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

Primary Purpose

Glioblastoma, Gliosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Temo + Avastin
VP-16 + Avastin
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Gliosarcoma, GBM, Bevacizumab, Avastin, Etoposide, Brain tumor, Irinotecan, Glioblastoma multiforme, Temodar, Temozolomide, Etopophos, Toposar, VePesid, VP-16, Camptosar

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Duke University Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Temo + Avastin

VP-16 + Avastin

Arm Description

Patients treated with bevacizumab + temozolomide

Patients treated with bevacizumab and VP-16 (etoposide)

Outcomes

Primary Outcome Measures

The Primary Outcome Measure is 6 Month Progression-free Survival.
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

Secondary Outcome Measures

Radiographic Response
Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
Median Progression-free Survival (PFS)
Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
Median Overall Survival (OS)
Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Incidence of ≥Grade 3 treatment related, non-hematologic toxicity

Full Information

First Posted
January 29, 2008
Last Updated
July 10, 2013
Sponsor
Duke University
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00613028
Brief Title
Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan
Official Title
Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma
Keywords
Glioblastoma, Gliosarcoma, GBM, Bevacizumab, Avastin, Etoposide, Brain tumor, Irinotecan, Glioblastoma multiforme, Temodar, Temozolomide, Etopophos, Toposar, VePesid, VP-16, Camptosar

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temo + Avastin
Arm Type
Experimental
Arm Description
Patients treated with bevacizumab + temozolomide
Arm Title
VP-16 + Avastin
Arm Type
Experimental
Arm Description
Patients treated with bevacizumab and VP-16 (etoposide)
Intervention Type
Drug
Intervention Name(s)
Temo + Avastin
Other Intervention Name(s)
temozolomide, temodar, bevacizumab
Intervention Description
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
Intervention Name(s)
VP-16 + Avastin
Other Intervention Name(s)
VP-16, etoposide, bevacizumab, avastin
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Primary Outcome Measure is 6 Month Progression-free Survival.
Description
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Radiographic Response
Description
Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
Time Frame
41 months
Title
Median Progression-free Survival (PFS)
Description
Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
Time Frame
41 months
Title
Median Overall Survival (OS)
Description
Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Time Frame
41 months
Title
Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Description
Incidence of ≥Grade 3 treatment related, non-hematologic toxicity
Time Frame
41 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A. Reardon, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.cancer.duke.edu/btc/
Description
The Preston Robert Tisch Brain Tumor Center at DUKE

Learn more about this trial

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

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