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