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

Duke University

Status and phase

Completed

Phase 2

Conditions

Glioblastoma

Gliosarcoma

Treatments

Drug: VP-16 + Avastin

Drug: Temo + Avastin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00613028

Pro00003768

Details and patient eligibility

About

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

Full description

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.

Enrollment

23 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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