OBJECTIVES:

Primary

• 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

• 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.
• 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.
• To determine the neurologic, neuropsychological, and endocrine long-term sequelae of surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.
• 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.
• To evaluate prognostic immune-function gene expression in ependymomas.
• 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.
• 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.