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