Clinical Trial: Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

Brief 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 Summary:

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.

  • Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors [ Time Frame: 2 years after tumor cell analysis in 122 participants ]
    The relationship between ERBB2 protein expression in tumors and progression-free survival was assessed in 122 participants with a diagnosis of medulloblastoma and with ERBB2 protein assessments. If the ERBB2 value was greater than zero, the ERBB2 was defined as positive for the participant. If the ERBB2 value was zero, the ERBB2 was defined as negative. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
  • Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group. [ Time Frame: 2 years after tumor cell analysis in 122 participants ]
    122 participants with a diagnosis of medulloblastoma were grouped by ERBB2 positive/negative assessment and risk group into 4 groups. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
  • Frequency of Mutations Associated With SHH and WNT Tumors [ Time Frame: within 3.5 years following completion of accrual ]

    To estimate the frequency of mutations associated with SHH and WNT tumors via targeted sequencing.

    This outcome was initially expected to be completed by Sept

    Original Primary Outcome:

    Current Secondary Outcome:

    • Reading Decoding Composite Scores in the Intervention and Standard of Care Groups [ Time Frame: Measurements will be made at time of randomization, at 3 months from initiation of treatment, and yearly thereafter for 10 years ]
      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.
    • Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa [ Time Frame: Annually for 6 years post irradiation ]
      To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
    • Mean RT Dose to Specified Target Tissue Volume by Rate and Pattern of Failure, e.g. Local Failure, Distant Failure, Etc. [ Time Frame: Once all patients have been followed for 2 years ]
      To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.


    Original Secondary Outcome:

    Information By: St. Jude Children's Research Hospital

    Dates:
    Date Received: June 10, 2004
    Date Started: August 2003
    Date Completion: January 2023
    Last Updated: March 31, 2017
    Last Verified: January 2017