All potentially eligible patients will have had an MRI of the brain and spine and will have undergone an operation to remove the tumor and determine a pathological diagnosis (standard-of-care). Upon recovery, patients will undergo a physical exam, laboratory evaluation and organ function evaluation (standard-of-care). Based upon these results, patients will then be assigned to a treatment arm, Low Risk, Intermediate Risk, or High Risk, according to the following criteria:
Low Risk Arm: (1) High-grade glioma with no CNS metastasis.
Intermediate-Risk Arm: (1) Nodular desmoplastic medulloblastoma with less than gross total resection, but with no metastasis; (2) Any eligible histologic diagnosis other than desmoplastic medulloblastoma, with no evidence of CNS metastasis.
High-Risk Arm: (1) Any eligible histologic diagnosis with evidence of CNS metastasis; (2) Patients with extraneural metastasis are eligible for treatment on the high-risk arm.
All patients will receive 4 identical cycles of induction chemotherapy including high-dose (5 g/m2) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide. Patients enrolled on the high-risk arm will also receive low-dose vinblastine between induction cycles. Induction will be followed by risk-adapted consolidation therapy: low-risk patients will receive further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide; intermediate risk patients will receive focal radiotherapy (RT) to the tumor bed; high-risk patients will receive either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16). All study medications are FDA approved but are not approved for use in this study. These study medications are considered standard of care for the treatment of pediatric embryonal brain tumors, high-grade glioma, and choroid plexus carcinoma of ependymoma.
1. Newly diagnosed tumor of the CNS, to include patients with: Medulloblastoma, Supratentorial PNET, Pineoblastoma, Atypical Teratoid Rhabdoid Tumor (ATRT), Choroid Plexus Carcinoma, High-Grade Glioma, Ependymoma
2. Age < 3 years of age at time of diagnosis for all histological diagnosis. Medulloblastoma patients >= 3 and < 5years old at diagnosis who have nonmetastatic disease with no more than 1 cm2 of residual tumor are also eligible. (Medulloblastoma patients in the >= 3 and < 5years old age group with anaplastic or large cell histology or with MYC or MYCN amplification are excluded. Pathology from collaborating institutions must be centrally reviewed prior to enrollment for confirmation.)
3. No previous radiotherapy or chemotherapy other than corticosteroid therapy
4. Patients must begin treatment as outlined in the protocol within 31 days of definitive surgery
5. Patients with adequate organ function prior to study entry
6. Adequate performance status as defined by Lansky Score >= 30 (Except for Posterior Fossa Syndrome)