Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors

Inclusion Criteria:

   - Medulloblastoma or PNET of childhood that has relapsed or become refractory to
   standard chemotherapy; patients with pineoblastoma are eligible

   - Patients must have had histologic verification of the malignancy at original diagnosis
   or at the time of recurrence

   - Patients must have clear residual disease, defined as tumor that is measurable in two
   perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal
   disease OR clear MRI evidence of disease that may not be measurable in two
   perpendicular diameters

   - All patients must have a brain MRI with and without gadolinium and a spine MRI with
   gadolinium performed within 2 weeks prior to study enrollment

   - Patients must have a Lansky or Karnofsky performance status score of >= 50%,
   corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2
   (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of
   age)

   - Patients must have a life expectancy of >= 8 weeks

   - Patients must have experienced at least one and at most two relapses prior to study
   enrollment; patients with primary refractory disease are eligible

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy prior to entering this study

      - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry
      onto this study (6 weeks if prior nitrosourea)

      - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
      with a biologic agent; at least 3 weeks for biologic agents with a long half
      life, such as antibodies

      - External beam radiation therapy (XRT): Must not have received craniospinal
      radiotherapy within 24 weeks prior to study entry; the tumor designated as
      "measurable" for protocol purposes must not have received radiation within 12
      weeks prior to study entry); focal radiation to areas of symptomatic metastatic
      disease must not be given within 14 days of study entry

      - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed
      prior to study entry

      - Study specific limitations on prior therapy:

         - Patients must not have previously received bevacizumab, irinotecan,
         temozolomide or other anti-vascular endothelial growth factor (VEGF)
         inhibitor

         - Patients must not be taking enzyme-inducing antiepileptic medicines within 1
         week of study entry

   - Patients must have recovered from any surgical procedure before enrolling on this
   study:

      - Patients with a major surgical procedure within 28 days prior to enrollment
      should be excluded

      - Patients with an intermediate surgical procedure within 14 days prior to
      enrollment should be excluded

      - For minor surgical procedures (including Broviac line or infusaport placement),
      patients should not receive the first planned dose of bevacizumab until the wound
      is healed and at least 7 days have elapsed

      - There should be no anticipation of need for major surgical procedures during the
      course of the study

         - Examples of major, intermediate, or minor surgical procedures:

            - Major procedures: Major craniotomy for tumor resection; organ
            resection; bowel wall anastomosis; arteriovenous grafts; exploratory
            laparotomy; thoracotomy

            - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement;
            stereotactic brain biopsy

            - Minor procedures: Incision and drainage of superficial skin abscesses;
            punch biopsy of skin lesions; superficial skin wound suturing; bone
            marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or
            infusaport placement; paracentesis or thoracocentesis

      - Please note: Lumbar punctures or placement of peripherally inserted central
      catheter (PICC) lines are not considered minor procedures and may occur at any
      time prior to or during therapy

   - Hypertension must be well controlled (=< 95th percentile for age and height if patient
   is =< 17 years) on stable doses of medication

   - Concomitant medications restrictions:

      - Growth factor(s): Must not have received within 7 days of entry onto this study

      - Steroids: Patients who are receiving corticosteroids must be on a stable or
      decreasing dose for at least 7 days

      - Study Specific: Patients must not be currently taking nonsteroidal
      anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy >
      81 mg/day

   - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received
   filgrastim [G-CSF] within the prior 7 days)

   - Platelet count >= 100,000/uL (transfusion independent)

   - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions)

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR
   a serum creatinine based on age/gender as follows:

      - =< 0.4 mg/dL (for patients aged 1 month to < 6 months)

      - =< 0.5 mg/dL (for patients aged 6 months to < 1 year)

      - =< 0.6 mg/dL (for patients aged 1 to < 2 years)

      - =< 0.8 mg/dL (for patients aged 2 to < 6 years)

      - =< 1 mg/dL (for patients aged 6 to < 10 years)

      - =< 1.2 mg/dL (for patients aged 10 to < 13 years)

      - =< 1.4 mg/dL (for female patients aged >= 13 years)

      - =< 1.5 mg/dL (for male patients aged 13 to < 16 years)

      - =< 1.7 mg/dL (for male patients aged >= 16 years)

   - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick,
   then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5,
   24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours
   for patient enrollment

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x
   upper limit of normal (ULN) for age

   - Central nervous system function defined as

      - Patients with a seizure disorder may be enrolled if well-controlled and on
      non-enzyme inducing anticonvulsants

   - Adequate coagulation defined as

      - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit
      of normal

Exclusion Criteria:

   - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible
   for this study

   - Patients must not have a history of abdominal fistula, gastrointestinal perforation or
   intra-abdominal abscess within 6 months prior to study entry

   - Patients must not have a known bleeding diathesis or coagulopathy

   - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring
   surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to
   study entry

   - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or
   antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation,
   homocysteinemia or antiphospholipid antibody syndrome); testing is not required in
   patients without thrombophilic history

   - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within
   14 days prior to study enrollment

   - Patients with a history of stroke, myocardial infarction, transient ischemic attack
   (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater
   congestive heart failure within the past 6 months are not eligible

   - Patients must not have serious and inadequately controlled cardiac arrhythmia

   - Female patients who are pregnant are not eligible for this study

   - Female patients who are breastfeeding are not eligible for this study unless they
   agree not to breastfeed

   - Female patients of childbearing potential must have a negative pregnancy test

   - Sexually active patients of childbearing potential must agree to use an effective
   method of contraception during the study and for at least 6 months after the
   completion of bevacizumab therapy

   - Patients with known hypersensitivity to Chinese hamster ovary cell products or other
   recombinant human antibodies