Ph II Bevacizumab + Etoposide for Pts w Recurrent MG
Primary Objective to estimate 6-month progression free survival probability of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
Secondary Objectives To evaluate safety & tolerability of Etoposide + Bevacizumab among patients with recurrent malignant glioma (RMG).
To evaluate radiographic response, progression free survival & overall survival of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma|
- 6 Month Progression-Free Survival (PFS) [ 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. Progression was defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans.
- Objective Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]The percentage of participants with complete or partial response as determined by the following criteria: complete response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination; partial response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination. A confirmation of response was not required.
- Safety of Study Treatment Regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.
- Median Progression-Free Survival [ Time Frame: Patients were followed for a median of 91.4 weeks ] [ Designated as safety issue: No ]Time in weeks from the start of study treatment to the date of first progression, 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: median of 91.4 weeks ] [ Designated as safety issue: No ]Time in weeks 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.
|Study Start Date:||March 2007|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
Experimental: Bevacizumab + Etoposide
Grade III and IV patients will receive: Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If patient tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day.
Drug: Bevacizumab and Etoposide
32 pts w recurrent WHO grade III MG & 27 pts w recurrent WHO grade IV MG will be enrolled in this study. Estimated rate of accrual is 10 pts per month. The estimated date of study completion is 6-9 months from study initiation. Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If pt tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. The Duke investigators will review all la data & order treatment. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent.
Exploratory, single-arm, ph II study designed to assess anti-tumor activity of combinatorial regimen consisting of Etoposide + Bevacizumab among patients with RMG. Primary endpoint of study is probability of progression-free survival at 6 months. Important secondary objective is to further assess safety of Etoposide & Bevacizumab for patients with recurrent malignant glioma.
If study demonstrates that combinatorial regimen of Etoposide + Bevacizumab is associated with encouraging anti-tumor activity among patients with RMG, further assessment of regimen in additional phase II & possibly phase III studies, will be considered.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00612430
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A. Reardon, MD||Duke University Health System|