Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating 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 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 tumour 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 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)
  • Overall survival (OS)
Secondary Outcome:
  • 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
  • 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
  • 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
  • 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
  • Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiation therapy, and maintenance chemotherapy
  • Gene expression signatures and genomic alterations in pediatric ependymoma
  • Telomere maintenance
PRIMARY OBJECTIVE: I. To determine the event free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with post-operative conformal radiation therapy (cRT) and then randomized to receive or not receive four cycles of post radiation maintenance chemotherapy (vincristine, cisplatin, etoposide and cyclophosphamide [VCEC]). EXPLORATORY 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 will then be non-randomly assigned to cRT followed by four cycles of maintenance chemotherapy (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 evaluate whether the addition of maintenance chemotherapy post-radiation therapy contributes to neurobehavioral morbidity and reduced functional outcomes over time, compared to patients treated with radiation therapy followed by observation alone. IV. To examine differences in neurobehavioral outcomes and quality of life of children treated with proton beam radiation therapy compared to children treated with conventional radiation delivery techniques. 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 tumour samples and correlating these data with clinical outcome. Va. To explore prognostic molecular signatures and genomic alterations in ependymomas by building upon the data derived from ACNS0121 to correlate biomarkers listed above with World Health Organization (WHO) grade, location, extent of resection, treatment, EFS and OS. OUTLINE:

Patients are assigned to Arm I or randomized to Arms II or III. Arm I: Patients receive vincristine intravenously (IV) over 1 minute on days 1 and 8 of cycles 1 and 2, carboplatin IV over 15-60 minutes on day 1 of cycles 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of cycle 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of cycle 2 only. Cycle 1 continues for 3 weeks and cycle 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response are randomized to Arm II or III. 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. Patients with sub total resection are assigned to Arm II. Patients with gross total resection undergo observation. ARM II: Patients undergo conformal radiation therapy over 6-7 weeks. Patients then receive vincristine IV on days 1, 8, and 15 of cycles 1-3 only, etoposide IV over 60-120 minutes on days 1-3, cisplatin IV over 1-8 hours on day 1, and cyclophosphamide IV over 30-60 minutes on days 2-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients undergo conformal radiation therapy over 6-7 weeks and then undergo observation. After completion of study therapy, patients are followed up every 4 months for 5 years, and then annually thereafter.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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