Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Fecha de inicio: 1 de agosto de 2007

Inclusion Criteria: Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease. * Age ≥ 18years \& life expectancy of \>12 weeks * Evidence of measurable primary CNS neoplasm on contrast enhanced MRI. * Interval of \<1 week between prior biopsy/4 weeks from surgical resection \& enrollment on protocol * Karnofsky ≥60% * Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter * Serum creatinine ≤1.5 mg/dl, serum SGOT \& bilirubin ≤1.5 x ULN * For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, \& dose should not be escalated over entry dose level * Signed informed consent approved by IRB prior to patient entry * No evidence of \> grade 1 CNS hemorrhage on baseline MRI/CT scan * If sexually active, patients will take contraceptive measures for duration of treatments Exclusion Criteria: * Pregnancy/breast feeding * Co-medication that may interfere with study results * Active infection requiring IV antibiotics * Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor * Evidence of \> grade 1 CNS hemorrhage on baseline MRI or CT scan Avastin-Specific Concerns: * Inadequately controlled hypertension * Any prior history of hypertensive crisis/hypertensive encephalopathy * New York Heart Association Grade II or \> congestive heart failure * History of myocardial infarction/unstable angina \< 6 months prior to study enrollment * History of stroke/transient ischemic attack \< 6 months prior to study enrollment * Significant vascular disease * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis/coagulopathy * Major surgical procedure, open biopsy,/significant traumatic injury within 28 days prior to study enrollment/anticipation of need for major surgical procedure during course of study * Core biopsy/other minor surgical procedure, excluding placement of vascular access device, \<7 days prior to study enrollment * History of abdominal fistula, GI perforation, /intra-abdominal abscess \<6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening as demonstrated by either * UPC ratio ≥1.0 at screening OR * Urine dipstick for proteinuria ≥2+ * Known hypersensitivity to any component of Avastin * Pregnant/lactating. Use of effective means of contraception in subjects of child-bearing potential * Current, ongoing treatment with full-dose warfarin or its equivalent