 g/dL
• Urine protein less than 500 mg/24hrs*

Exclusion criteria

• No thromboembolic event within the past 12 months
• No clinically significant cardiovascular disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring parenteral antibiotics
• No serious non-healing wound/ulcer or bone fracture
• No variceal bleeding within the past 6 months
• No malignancy within the past 5 years except localized nonmelanoma skin cancer
• No ongoing psychiatric or social situation that would preclude study compliance
• No known hypersensitivity to Chinese hamster ovary cell products
• No known hypersensitivity to other recombinant human antibodies
• No more than 1 prior biologic therapy
• No concurrent interferon
• No concurrent interleukin-2
• No more than 1 prior antineoplastic chemotherapy
• At least 4 weeks since prior invasive surgery, including open biopsy
• At least 2 weeks since prior needle biopsy (core or fine-needle aspirate)
• No concurrent hepatic transplant
• At least 4 weeks since prior anticancer therapy
• No concurrent platelet-stimulating factors (e.g., oprelvekin)
• No concurrent full-dose anticoagulants or thrombolytic agents (except as required to maintain patency of pre-existing, permanent indwelling IV catheters)
• No chronic daily antiplatelet drugs (e.g., aspirin doses of 325 mg/day or higher or non-steroidal anti-inflammatory drugs)