Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma

Official Title

Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years

Summary:

This 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 tumour cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumour cells. Radiation therapy uses high-energy x-rays to kill tumour cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumour may kill more tumour cells and cause less damage to normal tissue. Giving chemotherapy with radiation therapy may kill more tumour cells and allow doctors to save the part of the body where the cancer started.

Trial Description

Primary Outcome:

  • Event-free survival (EFS) defined as time to the first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause
  • Overall survival (OS)
Secondary Outcome:
  • EFS and 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
  • EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second surgery or children who achieve a CR after induction chemotherapy assigned to observation
  • Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiation therapy, and maintenance chemotherapy
  • Gene expression signatures and genomic alterations in pediatric ependymoma
PRIMARY OBJECTIVES:
I. To determine the event-free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with maintenance chemotherapy comprising vincristine sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following post-operative conformal radiation therapy (cRT). SECONDARY OBJECTIVES:
I. To estimate the EFS and 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 who are non-randomly assigned to cRT followed by VCEC. II. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short-course induction chemotherapy following first surgery. III. To determine the neurologic, neuropsychological, and endocrine long-term sequelae of surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121. IV. To determine biologic prognostic factors in childhood ependymoma by utilizing genomic profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays, and microarray gene expression profiling analysis on initial tumour samples and correlating this with clinical outcome. V. To evaluate prognostic immune-function gene expression in ependymomas. VI. To build upon the data derived from COG-ACNS0121 to develop genotypically based classification signatures and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS. VII. To evaluate telomere maintenance as a prognostic marker. OUTLINE:

This is a multicentre study. Patients are stratified according to extent of resection at initial surgery (total vs near total resection), tumour histology, and tumour location (infratentorial primary tumour vs supratentorial anaplastic tumour). Patients are randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumour are assigned to arm II. All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2 only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, partial response, or locally progressive disease and who are deemed potentially resectable undergo surgery within 15 days after completion of induction chemotherapy. ARM I: Patients undergo conformal radiation therapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo conformal radiation therapy over 6-7 weeks. Some patients undergo blood and tissue sample collection before treatment and after surgery for gene expression microarray, genomic hybridization array, and other correlative studies. After completion of study therapy, patients are followed up every 4 months for 5 years.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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