Bevacizumab (RhuMAB-VEGF) In Hepatocellular Cancer For Patients With Unresectable Tumor (Without Invasion Of The Main Portal Vein Or Metastatic Disease) A Phase II Study
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 (porta-hepatis) 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*
- No thromboembolic event within the past 12 months including the following:
- Stroke
- Myocardial infarction
- Transient ischemic attack
- Angina
- No clinically significant cardiovascular disease including the following:
- Uncontrolled hypertension
- Unstable angina
- Congestive heart failure (New York Heart Association grade II-IV)
- Serious cardiac arrhythmia requiring medication
- Grade II or greater peripheral vascular disease within the past year
- No deep vein thrombosis within the past year
- No pulmonary embolus within the past year
- 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
- Prior esophageal varices allowed provided the following criteria are met:
- Specific therapy (i.e., banding or sclerotherapy) has been received
- No bleeding within the past 6 months
- Varices remaining obliterated, minimal, or grade 1 (involving less than 33%
of luminal diameter)* by re-endoscopy within the past 4 weeks
- 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)
