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
Study type: Interventional
Phase: Phase 3

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).
    

Detailed description: 
      SECONDARY OBJECTIVES:

        -  To compare the effects of a computer-based training system specifically targeting
           language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation)
           with the current standard of care on reading decoding skills as measured by individual
           academic testing.

        -  To monitor for treatment failure in the posterior fossa of patients whose tumor bed
           receives a reduced volume of radiation.

        -  To correlate radiation dosimetry of target and normal tissues with rate and patterns of
           failure and longitudinal measures of audiometric, endocrine and cognitive effects.

      EXPLORATORY OBJECTIVES:

        -  To estimate the change in neuropsychological performance from the neuropsychology
           assessment battery (intellect, academic achievement and cognitive ability) and examine
           the relationship of these changes to risk group, age at diagnosis, and parent measures.

        -  To evaluate the differences between neurotoxicity in the average-risk patient group with
           that in the high-risk group through qMRI, and fMRI.

        -  To develop or refine novel models relating impact of medulloblastoma therapy on
           neurocognitive performance to quantitative and functional neuroimaging measures.

      OUTLINE: This is a multicenter study. Patients are stratified according to disease risk
      (high-risk disease vs average-risk disease).

      Patients in both strata undergo peripheral blood stem cell or bone marrow harvest.

        -  Stratum 1 (high-risk group):

             -  Radiotherapy: Patients undergo craniospinal radiotherapy once daily 5 days a week
                for 6 weeks.

             -  High-dose chemotherapy and autologous stem cell transplantation (SCT): Six weeks
                after the completion of radiotherapy, 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 undergo autologous SCT
                on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and
                continuing until blood counts recover. Patients receive vincristine IV on day 6.
                High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional
                courses in the absence of unacceptable toxicity.

        -  Stratum 2 (average-risk group):

             -  Radiotherapy: Patients undergo craniospinal radiotherapy as in stratum 1, but at a
                lower dose.

             -  High-dose chemotherapy and autologous SCT: Patients receive high-dose chemotherapy,
                autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.

      Some patients undergo a neuropsychology assessment at baseline, before chemotherapy, and then
      annually for 5 years.

      After completion of study therapy, patients are followed every 3 months until month 30 (2.5
      years) after diagnosis and then every 6 months until month 72 (6 years) after diagnosis.
    

Intervention name(s): filgrastim; cisplatin; cyclophosphamide; vincristine; autologous hematopoietic stem cell transplantation; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): 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.
Other intervention name(s): Neupogen(R); G-CSF; Platinol-AQ(R); Cytoxan(R); Oncovin(R); autologous HSCT; RT; Craniospinal radiotherapy
Intervention MeSH terms: Cyclophosphamide; Vincristine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; childhood atypical teratoid/rhabdoid tumor; untreated childhood pineoblastoma