Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan

Primary objective To estimate 6-month progression free survival probability of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety \& tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To evaluate radiographic response, progression free survival \& overall survival of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan

This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide \& approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I \& II error rates associated w testing are 0.030 \& 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, \& bev.

Eligibility Criteria:
Inclusion Criteria:

* Pts have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy w bev + irinotecan
* Age \>18 yrs
* Interval of \>4 wks between prior surgical resection/1 week from stereotactic biopsy
* Interval of \>12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on \>2 consecutive MRI scans \>4wks apart, /there is biopsy-proven tumor progression
* Interval of \>4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Hematocrit \>29percent, absolute neutrophil count (ANC)\>1,000 cells/ml l, platelets \> 100,000 cells/ml l
* Serum creatinine\<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) \& bilirubin\<1.5 times upper limit of normal (ULN)
* Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
* No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1
* If sexually active, pts will take contraceptive measures for duration of treatments

Exclusion Criteria:

* Co-medication that may interfere w study results
* Active infection requiring intravenous antibiotics
* Progression to daily etoposide/progression to daily temo
* Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide
* Requires therapeutic anti-coagulation with warfarin.
* Inability to comply w study and/or follow-up procedures
* Current, recent,/planned participation in experimental drug study other than Genentech-sponsored bev cancer study
* Inadequately controlled hypertension
* Any prior history of hypertensive crisis/hypertensive encephalopathy
* New York Heart Association (NYHA) Gr II/greater congestive heart failure
* History of myocardial infarction (MI)/unstable angina within 6 mths prior to study enrollment
* History of stroke/transient ischemic attack within 6 mths prior to study enrollment
* Significant vascular disease
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment 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 prior to study enrollment
* 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
* Proteinuria at screening as demonstrated by either:
* urine protein:creatinine (UPC) ratio \>1.0 at screening /
* Urine dipstick for proteinuria ≥ 2+
* Known hypersensitivity to any component of bevacizumab
* Pregnant or lactating. Use of effective means of contraception in subjects of child-bearing potential