Ph II Bevacizumab + Etoposide for Pts w Recurrent MG

Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma

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.

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.

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