PRIMARY OBJECTIVES:

      I. To determine the event-free survival (EFS) and overall survival (OS) of children with
      completely resected ependymoma treated with maintenance chemotherapy comprising vincristine
      sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following
      post-operative conformal radiotherapy (cRT).

      SECONDARY OBJECTIVES:

      I. To estimate the EFS and OS of children with incompletely resected ependymoma who are
      unable to achieve a complete response (CR) by post-operative induction chemotherapy or by
      second surgery who are non-randomly assigned to cRT followed by VCEC.

      II. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who
      achieve a complete resection at first or second resection or children who achieve a CR to
      short-course induction chemotherapy following first surgery.

      III. To determine the neurologic, neuropsychological, and endocrine long-term sequelae of
      surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.

      IV. To determine biologic prognostic factors in childhood ependymoma by utilizing genomic
      profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays, and
      microarray gene expression profiling analysis on initial tumor samples and correlating this
      with clinical outcome.

      V. To evaluate prognostic immune-function gene expression in ependymomas. VI. To build upon
      the data derived from COG-ACNS0121 to develop genotypically based classification signatures
      and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS.

      VII. To evaluate telomere maintenance as a prognostic marker.

      OUTLINE: This is a multicenter study. Patients are stratified according to extent of
      resection at initial surgery (total vs near total resection), tumor histology, and tumor
      location (infratentorial primary tumor vs supratentorial anaplastic tumor). Patients are
      randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumor are assigned
      to arm II.

      All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and
      8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on
      days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2
      only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or
      unacceptable toxicity. Patients achieving stable disease, partial response, or locally
      progressive disease and who are deemed potentially resectable undergo surgery within 15 days
      after completion of induction chemotherapy.

      ARM I: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive
      vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours
      on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes
      on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients undergo conformal radiotherapy over 6-7 weeks. Some patients undergo blood
      and tissue sample collection before treatment and after surgery for gene expression
      microarray, genomic hybridization array, and other correlative studies.

      After completion of study therapy, patients are followed up every 4 months for 5 years.