A Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN)

Inclusion Criteria: * Signed Informed Consent Form * Age ≥ 18 years * Histologically confirmed GBM in first or second relapse * Radiographic demonstration of disease progression following prior therapy * Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment (Day 0) * An interval of ≥ 4 weeks since prior surgical resection * Prior standard radiation for GBM * Prior chemotherapy: first-relapse subjects * Prior chemotherapy: second-relapse subjects * Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field * Prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field * Karnofsky performance status ≥ 70 * Life expectancy \> 12 weeks * Use of an effective means of contraception in males and in females of childbearing potential * Ability to comply with study and follow-up procedures Exclusion Criteria: * Prior treatment with irinotecan, bevacizumab, or another VEGF or VEGFR-targeted agent * Prior treatment with prolifeprospan 20 with carmustine wafer * Prior intracerebral agents * Need for urgent palliative intervention for primary disease (e.g., impending herniation) * Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: Presence of hemosiderin; Resolving hemorrhagic changes related to surgery; Presence of punctate hemorrhage in the tumor * Received more than two treatment regimens for Grade III and/or Grade IV glioma * Blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic * History of hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater CHF * History of myocardial infarction or unstable angina within 6 months prior to Day 0 * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 0 * Evidence of bleeding diathesis or coagulopathy * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * History of intracerebral abscess within 6 months prior to Day 0 * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 0 * Serious non-healing wound, ulcer, or bone fracture * Pregnancy (positive pregnancy test) or lactation * Known hypersensitivity to any component of bevacizumab * History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix) * Pregnant or nursing females * Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication * Subjects unable to undergo an MRI with contrast