Ph II Bevacizumab + Etoposide for Pts w Recurrent MG
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Bevacizumab and Etoposide
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.
Intervention MeSH terms: Bevacizumab; Etoposide; Etoposide phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; GBM; MG; Brain tumor; Bevacizumab; Avastin; Etoposide; VP-16; Etopophos; Toposar; VePesid; Glioblastoma multiforme; Recurrent GBM; Anaplastic astrocytoma; Malignant glioma

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.
    

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