The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors

Inclusion Criteria: * Age ≥ 1 and \< 25 years of age at diagnosis * Interval from radiation therapy at least 4 weeks and no more than 1 year * Neurologic deterioration (long tract signs, cranial nerve signs or ataxia) consistent with radiation necrosis * MRI imaging with findings consistent with radiation necrosis as confirmed by the study radiologist * Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry * More than 28 days elapsed from the last surgical procedure (including biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) * Lansky or Karnofsky performance \> 40% * Patients may be on steroids at study entry * Adequate organ function defined as: * Peripheral absolute neutrophil (ANC) \>/= 1000/units/Liter(uL) * Platelet count \>/= 50,000/uL * Hemoglobin \>/= 9.0 gm/dL (transfusion permitted) * Adequate Coagulation function defined as: * Prothrombin Time (PT)/activated Partial Thromboplastin Time (aPTT) \</= 1.5x institutional upper limit of normal (ULN) for age; * Adequate Renal Function defined as: * Serum creatinine \</= 1.5x institutional upper limit of normal (ULN) for age. If the serum creatinine is above these values, the calculated creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) must be \>/= 60 mL/min/1.73m2; * Adequate Hepatic Function defined as: * Total bilirubin \</= 1.5x institutional upper limit of normal (ULN); * Alanine Amniotransferase (ALT) and Aspartate Aminotransferase(AST) \</= 2.5x ULN for institution;Serum albumin \</= 2.0 g/dL; * QT corrected (QTc) interval within normal range for age; * Adequate Pulmonary Function defined as: * Room air oxygen saturation of \>90% at altitude \> 5000 feet, or \>93% \< 5000 feet * Chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy prior to entering study. Three (3) weeks must have elapsed since the administration of prior chemotherapy. * Biologic agents: At least 14 days must have elapsed since the completion of therapy with a monoclonal antibody * Stem cell transplant: patients who have undergone prior stem cell transplant will not be excluded from study entry as long as adequate marrow reserve is demonstrated (refer to hematologic parameters). * For females of childbearing potential, a negative serum pregnancy test must be documented prior to enrollment * Patients who enter this study and their sexual partners who are of childbearing potential must agree to use an effective form of contraception throughout participation in this study * Written informed consent and assent as required by institutional guidelines Exclusion Criteria: 1. Disease-Specific Exclusions •Evidence of recent (less than 2 weeks) hemorrhage on postoperative MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumour are permitted entry into the study. 2. General Medical Exclusions * Subjects meeting any of the following criteria are ineligible for study entry: * Inability to comply with study and/or follow-up procedures * Life expectancy of less than 12 weeks * Patients who have had chemotherapy within three (3) weeks or radiation within four (4) weeks. Patients may not receive additional chemotherapeutic agents while on this study. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Active second malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years. 3. Bevacizumab-Specific Exclusions * Inadequately controlled hypertension (defined as above the normal published range for age and height) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 12 months prior to Day 1 * No history of stroke or transient ischemic attack * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1; History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 * 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 prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or unhealed bone fracture * Proteinuria as demonstrated by a Urine Protein Creatinine (UPC) ratio greater than or equal to 1.0 at screening * Known hypersensitivity to any component of bevacizumab * Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential