Cediranib Maleate in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Inclusion Criteria:

• Histologically confirmed hepatocellular carcinoma

  • Locally advanced or metastatic disease
  • Not amenable to treatment with surgery or orthotopic liver transplantation

• Measurable or non-measurable disease

  • Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Evidence of disease progression by imaging on serial exams or biochemical evidence of a rising alpha fetoprotein on serial testing

• No history of brain metastases other than locally treatable CNS lesions (i.e., lesions treatable with surgery or radiosurgery)

  • Patients with locally treatable CNS disease eligible provided they were previously treated and had no evidence of CNS progression for ≥ 4 weeks after completion of treatment
• No fibrolamellar hepatocellular carcinoma or mixed cholangiocarcinoma/hepatocellular carcinoma
• Performance status - ECOG 0-1
• Absolute neutrophil count ≥ 1,200/mm^3
• Platelet count ≥ 75,000/mm^3
• Hemoglobin ≥ 10.0 g/dL
• Bilirubin ≤ 3 times upper limit of normal (ULN)
• AST ≤ 5 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Urine protein < 1+ by urine dip stick OR proteinuria < 1 gm/24-hour collection
• QTc prolongation ≤ 500 msec
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled blood pressure, defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg
• No significant ECG abnormality within the past 14 days
• No New York Heart Association class III or IV disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of allergic reaction to compounds of similar chemical or biological composition to AZD2171
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled illness
• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior and no concurrent immunotherapy
• No colony-stimulating factors during the first course of study treatment

• At least 6 weeks since prior chemoembolization

  • Patients must have evidence of disease progression or new metastases after prior chemoembolization
• No prior systemic chemotherapy for this cancer
• No other concurrent chemotherapy
• More than 4 weeks since prior hormonal therapy
• See Disease Characteristics

• At least 6 weeks since prior radiofrequency ablation or other local ablative therapy

  • Patients must have evidence of disease progression or new metastases after prior radiofrequency ablation or other local ablative therapy
• No prior external beam radiotherapy to the primary site
• No prior radiotherapy to ≥ 25% of the bone marrow
• No concurrent radiotherapy
• See Disease Characteristics
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs or biologics with proarrhythmic potential