Safety of Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma: A Pilot Study

Inclusion Criteria:

- Recurrent malignant glioma that has failed prior radiotherapy and/or chemotherapy.
Surgery for the recurrence may be offered to selected patients prior to receiving
bevacizumab and IMRT on this protocol.

- MRI scan with gadolinium contrast showing geographically-circumscribed tumor < than
or equal to 3.5cm. (Scan must be performed on a steroid dosage that has been stable
for at least 5 days. If the steroid dose is increased between date of imaging and
registration, a new baseline MRI is required).

- Patients must have recovered from the toxic effects of prior therapy:

- An interval of > than or equal to 4 weeks (28 days) from prior cytotoxic therapy

- An interval of > than or equal to 1 week (7 days) from any non-cytotoxic agents

- An interval of > than or equal to 6 weeks (42 days) from the completion of radiation
therapy

- Absolute neutrophil count > than or equal to 1,500/mm3.

- Platelet count > than or equal to 100,000/mm3.

- Hemoglobin > than or equal to 10 g/dl.

- BUN and serum creatinine both < 1.5 times upper limit of normal.

- Total bilirubin both < 1.5 times upper limit of normal.

- SGOT and SGPT both < than or equal to 3 times upper limit of normal.

- Alkaline phosphatase < than or equal to 2 times upper limit of normal.

- > than or equal to 18 years of age.

- Karnofsky Performance Score > or equal to 70

- Life expectancy > or equal to 12 weeks

- Men and women with reproductive potential must agree to use an acceptable method of
birth control during treatment and for six months after completion of treatment.

- Patient or their legal proxy must provide written informed consent prior to
registration on study.

Exclusion Criteria:

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study.

- Blood pressure >150 mmHg systolic and/or >100 mmHg diastolic

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- Unstable angina within 12 months of study enrollment

- CTC 3.0 Grade 2 or greater congestive heart failure

- History of myocardial infarction within 12 months of study enrollment

- History of stroke or transient ischemic attack at any time

- Known CNS disease

- Known hypersensitivity to any component of bevacizumab

- History of peptic ulcer within the last 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Use of ongoing anticoagulants or antiplatelet agents (aspirin, NSAIDS, etc)

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to the first dose of bevacizumab or anticipation of need for major surgical
procedure during the course of the study. (Recently resected patients may be enrolled
on-study two weeks post-surgery. However, treatment with Bevacizumab will not begin
until 28 days after the surgical procedure for all patients.)

- Craniotomy wound that has not sufficiently healed

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to study enrollment

- Pregnant (positive pregnancy test) or lactating

- Urine protein:creatinine ratio ≥1.0 at screening

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment

- Serious, non-healing wound, ulcer, or bone fracture

- Lung carcinoma of squamous cell histology or any histology in close proximity to a
major vessel, cavitation, or history of hemoptysis

- Inability to comply with study and/or follow-up procedures

- Glioma showing prior spontaneous hemorrhage as determined from the clinical history
or from any preoperative CT or MRI scan.