Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
Condition: Brain Tumors; Central Nervous System Tumors; Neuroblastoma
MeSH terms: Neoplasms; Neuroblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in different
      ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses
      high-energy x-rays to damage tumor cells. Combining carboplatin and vincristine with
      radiation therapy followed by adjuvant chemotherapy may kill more tumor cells.

      PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy
      plus radiation therapy followed adjuvant chemotherapy in treating young patients who have
      newly diagnosed high-risk CNS embryonal tumors.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the feasible dose and duration of carboplatin combined with craniospinal and
           local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk
           CNS embryonal tumors (Phase I completed as of 11-25-03).

        -  Determine the feasibility of administering cyclophosphamide and vincristine with or
           without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these
           patients.

        -  Determine the overall and individual toxicity rates of this regimen in these patients.

        -  Determine the complete response rate in patients treated with this regimen.

        -  Obtain preliminary estimates of event-free survival of patients treated with this
           regimen.

        -  Determine the prognostic significance of enhancing tumor after completion of
           radiotherapy on event-free survival of these patients.

      OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of
      11-25-03.)

      Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks
      and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a
      week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days
      a week for 6 weeks.

      Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12
      patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)

      At 6 weeks after completion of radiotherapy, patients are assigned to arm II for
      adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)

        -  Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1
           hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or
           subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood
           counts recover.

        -  Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine IV
           on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on day
           3 and continuing for at least 10 days until blood counts recover.

      In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.

      Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months
      for 2 years, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.
    

Intervention name(s): filgrastim; carboplatin; cisplatin; cyclophosphamide; vincristine sulfate; adjuvant therapy; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given IV; 1.8 Gy/fx x 20fx=36Gy Craniospinal XRT*
Other intervention name(s): G-CSF; Neupogen; NSC-614629; Paraplatin; NSC-241240; Platinol-AQ; NSC-119875; Cytoxan; NSC-26271; Oncovin; NSC-67574; radiotherapy
Intervention MeSH terms: Cyclophosphamide; Cisplatin; Carboplatin; Vincristine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood medulloblastoma; localized unresectable neuroblastoma; regional neuroblastoma; stage 4S neuroblastoma