RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy and radiation therapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy or radiation therapy and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy with topotecan, cyclophosphamide, cisplatin, and vincristine plus radiation therapy and peripheral stem cell transplantation in treating children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor.

OBJECTIVES:

• Estimate the response rate to topotecan in children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumors who have measurable residual disease after surgery. (Topotecan window closed to accrual 9/10/2001)
• Determine the feasibility of four courses of high-dose chemotherapy (vincristine, cisplatin, and cyclophosphamide) with peripheral blood stem cell support after craniospinal irradiation (CSI) in these patients.
• Estimate the 5-year overall survival and progression-free survival in patients treated with risk-adapted CSI and high-dose chemotherapy.
• Compare changes in intellectual functioning in patients treated with reduced-dose vs standard-dose CSI.
• Estimate the incidence of ototoxicity associated with risk-adapted CSI and posterior fossa boost(s) given by 3-D conformal radiotherapy technique combined with amifostine and cisplatin.
• Evaluate the relationship between amifostine and WR1065 plasma systemic exposure and pharmacologic effect (e.g., toxicity and reduction in cisplatin-induced ototoxicity).

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups based on risk status.

• Group 1 (average-risk): Patients receive filgrastim (G-CSF) subcutaneously (SC) or IV daily until peripheral blood stem cells (PBSC) are harvested. PBSC are harvested when blood counts recover. Patients then receive craniospinal irradiation (CSI) 5 days a week for 6 weeks. Beginning 6 weeks after completion of CSI, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients receive amifostine IV over 1 minute a maximum of 5 minutes prior to cisplatin infusion and then 3 hours into cisplatin infusion. PBSC are reinfused on day 0. Patients receive G-CSF SC beginning on day 1 and continuing for a minimum of 7 days or until blood counts recover. Vincristine IV is administered on day 6. G-CSF is stopped 48 hours prior to beginning subsequent courses of chemotherapy. High-dose chemotherapy repeats every 4 weeks for 4 courses.
• Group 2 (high-risk): Patients receive topotecan IV over 4 hours on days 1-5 and G-CSF SC or IV beginning 24 hours after completion of the first course of topotecan and continuing until PBSC are harvested. Treatment repeats every 3 weeks for 2 courses. If an adequate number of PBSC are not harvested, the patient undergoes a second harvest of PBSC after the second course of topotecan. Patients then receive CSI, high-dose chemotherapy, amifostine, and PBSC support as in group 1. (Topotecan window closed to accrual 9/10/2001) Patients undergo neuropsychological testing prior to radiotherapy and chemotherapy and then at 1, 2, and 5 years.

Patients are followed at 1, 2, 4, 6, 9, 12, 15, 18, and 24 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study within 5 years.

• Biological: filgrastim
• Drug: amifostine trihydrate
• Drug: cisplatin
• Drug: cyclophosphamide
• Drug: vincristine sulfate
• Procedure: peripheral blood stem cell transplantation
• Radiation: radiation therapy

• Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar 1;26(7):1112-8.
• Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-20. Erratum in: Lancet Oncol. 2006 Oct;7(10):797.

DISEASE CHARACTERISTICS:

• Histologically proven medulloblastoma or supratentorial primitive neuroectodermal tumor

• Average-risk group:

  • Localized tumor with no overt evidence of invasion beyond the posterior fossa
  • Less than 1.5 cm2 residual tumor/imaging abnormality
  • No CNS or extraneural metastasis (confirmed by bone scan)
  • Brain stem invasion allowed if above criteria met

• High-risk group:

  • Metastatic disease within the neuraxis (subarachnoid dissemination) OR greater than 1.5 cm^2 residual disease at the primary site after surgery
• No bone involvement by bone scan
• Must begin study within 28 days of definitive surgery

PATIENT CHARACTERISTICS:

Age

• 3 to 20 at diagnosis

Performance status

• ECOG 0-3 (except patients with posterior fossa syndrome)

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 3,000/mm^3
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic

• Bilirubin less than 1.5 mg/dL
• SGPT less than 1.5 times normal

Renal

• Creatinine less than 1.2 mg/dL OR
• Creatinine clearance greater than 70 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior corticosteroids allowed

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics