Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.

      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.
    

Intervention name(s): filgrastim; amifostine trihydrate; cisplatin; cyclophosphamide; vincristine sulfate; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure; Radiation
Other intervention name(s): PBSCT
Intervention MeSH terms: Cyclophosphamide; Vincristine; Amifostine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood medulloblastoma