Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma
Condition: Brain Tumors; Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Radiation therapy uses high energy x-rays to damage tumor cells. Drugs used in
      chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
      die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet
      known which chemotherapy regimen is more effective when combined with radiation therapy for
      treating medulloblastoma.

      PURPOSE: Randomized phase III trial to compare two combination chemotherapy treatments plus
      radiation therapy in treating children with newly diagnosed medulloblastoma.
    

Detailed description: 
      OBJECTIVES: I. Assess whether a cyclophosphamide-containing combination chemotherapy regimen
      increases progression-free survival compared to a lomustine-containing regimen in children
      with newly diagnosed, average-risk medulloblastoma. II. Determine progression-free and
      overall survival of children treated with craniospinal radiotherapy and local boost
      radiotherapy for a total dose of 5580 cGy followed by adjuvant
      lomustine/cisplatin/vincristine vs. cyclophosphamide/cisplatin/vincristine. III. Determine
      the long-term neurocognitive, endocrinologic, and cardiopulmonary sequelae associated with
      craniospinal radiotherapy, local boost radiotherapy, and adjuvant chemotherapy in these
      children, and determine whether replacement of lomustine with cyclophosphamide alters the
      incidence and degree of sequelae. IV. Determine whether cellular and biologic parameters,
      including tumor molecular genetic analysis, DNA ploidy, mitotic activity markers, and
      immunohistochemical analysis, are correlated with progression-free survival, overall
      survival, and patterns of disease relapse in these patients. V. Evaluate the utility of
      routine magnetic resonance imaging surveillance studies of the head and spine in detecting
      subclinical recurrent disease.

      OUTLINE: This is a randomized study. Patients are stratified by participating institution.
      Following surgery, patients are randomized to one of two groups. The first group receives
      craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week
      after initiation of radiotherapy, patients receive vincristine weekly for 8 doses. Beginning
      6 weeks after the completion of radiotherapy, patients receive adjuvant
      lomustine/vincristine/cisplatin every 6 weeks for a total of 8 courses. The second group
      receives craniospinal irradiation plus vincristine as above, followed by adjuvant
      cyclophosphamide/vincristine/cisplatin every 6 weeks for a total of 8 courses. Patients are
      followed every 3 months for 1 year, every 6 months for 2 years, then annually.

      PROJECTED ACCRUAL: It is anticipated that 240-300 patients will be entered over 4 years.
    

Intervention name(s): filgrastim; cisplatin; cyclophosphamide; lomustine; mesna; vincristine sulfate; low-LET electron therapy; low-LET photon therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Radiation; Radiation
Other intervention name(s): G-CSF; Neupogen; NSC-614629; Platinol; NSC-119875; Cytoxan; NSC-26271; CCNU; NSC-79037; Mesnex; NSC-113891; Oncovin; NSC-67574
Intervention MeSH terms: Cyclophosphamide; Lomustine; Cisplatin; Vincristine
Allocation: Randomized
Masking: Single
Primary purpose: Treatment
Keywords: untreated childhood medulloblastoma