Clinical Trial: Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children <36 Months Old With Intensive Induction Chemotherapy With Methotr

Brief Summary: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine if treatment of pediatric patients with newly diagnosed supratentorial primitive neuroectodermal CNS tumors or high-risk medulloblastoma with intensive induction chemotherapy comprising vincristine, etoposide, cyclophosphamide, and cisplatin in combination with high-dose methotrexate and leucovorin calcium followed by consolidation chemotherapy comprising carboplatin and thiotepa and peripheral blood stem cell rescue results in a higher complete response rate then in patients treated with the same regimen without high-dose methotrexate and leucovorin calcium.

SECONDARY OBJECTIVES:

I. Determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs.

II. Compare event-free survival and patterns of failure in patients treated with these regimens.

III. Compare the acute, chronic, and late effects of these regimens, particularly in terms of tolerance to the same consolidation regimen after treatment with 2 different induction regimens, in these patients.

IV. Compare the gastrointestinal and nutritional toxicities of these regimens in these patients.

V. Compare the quality of life outcomes in patients treated with these regimens.

VI. Compare the neuropsychological effects of these regimens in these patients.

OUTLINE: This is a randomized,
Sponsor: Children's Oncology Group

Current Primary Outcome: Complete response (CR) rate [ Time Frame: From baseline to up to 4 years ]

The analysis of response will be based on a one-sided, two-sample test of proportions, with Type I error of 10%. Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transverse (T), and length (L) measurements.


Original Primary Outcome:

Current Secondary Outcome:

  • Time to treatment failure defined as disease progression or recurrence, death from any cause, or occurrence of a second malignant neoplasm [ Time Frame: From baseline to up to 5 years ]

    The analysis of event-free survival (EFS) will be based on a proportional hazards, non-mixture parametric cure model (PCM).

    Partial stratification will be accomplished by separately estimating the scale parameter of the Weibull kernel function within each of the patient arms.

  • Toxicity rates of acute, chronic, and late effects of the two intense regimens [ Time Frame: From the beginning of treatment to end of study, assessed up to 4 years ]
    Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Patients who have progression or recurrence of disease will be censored in these analyses. Differences in incidence for treatment regimens will be tested with the log-rank test for overall pattern.
  • Rates of gastrointestinal and nutritional toxicities [ Time Frame: In each course or treatment ]
    Rates of gastrointestinal and nutritional toxicities will be summarized using standard descriptive statistical methods. The two groups will be compared using a Chi-square test to detect a significant difference in complications between the two groups.
  • Quality of life and neuropsychological (NP) scores as assessed by the Children Oncology Group (COG) Standard Neuropsychological and Behavioral Battery [ Time Frame: From baseline to up to 4 years ]
    Parent-report questionnaires will be completed to gather information about the patient's function, specifically in terms of attention, memory, executive abilities, and behavioral/social/emotional adaptation. Long-term effects of treatment on neuropsychological and quality of life outcomes will be primarily descriptive. Correlational analyses will be conducted, with Pearson product moment correlations computed for continuous data and chi-square analyses conducted for discrete data.
  • Gene expression profiling by northern blotting or by gel electrophoresis [ Time Frame: At baseline ]
    The methods used by Golub and colleagues and Pomeroy and colleagues, as well as standard statistical techniques such as Cox regression analysis will be used in these analyses. Internal cross-validation procedures, such as the leave-one-out method, will be utilized in the training set to provide less-biased estimates of correct classification rates.


Original Secondary Outcome:

Information By: Children's Oncology Group

Dates:
Date Received: June 8, 2006
Date Started: August 2007
Date Completion:
Last Updated: February 14, 2017
Last Verified: February 2017