Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Bevacizumab + Etoposide	Bevacizumab and 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.

Primary Outcome Measures

Name	Time	Method
6 Month Progression-Free Survival (PFS)	6 months	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

Name	Time	Method
Objective Response Rate	2 years	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	2 years	Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.
Median Progression-Free Survival	Patients were followed for a median of 91.4 weeks	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)	median of 91.4 weeks	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.