Clinical trial NCT00612430: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-02-11
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 6 Month Progression-Free Survival (PFS)
timeFrame: 6 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 2 years
measure: Safety of Study Treatment Regimen
timeFrame: 2 years
measure: Median Progression-Free Survival
timeFrame: Patients were followed for a median of 91.4 weeks
measure: Median Overall Survival (OS)
timeFrame: median of 91.4 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: David A. Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.