This partially randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.
Name: 3-Dimensional Conformal Radiation Therapy
Name: Carboplatin
Name: Cisplatin
Name: Clinical Observation
Name: Cyclophosphamide
Name: Etoposide
Name: Laboratory Biomarker Analysis
Name: Vincristine
Description: Using Kaplan-Meier curves to estimate the observed EFS for the two randomization arms (post-radiation maintenance arm and post-radiation observation only arm). Log rank tests will be used to compare the observed EFS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups. If outcome data on ACNS0121 or this study suggest a difference or a different pattern in outcome between the 2 randomization strata, the primary analyses will be supplemented with log-rank tests performed separately in each stratum in order not to confound the overall conclusions of the study with respect to the effect of maintenance therapy.
Measure: Event-free survival (EFS) Time: From first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause, assessed up to 5 yearsDescription: Using Kaplan-Meier curves to estimate the observed OS for the two randomization arms (post-radiation Maintenance arm and post-radiation Observation only arm). Log rank tests will be used to compare the observed OS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups. If outcome data on ACNS0121 or this study suggest a difference or a different pattern in outcome between the 2 randomization strata, the primary analyses will be supplemented with log-rank tests performed separately in each stratum in order not to confound the overall conclusions of the study with respect to the effect of maintenance therapy.
Measure: Overall survival (OS) Time: From the time of randomization to death, assessed up to 5 yearsDescription: Kaplan-Meier curves will be used to estimate the EFS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
Measure: Event free survival (EFS) of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by post-operative induction chemotherapy or by second surgery Time: Up to 5 yearsDescription: Kaplan-Meier curves will be used to estimate the OS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
Measure: Overall survival (OS) of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by post-operative induction chemotherapy or by second surgery Time: Up to 5 yearsDescription: Estimated using Kaplan-Meier curves for patients with supratentorial classic disease that achieve complete resection or CR to induction chemotherapy and are assigned to observation only.
Measure: Event free survival (EFS) of children with supratentorial classic ependymoma who achieve complete resection at first or second surgery or children who achieve complete response (CR) after induction chemo assigned to observation Time: Up to 5 yearsDescription: Estimated using Kaplan-Meier curves for patients with supratentorial classic disease that achieve complete resection or CR to induction chemotherapy and are assigned to observation only.
Measure: Overall survival (OS) of children with supratentorial classic ependymoma who achieve complete resection at first or second surgery or children who achieve complete response (CR) after induction chemo assigned to observation Time: Up to 5 yearsDescription: Will be observed.
Measure: Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy Time: At 9, 30, and 60 months post diagnosisDescription: Will be observed.
Measure: Gene expression signatures and genomic alterations in pediatric ependymoma Time: At the time of first or second surgeryDescription: Descriptive statistics will be used to summarize the various telomere maintenance measures. Log rank tests and multivariate Cox proportional hazards models will be used to explore the association between a telomere maintenance measurement and EFS/OS, with potential adjustments for the effects of other possible prognostic factors. Reliability of human telomerase reverse transcriptase (hTERT) immunohistochemistry results versus telomeric repeat amplification protocol (TRAP) assay results will be calculated using the kappa statistic.
Measure: Telomere maintenance Time: Up to 5 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
V. To evaluate biologic prognostic factors in childhood ependymoma by studying molecular groups as defined by deoxyribonucleic acid (DNA) methylation profiling and immunohistochemistry, copy number variants to identify 1q gain in posterior fossa ependymomas, CDKN2A loss (homozygous deletion) in supratentorial ependymomas and specific genetic alterations such as RELA fusions, YAP1 fusions and the H3 K27M mutation on initial tumor samples and correlating these data with clinical outcome. --- K27M ---