Phase II Study of Bevacizumab Plus Irinotecan (Camptosar™) in Children With Recurrent, Progressive, or Refractory Malignant Gliomas, Diffuse/Intrinsic Brain Stem Gliomas, Medulloblastomas, Ependymomas and Low Grade Gliomas

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- 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

- No other concurrent anticancer or investigational drugs

- Concurrent dexamethasone allowed provided the dose is stable or decreasing over the
past week

- 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