Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme

Inclusion Criteria:

1. Histologically confirmed glioblastoma multiforme, WHO grade IV astrocytoma.
2. Prior first-line treatment with surgery or biopsy followed by fractionated radiotherapy with concurrent temozolomide-containing chemotherapy is required for glioblastoma patients. Additional prior chemotherapy is allowed, without limitation on number of recurrences.
3. An interval of at least 2 months since completion of fractionated radiotherapy.
4. Age \> 18 years
5. Life expectancy of at least 12 weeks.
6. Karnofsky Performance Status score (KPS) of ≥ 60
7. Documented recurrent disease; Disease must be evaluable, but does not need to be measurable; the target site for SRS does not need to be located in a previously-irradiated area.
8. All patients must have no restrictions to obtaining MRI with and without gadolinium contrast.
9. Adequate bone marrow, hepatic and renal function ; BUN \< 25 and Cr \< 1.7
10. Negative pregnancy test at the time of SRS in any patient who could be pregnant.
11. Willingness to forego additional therapy until evidence of disease progression

Exclusion Criteria:

1\. General Medical Exclusions:

1. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
2. Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last 3 years.
3. Prior radiosurgery
4. Prior intracavitary irradiation or Gliadel wafers.

2\. Disease-Specific Exclusions:

1. Inability to comply with protocol or study procedures
2. Prior treatment with bevacizumab.
3. Inability to undergo MRI with and without contrast administration.

3\. Bevacizumab-Specific Exclusions:

1. Inadequately controlled hypertension.
2. Prior history of hypertensive crisis or hypertensive encephalopathy.
3. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
4. History of myocardial infarction or unstable angina within 6 months prior to Day 1.
5. History of stroke or transient ischemic attack within 6 months prior to Day 1.
6. Significant vascular disease within 6 months prior to Day 1.
7. History of hemoptysis within 1 month prior to Day 1.
8. Evidence of bleeding diathesis or significant coagulopathy
9. Major surgical procedure, open biopsy, or significant traumatic injury within 14 days prior to Day 1 or anticipation of need for major non -cranial surgical procedure during the course of the study.
10. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.
11. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
12. Serious, non-healing wound, active ulcer, or untreated bone fracture.
13. Proteinuria
14. Known hypersensitivity to any component of bevacizumab
15. Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential.