Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

NCT ID: NCT00612430

Last Updated: 2013-08-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2011-09-30

Brief Summary

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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

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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.

Conditions

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Glioblastoma Gliosarcoma

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Bevacizumab and Etoposide

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Bevacizumab - Avastin Etoposide-Etopophos-Toposar-VePesid-VP-16

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David A. Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

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Duke University Health System

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 19920819 (View on PubMed)

Related Links

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

The Preston Robert Tisch Brain Tumor Center at DUKE

Other Identifiers

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Pro00000379

Identifier Type: -

Identifier Source: org_study_id