Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma
Condition: Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma
MeSH terms: Glioma; Astrocytoma; Ependymoma; Oligodendroglioma; Recurrence
Intervention: Diagnostic Laboratory Biomarker Analysis; Pharmacological Study; Sunitinib Malate
Intervention description: Correlative studies; Correlative studies; Given PO
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well sunitinib malate works in treating younger patients with
      recurrent, refractory, or progressive malignant glioma or ependymoma. Sunitinib malate may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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