Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

Inclusion Criteria

• •Histologically confirmed high-grade glioma (WHO grade III or IV) at any site within the brain, including the following:
• •* Anaplastic astrocytoma
• •* Glioblastoma multiforme (including giant cell and gliosarcoma subtypes)
• •* Anaplastic oligodendroglioma
• •* Anaplastic ganglioglioma
• •* Anaplastic oligoastrocytoma
• •* Diffuse brain stem glioma
• •* Histologic confirmation not required
• •* Histologically confirmed medulloblastoma
• •* Histologically confirmed ependymoma
• •* Primary spinal cord malignant glioma with measurable metastatic disease within the brain
• •* Histologic confirmation required
• •* Neuraxis dissemination allowed provided there is bidimensionally measurable disease within the brain and spinal cord
• •* Low grade glioma at any site within the brain with or without spinal cord disease
• •Recurrent, progressive, or refractory disease (must have received prior chemoradiotherapy)
• •No more than 2 prior chemotherapy regimens following relapse
• •Bidimensionally measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 2 planes
• •If there is spinal cord disease as well, response assessment will be based only upon the measurable tumor in the brain
• •No diffuse gliomatosis cerebri with \< 1 discrete, measurable lesion
• •No evidence of new symptomatic CNS hemorrhage (\> grade 2) within the past 2 weeks
• •No central non-cerebellar PNET's (e.g., cerebral PNET or pineoblastoma)
• •No spinal cord tumors only
• •Karnofsky performance status (PS) 50-100% (\> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
• •Absolute neutrophil count ≥ 1,500/mm³ (unsupported)
• •Platelet count ≥ 100,000/mm³ (unsupported)
• •Hemoglobin \> 8 g/dL (support allowed)
• •Creatinine normal
• •BUN \< 25 mg/dL
• •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •ALT and AST ≤ 3 times ULN
• •Neurological deficits must be stable for ≥ 1 week prior to study entry
• •No active renal, cardiac (congestive cardiac failure, myocarditis), or pulmonary disease
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• •No clinically significant unrelated systemic illness that would preclude study treatment, including any of the following:
• •* Serious infections
• •* Significant cardiac, pulmonary, hepatic, or other organ dysfunction
• •* No uncontrolled systemic hypertension, defined as systolic blood pressure (BP) and/or diastolic BP \> 95th percentile for age
• •* No stroke, myocardial infarction, or unstable angina within the past 6 months
• •* No clinically significant peripheral vascular disease
• •* No significant traumatic injury within the past 6 weeks
• •* No evidence of bleeding diathesis, coagulopathy, or PT INR \> 1.5
• •* Urine protein/creatinine ratio ≤ 1.0
• •* No abdominal fistula or gastrointestinal perforation within the past 6 months
• •* No serious nonhealing wound, ulcer, or bone fracture
• •At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)
• •At least 7 days since prior investigational or biologic agents (3 weeks if patient experienced ≥ grade 2 myelosuppression or if agent has a prolonged half-life)
• •More than 7 days since prior minor surgery
• •More than 12 weeks since prior craniospinal or focal irradiation to primary tumor or other sites
• •At least 4 weeks since prior major surgery and recovered
• •At least 3 months since prior autologous bone marrow or stem cell transplantation
• •At least 2 weeks since prior colony-forming growth factors (i.e., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], epoetin alfa)
• •No prior bevacizumab or irinotecan hydrochloride
• •No anticipated surgery during treatment
• •No concurrent prophylactic G-CSF, GM-CSF, or epoetin alfa
• •Concurrent dexamethasone allowed provided the dose is stable or decreasing over the past week
• •No other concurrent anticancer or investigational drugs
• •No concurrent medications that may interfere with study (e.g., immunosuppressive agents other than corticosteroids)
• •No concurrent therapeutic anticoagulation
• •No concurrent nonsteroidal anti-inflammatory drugs, clopidogrel bisulfate, dipyridamole, or acetylsalicylic acid (aspirin) \> 81 mg/day