search
Back to results

Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

Primary Purpose

Glioblastoma, Gliosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab and Etoposide
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, MG, Brain tumor, Bevacizumab, Avastin, Etoposide, VP-16, Etopophos, Toposar, VePesid, Glioblastoma multiforme, Recurrent GBM, Anaplastic astrocytoma, Malignant glioma

Eligibility Criteria

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

Inclusion Criteria:

  • Pts have confirmed diagnosis of recurrent/progressive WHO gr III & IV MG
  • Age >18 rs
  • Interval of >4 wks since prior surgery
  • Interval of >4 wks since prior XRT/chemo, unless there is unequivocal evidence of progressive disease & pts have recovered from all anticipated toxicity of most recent therapy;
  • Karnofsky performance status score >60
  • Hematocrit >29 percent, ANC >1,500 cells/microliter, platelets >100,000 cells/microliter
  • Serum creatinine <1.5 mg/dl, BUN <25 mg/dl, serum SGOT & bilirubin <1.5 x ULN
  • For pts on corticosteroids, they have been on astable dose for 1wk prior to entry
  • Signed informed consent approved by IRB prior to pt entry
  • If sexually active, pts must agree to take contraceptive measures for duration of treatments.

Exclusion Criteria:

  • Prior therapy w either bevacizumab/etoposide
  • >3 prior recurrences
  • Pregnancy/breast feeding
  • Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
  • Evidence of CNS hemorrhage on baseline MRI on CT scan
  • Pts who require therapeutic anti-coagulation
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state
  • Pts w another primary malignancy that has required treatment <past year

Sites / Locations

  • Duke University Health System

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab + Etoposide

Arm Description

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.

Outcomes

Primary Outcome Measures

6 Month Progression-Free Survival (PFS)
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.

Secondary Outcome Measures

Objective Response Rate
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
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 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 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.

Full Information

First Posted
January 29, 2008
Last Updated
July 30, 2013
Sponsor
Duke University
Collaborators
Genentech, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT00612430
Brief Title
Ph II Bevacizumab + Etoposide for Pts w Recurrent MG
Official Title
Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 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 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.
Detailed Description
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.

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, MG, Brain tumor, Bevacizumab, Avastin, Etoposide, VP-16, Etopophos, Toposar, VePesid, Glioblastoma multiforme, Recurrent GBM, Anaplastic astrocytoma, Malignant glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab + Etoposide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab and Etoposide
Other Intervention Name(s)
Bevacizumab - Avastin, Etoposide-Etopophos-Toposar-VePesid-VP-16
Intervention Description
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.
Primary Outcome Measure Information:
Title
6 Month Progression-Free Survival (PFS)
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. 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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
2 years
Title
Safety of Study Treatment Regimen
Description
Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.
Time Frame
2 years
Title
Median Progression-Free Survival
Description
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.
Time Frame
Patients were followed for a median of 91.4 weeks
Title
Median Overall Survival (OS)
Description
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.
Time Frame
median of 91.4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pts have confirmed diagnosis of recurrent/progressive WHO gr III & IV MG Age >18 rs Interval of >4 wks since prior surgery Interval of >4 wks since prior XRT/chemo, unless there is unequivocal evidence of progressive disease & pts have recovered from all anticipated toxicity of most recent therapy; Karnofsky performance status score >60 Hematocrit >29 percent, ANC >1,500 cells/microliter, platelets >100,000 cells/microliter Serum creatinine <1.5 mg/dl, BUN <25 mg/dl, serum SGOT & bilirubin <1.5 x ULN For pts on corticosteroids, they have been on astable dose for 1wk prior to entry Signed informed consent approved by IRB prior to pt entry If sexually active, pts must agree to take contraceptive measures for duration of treatments. Exclusion Criteria: Prior therapy w either bevacizumab/etoposide >3 prior recurrences Pregnancy/breast feeding Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil Evidence of CNS hemorrhage on baseline MRI on CT scan Pts who require therapeutic anti-coagulation Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state Pts w another primary malignancy that has required treatment <past year
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

Citations:
PubMed Identifier
19920819
Citation
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer. 2009 Dec 15;101(12):1986-94. doi: 10.1038/sj.bjc.6605412. Epub 2009 Nov 17.
Results Reference
derived
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 Bevacizumab + Etoposide for Pts w Recurrent MG

We'll reach out to this number within 24 hrs