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

NCT ID: NCT00613028

Last Updated: 2013-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-01-31

Brief 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

Detailed 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.

Conditions

Glioblastoma; Gliosarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temo + Avastin

Patients treated with bevacizumab + temozolomide

Group Type: EXPERIMENTAL

Temo + Avastin

Intervention Type: DRUG

Patients have progressed/had gr3/\> toxicity related to etoposide, with no had progression/gr 3/\> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.

VP-16 + Avastin

Patients treated with bevacizumab and VP-16 (etoposide)

Group Type: EXPERIMENTAL

VP-16 + Avastin

Intervention Type: DRUG

Patients have progressed/had gr3/\> toxicity related to temozolomide, but have not progressed/gr3/\> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.

Interventions

Temo + Avastin

Patients have progressed/had gr3/\> toxicity related to etoposide, with no had progression/gr 3/\> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.

Intervention Type: DRUG

VP-16 + Avastin

Patients have progressed/had gr3/\> toxicity related to temozolomide, but have not progressed/gr3/\> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

temozolomide; temodar; bevacizumab; VP-16; etoposide; bevacizumab; avastin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David A. Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Duke University Health System

Durham, North Carolina, United States

Countries

United States

Related Links

http://www.cancer.duke.edu/btc/

The Preston Robert Tisch Brain Tumor Center at DUKE

Other Identifiers

Pro00003768

Identifier Type: -

Identifier Source: org_study_id