Hypofractionated Intensity-Modulated Radiation Therapy With Temozolomide and Bevacizumab for Glioblastoma Multiforme

Exclusion Criteria

• •Life expectancy of less than 12 weeks
• •Prior treatment, including radiation therapy or chemotherapy, for GBM with the exception of surgery (Gliadel Wafers are allowed at the time of surgery)
• •Active malignancy, with the exception of superficial basal cell and/or superficial squamous (skin) cell, or carcinoma in situ of the cervix
• •Active infection requiring IV antibiotics
• •Pregnant or breast feeding
• •International normalized ratio (INR) \> 1.5 and activated partial thromboplastin time (aPTT) \> 1.5 × the upper limit of normal (ULN) (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted
• •Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.3 grade 2 CNS hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only) is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a Grade 1 event for the purpose of this study. )
• •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
• •Current New York Heart Association (NYHA) Grade II or greater congestive heart failure
• •History of myocardial infarction or unstable angina within 6 months prior to enrollment
• •History of stroke or transient ischemic attack within 6 months prior to enrollment
• •Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to enrollment
• •History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to enrollment
• •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 enrollment or anticipation of need for major surgical procedure during the course of the study
• •Core needle biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
• •History of abdominal fistula or gastrointestinal perforation within 6 months prior to enrollment
• •Serious, non-healing wound, active ulcer, or untreated bone fracture
• •Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0 at screening (Appendix A).
• •Known hypersensitivity to any component of bevacizumab