Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Rhabdoid Tumor
Intervention: filgrastim; cisplatin; cyclophosphamide; vincristine; autologous hematopoietic stem cell transplantation; radiation therapy
Intervention description: Given subcutaneously; Given IV; Given IV; Given IV; Patients undergo autologous stem cell transplantation; Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
Intervention MeSH terms: Cyclophosphamide; Vincristine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 416.0
Sex: All
Minimum age: 3 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; childhood atypical teratoid/rhabdoid tumor; untreated childhood pineoblastoma

Summary:

      Drugs used in chemotherapy, such as vincristine, cisplatin, and cyclophosphamide, 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 radiation therapy with
      chemotherapy may kill more tumor cells. Autologous stem cell transplant may be able to
      replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. It is
      not yet known which radiation therapy regimen combined with chemotherapy and donor stem cell
      transplant is more effective in treating medulloblastoma, supratentorial primitive
      neuroectodermal tumor, or atypical teratoid rhabdoid tumor.

      This phase III trial is studying two different regimens of radiation therapy when given
      together with chemotherapy and autologous stem cell transplant to see how well they work in
      treating patients with newly diagnosed medulloblastoma, supratentorial primitive
      neuroectodermal tumor, or atypical teratoid rhabdoid tumor.

      PRIMARY OBJECTIVE:

        -  To assess the relationship between ERBB2 protein expression in tumors and
           progression-free survival probability for patients with medulloblastoma.

        -  To estimate the frequency of mutations associated with SHH and WNT tumors (as defined by
           gene expression profiling) via targeted sequencing performed in an independent cohort of
           WNT and SHH tumors (also defined by gene expression profiling).
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed diagnosis of 1 of the following:

               -  Medulloblastoma

               -  Supratentorial primitive neuroectodermal tumor (PNET)

               -  PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma)

               -  Atypical teratoid rhabdoid tumor (ATRT)

          -  Definitive surgery for CNS tumor within the past 31 days

          -  Meets one of the following risk criteria:

               -  Average-risk disease

                    -  Localized disease with no overt evidence of invasion beyond the posterior
                       fossa (or supratentorial compartment for PNET or ATRT) by intraoperative
                       observations of the neurosurgeon AND postoperative CT scan or MRI

                    -  T4 disease eligible if all of the following are true:

                         -  Gross total resection determined by intraoperative observations of the
                            neurosurgeon AND postoperative CT scan or MRI

                         -  Residual tumor or imaging abnormality whose size is < 1.5 cm^2

                         -  No evidence of CNS or extraneural metastasis by MRI of the spine (with
                            and without contrast agent) or CT-based myelogram AND by cytologic
                            examination of the lumbar cerebral spinal fluid (CSF) 14-28 days after
                            surgery

                    -  Brain stem invasion allowed in the absence of residual tumor (tumor < 1.5
                       cm^2 by imaging)

               -  High-risk disease meeting one of the following criteria:

                    -  Metastatic disease within the neuraxis (i.e., evidence of subarachnoid
                       dissemination by imaging and/or cytologic examination of CSF)

                    -  Presence of residual disease > 1.5 cm^2 at the primary site after surgery

        PATIENT CHARACTERISTICS:

        Age

          -  3 to 21 at diagnosis

        Performance status

          -  Lansky 30-100% (< 10 years old)

          -  Karnofsky 30-100% (≥ 10 years old) (except for posterior fossa syndrome)

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Hemoglobin > 8 g/dL

          -  WBC > 2,000/mm^3

          -  Absolute neutrophil count > 500/mm^3

          -  Platelet count > 50,000/mm^3

        Hepatic

          -  ALT < 5 times normal

          -  Bilirubin < 3.0 mg/dL

        Renal

          -  Creatinine < 2.0 mg/dL OR

          -  Creatinine clearance > 70 mL/min

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  Not specified

        Chemotherapy

          -  No prior chemotherapy

        Endocrine therapy

          -  Prior corticosteroid therapy allowed

        Radiotherapy

          -  No prior radiotherapy

        Surgery

          -  See Disease Characteristics