Bi-weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of a glioblastoma multiforme/gliosarcoma and:

* Must have completed at least 2 cycles of adjuvant chemotherapy
* Age \> 18 years
* Karnofsky \> 60%
* Hematocrit \> 29%, ANC \> 1,500 cells/dl, platelets \> 125,000 cells/dl
* Serum creatinine \< 1.5 mg/dl, BUN \< 25 mg/dl, serum SGOT and bilirubin \< 1.5 times upper limit of normal
* If on corticosteroids, must be on a stable dose for 1 week prior to entry; if clinically possible, the dose should not be escalated over entry dose level
* Signed informed consent approved by the Institutional Review Board prior to study entry
* If sexually active, will take contraceptive measures for the duration of the treatments

Exclusion Criteria:

* Prior toxicity grade ≥ 3 with TMZ
* Prior treatment with bevacizumab
* Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control
* Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
* Acute or chronic liver disease (i.e., hepatitis, cirrhosis)
* Confirmed diagnosis of HIV infection
* Have received investigational drugs less than 4 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy
* Have received chemotherapy within 2 weeks prior (6 weeks for nitrosourea) to entry on this study, or who have not recovered from the toxic effects of such therapy
* Have received biologic, immunotherapeutic or cytostatic agents within 1 week prior to entry on this study or who have not recovered from the toxic effects of such therapy
* Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant
* Have received radiation therapy within 2 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy.
* Surgical resection of brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
* Have had any surgery other than resection of a brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
* Unwilling to or unable to comply with the protocol
* Evidence of tumor progression within on immediate post radiation brain imaging
* Have not received at least 2 cycles of adjuvant chemotherapy
* Life expectancy of less than 12 weeks
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

Bevacizumab-Specific Exclusions:

* Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
* History of myocardial infarction or unstable angina within 6 months
* History of stroke or transient ischemic attack within 6 months
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days
* History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
* Serious, non-healing wound, active ulcer, or untreated bone fracture.
* Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening
* Known hypersensitivity to any component of bevacizumab