for people ages 13 months to 20 years (full criteria)
at Oakland, California and other locations
study started
estimated completion



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.

Official Title

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


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 tumor 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 radiotherapy 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 radiotherapy 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.


Anaplastic Ependymoma, Brain Ependymoma, Cellular Ependymoma, Clear Cell Ependymoma, Ependymoma, Papillary Ependymoma, Cyclophosphamide, Cisplatin, Carboplatin, Etoposide, Vincristine, Etoposide phosphate, Podophyllotoxin, 3-Dimensional Conformal Radiation Therapy, Clinical Observation, Laboratory Biomarker Analysis, radiotherapy, chemotherapy


You can join if…

Open to people ages 13 months to 20 years

  • Patients must be newly diagnosed with histologically confirmed intracranial ependymoma; patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above
  • There is no minimum performance level; children with ependymoma may suffer neurologic sequelae as a result of their tumor or surgical measures taken to establish a diagnosis and resect the tumor; in the majority of cases, there is neurologic recovery; neurologic recovery is not likely to be impeded by protocol therapy
  • REGULATORY: All patients and/or their parents or legal guardians must sign a written informed consent
  • REGULATORY: All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

You CAN'T join if...

  • Patients with evidence of metastatic disease will be excluded; any evidence of non-contiguous spread beyond the primary site as determined by pre or post-operative magnetic resonance (MR) imaging of brain, pre or post-operative MR imaging of the spine, and post-operative cerebrospinal fluid (CSF) cytology obtained from the lumbar CSF space (the requirement for lumbar CSF examination may be waived if deemed to be medically contraindicated); CSF cytology from a ventriculostomy or permanent ventriculoperitoneal (VP) shunt that reveals the presence of tumor cells is indicative of metastatic disease
  • Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma are NOT eligible
  • No prior treatment other than surgical intervention and corticosteroids; patients are allowed to have had more than one attempt at resection prior to enrollment
  • Pregnant female patients are not eligible for this study
  • Post-menarchal females may not participate unless a pregnancy test with a negative result has been obtained
  • Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Lactating females may not participate unless they have agreed not to breastfeed a child while on this study


  • UCSF Benioff Children's Hospital Oakland
    Oakland California 94609 United States
  • UCSF Medical Center-Parnassus
    San Francisco California 94143 United States
  • UCSF Medical Center-Mission Bay
    San Francisco California 94158 United States
  • Kaiser Permanente-Oakland
    Oakland California 94611 United States
  • Valley Children's Hospital
    Madera California 93636 United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto California 94304 United States


in progress, not accepting new patients
Start Date
Completion Date
Children's Oncology Group
Phase 3 research study
Study Type
About 477 people participating
Last Updated