Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma

Inclusion Criteria:

   - Patients must be diagnosed with ependymoma or high-grade glioma (World Health
   Organization [WHO] grade III/IV):

      - Stratum A: recurrent/progressive/refractory malignant glioma (i.e., anaplastic
      astrocytoma, glioblastoma multiforme [including giant cell and gliosarcoma
      types], anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic
      ganglioglioma) within the brain with or without spinal cord disease

      - Stratum B: recurrent/progressive/refractory ependymoma (including ependymoma
      variants) within the brain with or without spinal cord disease

      - Patients with diffuse intrinsic pontine glioma are not eligible

   - A histological diagnosis from either the initial presentation or at the time of
   recurrence is required

   - Patients must have radiographically documented measurable disease in the brain,
   defined as at least one lesion that can be accurately measured in at least 2 planes

   - To document the degree of residual tumor, the following must be obtained:

      - All patients must have a brain MRI with and without gadolinium and a spine
      magnetic resonance imaging (MRI), if clinically indicated,with and without
      gadolinium, performed within 2 weeks prior to study enrollment

      - Patients with evidence of new central nervous system (CNS) hemorrhage of more
      than punctate size and/or more than 3 foci of punctate hemorrhage on baseline MRI
      obtained within 14 days prior to study enrollment are not eligible

   - Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 (use
   Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age)

      - Neurological deficits in patients must have been relatively stable for a minimum
      of 1 week prior to study enrollment; patients who are unable to walk because of
      paralysis, but who are up in a wheelchair, will be considered ambulatory for the
      purpose of assessing the performance score

   - Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

   - Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet
   transfusions within the 7-day period prior to enrollment)

   - Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)

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

      - 0.4 mg/dL (1 month to < 6 months of age)

      - 0.5 mg/dL (6 months to < 1 year of age)

      - 0.6 mg/dL (1 to < 2 years of age)

      - 0.8 mg/dL (2 to < 6 years of age)

      - 1.0 mg/dL (6 to < 10 years of age)

      - 1.2 mg/dL (10 to < 13 years of age)

      - 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

      - 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

   - Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

   - Serum glutamic oxaloacetic transaminase (SGOT/AST) and serum glutamic pyruvic
   transaminase (SGPT/ALT) ≤ 2.5 times ULN

   - Shortening fraction of ≥ 27% by echocardiogram OR ejection fraction of ≥ 50% by
   radionuclide angiogram

   - Corrected QT interval < 450 msec (males) or < 470 msec (females)

   - Prothrombin time (PT) / international normalized ratio (INR) ≤ 1.5 times ULN

   - Partial thromboplastin time (PTT) ≤ 1.5 times ULN

   - Patients must not have a history of cardiac disease including, but not limited to:

      - Uncontrolled hypertension within 12 months prior to enrollment; uncontrolled
      hypertension is defined as follows:

         - Patients aged ≤ 17 years: greater than 95th percentile systolic and
         diastolic blood pressure based on age and height which is not controlled by
         one anti-hypertensive medication

         - Patients aged > 17 years: systolic blood pressure ≥ 140 mm Hg and/or
         diastolic blood pressure ≥ 90 mm Hg which is not controlled by one
         anti-hypertensive medication

      - Ongoing cardiac dysrhythmias ≥ grade 2 or atrial fibrillation of any grade

      - Unstable angina, symptomatic congestive heart failure, or myocardial infarction

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

      - Commonly used non-enzyme-inducing anticonvulsants include: gabapentin,
      lamotrigine, levetiracetam, tiagabine, topiramate, valproic acid, and zonisamide

   - Patients must not have had a cerebrovascular accident or transient is chemic attack
   within 12 months prior to enrollment

   - Patients must not have had a pulmonary embolism or other significant thromboembolic
   event within 12 months prior to enrollment

   - Patients must not have had grade ≥ 3 hemorrhage within 4 weeks prior to enrollment

   - Patients must not have had any of the following diagnoses within 6 months prior to
   enrollment: peptic ulcer disease, inflammatory bowel disease, or diverticulitis

   - Patients with a diagnosis of abdomen fistula, gastrointestinal (GI) perforation, or
   intra-abdominal abscess within 6 months prior to enrollment are not eligible

   - Patients who have an uncontrolled infection are not eligible

   - Patients with hypothyroidism that has not been well-controlled by medications for at
   least 2 weeks prior to study entry are not eligible

   - Patients who have a personal history of genetic and/or congenital cardiac
   abnormalities are not eligible

   - Patients who have a history of allergic reactions to compounds of similar chemical or
   biological composition to sunitinib are not eligible

   - Patients who have any other condition that could result in an inability to swallow
   capsules/sprinkles or absorb oral sunitinib administered through a gastric tube are
   not eligible

   - Patients with body surface area < 0.55 m^2 or > 2.18 m^2 are not eligible

   - Female patients who are pregnant are not eligible

   - Lactating females are not eligible unless they have agreed not to breastfeed their
   infants

   - Female patients of childbearing potential are not eligible unless a negative pregnancy
   test result has been obtained within the past 4 weeks

   - Sexually active patients of reproductive potential are not eligible unless they have
   agreed to use an effective contraceptive method for the duration of their study
   participation

   - No concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel,
   warfarin, heparin, low molecular weight heparin, dipyridamole, or aspirin therapy > 81
   mg/day

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

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

   - At least 7 days since the completion of therapy with a biologic agent; for agents that
   have known adverse events occurring beyond 7 days after administration, this period
   must be extended beyond the time during which adverse events are known to occur

   - At least 3 half-lives must have elapsed since prior therapy that included a monoclonal
   antibody

   - At least 24 weeks must have elapsed if prior full-field RT

      - ≥ 2 weeks must have elapsed if prior local palliative RT (small port) or
      limited-field RT

      - ≥ 3 months must have elapsed since prior stem cell transplant (SCT) or rescue
      with total-body irradiation (TBI)

         - No evidence of active graft-vs-host disease

   - Patients who are receiving dexamethasone must be on a stable or decreasing dose for at
   least 7 days prior to enrollment

   - Patients must not have received potent cytochrome P450-3A4 (CY3A4) inhibitors and/or
   inducers within 7 days prior to study enrollment and potent inducers within 12 days
   prior to study enrollment and during study

   - At least 7 days must have elapsed since the completion of therapy with a hematopoietic
   growth factor

   - Patients who have previously received sunitinib or who have received other VEGF-,
   PDGFR-, or KIT-targeted therapy are not eligible

      - Patients who received bevacizumab as part of their prior therapy may enroll on
      study

   - Patients must not have received more than 2 prior chemotherapy and/or RT regimens; for
   example, 1 initial treatment course of chemotherapy and/or RT (counts as 1 treatment
   course) and at relapse may have received 1 treatment course of chemotherapy and/or RT
   (counts as 1 treatment course)

   - Patients who received prior therapy with known risk for cardiovascular complications
   (e.g., anthracycline therapy or prior RT that included the heart and/or craniospinal
   radiation) are not eligible

   - Patients receiving ongoing treatment with therapeutic doses (i.e., therapeutic INR
   levels) of coumarin derivatives or oral anti-vitamin K agents are not eligible

   - Patients receiving antiretroviral therapy for human immunodeficiency virus (HIV)
   disease are not eligible

   - Patients who are started on protocol therapy on a phase II study prior to study
   enrollment are considered ineligible

   - No other concurrent chemotherapy, investigational agents, or immunomodulating agents

   - No concurrent RT