Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Temo + Avastin; VP-16 + Avastin
Intervention description: Patients have progressed/had gr3/> toxicity related to etoposide, with no had progression/gr 3/> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.; Patients have progressed/had gr3/> toxicity related to temozolomide, but have not progressed/gr3/> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.
Intervention MeSH terms: Bevacizumab; Etoposide; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; GBM; Bevacizumab; Avastin; Etoposide; Brain tumor; Irinotecan; Glioblastoma multiforme; Temodar; Temozolomide; Etopophos; Toposar; VePesid; VP-16; Camptosar

Summary:

      Primary objective To estimate 6-month progression free survival probability of pts w
      recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on
      bev + irinotecan Secondary Objectives To evaluate safety & tolerability of bev + either daily
      temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To
      evaluate radiographic response, progression free survival & overall survival of pts w
      recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on
      bev + irinotecan
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pts have confirmed diagnosis of GBM & radiographic evidence of recurrence following
             prior therapy w bev + irinotecan

          -  Age >18 yrs

          -  Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy

          -  Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless
             there is new area of enhancement consistent w recurrent tumor outside of XRT
             field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart,
             /there is biopsy-proven tumor progression

          -  Interval of >4 wks from prior chemo / investigational agent unless pt has recovered
             from all anticipated toxicities associated w that therapy.

          -  Eastern Cooperative Oncology Group (ECOG) 0-1

          -  Hematocrit >29percent, absolute neutrophil count (ANC)>1,000 cells/ml l, platelets >
             100,000 cells/ml l

          -  Serum creatinine<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) &
             bilirubin<1.5 times upper limit of normal (ULN)

          -  Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry

          -  No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1

          -  If sexually active, pts will take contraceptive measures for duration of treatments

        Exclusion Criteria:

          -  Co-medication that may interfere w study results

          -  Active infection requiring intravenous antibiotics

          -  Progression to daily etoposide/progression to daily temo

          -  Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide

          -  Requires therapeutic anti-coagulation with warfarin.

          -  Inability to comply w study and/or follow-up procedures

          -  Current, recent,/planned participation in experimental drug study other than
             Genentech-sponsored bev cancer study

          -  Inadequately controlled hypertension

          -  Any prior history of hypertensive crisis/hypertensive encephalopathy

          -  New York Heart Association (NYHA) Gr II/greater congestive heart failure

          -  History of myocardial infarction (MI)/unstable angina within 6 mths prior to study
             enrollment

          -  History of stroke/transient ischemic attack within 6 mths prior to study enrollment

          -  Significant vascular disease

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by either:

          -  urine protein:creatinine (UPC) ratio >1.0 at screening /

          -  Urine dipstick for proteinuria ≥ 2+

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnant or lactating. Use of effective means of contraception in subjects of
             child-bearing potential