Phase II Study of Bi-Weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

Fecha de inicio: 1 de abril de 2009

Inclusion Criteria: Patients must have histologically confirmed diagnosis of a glioblastoma multiforme/gliosarcoma and: * Must have completed at least 2 cycles of adjuvant chemotherapy * Age \> 18 years * Karnofsky \> 60% * Hematocrit \> 29%, ANC \> 1,500 cells/dl, platelets \> 125,000 cells/dl * Serum creatinine \< 1.5 mg/dl, BUN \< 25 mg/dl, serum SGOT and bilirubin \< 1.5 times upper limit of normal * If on corticosteroids, must be on a stable dose for 1 week prior to entry; if clinically possible, the dose should not be escalated over entry dose level * Signed informed consent approved by the Institutional Review Board prior to study entry * If sexually active, will take contraceptive measures for the duration of the treatments Exclusion Criteria: * Prior toxicity grade ≥ 3 with TMZ * Prior treatment with bevacizumab * Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control * Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study * Acute or chronic liver disease (i.e., hepatitis, cirrhosis) * Confirmed diagnosis of HIV infection * Have received investigational drugs less than 4 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy * Have received chemotherapy within 2 weeks prior (6 weeks for nitrosourea) to entry on this study, or who have not recovered from the toxic effects of such therapy * Have received biologic, immunotherapeutic or cytostatic agents within 1 week prior to entry on this study or who have not recovered from the toxic effects of such therapy * Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant * Have received radiation therapy within 2 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy. * Surgical resection of brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy * Have had any surgery other than resection of a brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy * Unwilling to or unable to comply with the protocol * Evidence of tumor progression within on immediate post radiation brain imaging * Have not received at least 2 cycles of adjuvant chemotherapy * Life expectancy of less than 12 weeks * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study Bevacizumab-Specific Exclusions: * Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) * History of myocardial infarction or unstable angina within 6 months * History of stroke or transient ischemic attack within 6 months * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 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 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture. * Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening * Known hypersensitivity to any component of bevacizumab