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

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: Genentech, Inc.
• Treatments: Bevacizumab; Dacarbazine; Etoposide; Etoposide phosphate; Irinotecan; Temozolomide

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