ph ii bev + either temozolomide/etoposide for gbm pts who have failed bev + irinotecan

Conditions: Glioblastoma; Gliosarcoma

Summary: 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

Keywords: glioblastoma gliosarcoma gbm bevacizumab avastin etoposide brain tumor irinotecan glioblastoma multiforme temodar temozolomide etopophos toposar vepesid vp-16 camptosar