Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan
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
Drug: Temo + Avastin
Drug: VP-16 + Avastin
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan|
- The Primary Outcome Measure is 6 Month Progression-free Survival. [ Time Frame: 6 months ] [ Designated as safety issue: No ]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.
- Radiographic Response [ Time Frame: 41 months ] [ Designated as safety issue: No ]Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
- Median Progression-free Survival (PFS) [ Time Frame: 41 months ] [ Designated as safety issue: No ]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 Frame: 41 months ] [ Designated as safety issue: No ]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. [ Time Frame: 41 months ] [ Designated as safety issue: Yes ]Incidence of ≥Grade 3 treatment related, non-hematologic toxicity
|Study Start Date:||April 2008|
|Study Completion Date:||January 2011|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Experimental: Temo + Avastin
Patients treated with bevacizumab + temozolomide
Drug: 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.
Experimental: VP-16 + Avastin
Patients treated with bevacizumab and VP-16 (etoposide)
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00613028
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A. Reardon, MD||Duke University Health System|