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

Phase 3

Active, not recruiting

Conditions: Clear Cell Ependymoma
Papillary Ependymoma
Anaplastic Ependymoma
Cellular Ependymoma
Ependymoma
Brain Ependymoma

Interventions: Radiation: 3-Dimensional Conformal Radiation Therapy
Drug: Carboplatin
Other: Clinical Observation
Drug: Cyclophosphamide
Drug: Cisplatin
Drug: Etoposide
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Drug: Mesna
Drug: Vincristine

Registration Number: NCT01096368

Lead Sponsor: Children's Oncology Group

Brief Summary: The primary aim of this randomized phase III trial was to study whether the addition of maintenance chemotherapy delivered after surgical resection and focal radiation would be better than surgery and focal radiation alone. The trial also studied if patients who received induction chemotherapy and then either achieved a complete response or went on to have a complete resection would also benefit from maintenance chemotherapy. Children ages 1-21 years with newly diagnosed intracranial ependymoma were included. There were 2 arms that were not randomized. One arm studied patients with Grade II tumors located in the supratentorial compartment that were completely resected. One arm studied patients with residual tumor and those patients all received maintenance chemotherapy after focal radiation. Chemotherapy drugs, 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 in combination with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

Detailed Description: 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: This is a multicenter study partially randomized phase III study. Patients are randomized or non-randomly treated according to tumor location and extent of surgical resection or post-surgery induction chemotherapy response.

Arm I: Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.

ARM II: Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

ARM III: Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

ARM IV: Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are non-randomly assigned to Arm II treatment.

After completion of study therapy, patients are followed up every 4 months for 5 years, and then annually thereafter.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 479

Inclusion Criteria

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

Exclusion Criteria

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (radiotherapy, chemotherapy)	3-Dimensional Conformal Radiation Therapy	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm I (chemotherapy, observation)	Filgrastim	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
ARM IV (radiotherapy, chemotherapy)	Laboratory Biomarker Analysis	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
Arm I (chemotherapy, observation)	Laboratory Biomarker Analysis	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
ARM IV (radiotherapy, chemotherapy)	3-Dimensional Conformal Radiation Therapy	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
Arm II (radiotherapy, chemotherapy)	Laboratory Biomarker Analysis	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm III (radiotherapy, observation)	Laboratory Biomarker Analysis	Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
ARM IV (radiotherapy, chemotherapy)	Filgrastim	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
Arm III (radiotherapy, observation)	3-Dimensional Conformal Radiation Therapy	Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm III (radiotherapy, observation)	Clinical Observation	Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm I (chemotherapy, observation)	Cyclophosphamide	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
Arm I (chemotherapy, observation)	Carboplatin	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
Arm I (chemotherapy, observation)	Etoposide	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
Arm I (chemotherapy, observation)	Mesna	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
Arm I (chemotherapy, observation)	Vincristine	Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of 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.
Arm II (radiotherapy, chemotherapy)	Cisplatin	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm II (radiotherapy, chemotherapy)	Etoposide	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm II (radiotherapy, chemotherapy)	Cyclophosphamide	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm II (radiotherapy, chemotherapy)	Mesna	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
Arm II (radiotherapy, chemotherapy)	Vincristine	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
ARM IV (radiotherapy, chemotherapy)	Cisplatin	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
ARM IV (radiotherapy, chemotherapy)	Cyclophosphamide	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
ARM IV (radiotherapy, chemotherapy)	Etoposide	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
ARM IV (radiotherapy, chemotherapy)	Mesna	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
ARM IV (radiotherapy, chemotherapy)	Vincristine	Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
Arm II (radiotherapy, chemotherapy)	Filgrastim	Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of 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. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

Primary Outcome Measures

Name	Time	Method
Event-free Survival (EFS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only	Up to 10 years after enrollment. 5-year estimates of EFS are presented	Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval.
Overall Survival (OS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only	Up to 10 years after enrollment. 5-year estimates of OS are presented.	Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (209): Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
University of Illinois
🇺🇸
Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Maine Children's Cancer Program
🇺🇸
Scarborough, Maine, United States
Columbia Regional
🇺🇸
Columbia, Missouri, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
The Children's Hospital at Westmead
🇦🇺
Westmead, New South Wales, Australia
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
Sydney Children's Hospital
🇦🇺
Randwick, New South Wales, Australia
Starship Children's Hospital
🇳🇿
Grafton, Auckland, New Zealand
Nicklaus Children's Hospital
🇺🇸
Miami, Florida, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸
Indianapolis, Indiana, United States
University Medical Center of Southern Nevada
🇺🇸
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸
Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸
Las Vegas, Nevada, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Augusta University Medical Center
🇺🇸
Augusta, Georgia, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Covenant Children's Hospital
🇺🇸
Lubbock, Texas, United States
West Virginia University Healthcare
🇺🇸
Morgantown, West Virginia, United States
John Hunter Children's Hospital
🇦🇺
Hunter Regional Mail Centre, New South Wales, Australia
Queensland Children's Hospital
🇦🇺
South Brisbane, Queensland, Australia
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Valley Children's Hospital
🇺🇸
Madera, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸
Oak Lawn, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸
Toledo, Ohio, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
UMC Cancer Center / UMC Health System
🇺🇸
Lubbock, Texas, United States
Scott and White Memorial Hospital
🇺🇸
Temple, Texas, United States
Inova Fairfax Hospital
🇺🇸
Falls Church, Virginia, United States
Naval Medical Center - Portsmouth
🇺🇸
Portsmouth, Virginia, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸
Tacoma, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Carilion Children's
🇺🇸
Roanoke, Virginia, United States
Madigan Army Medical Center
🇺🇸
Tacoma, Washington, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
The Children's Hospital at TriStar Centennial
🇺🇸
Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Sanford Broadway Medical Center
🇺🇸
Fargo, North Dakota, United States
Perth Children's Hospital
🇦🇺
Perth, Western Australia, Australia
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Broward Health Medical Center
🇺🇸
Fort Lauderdale, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Michigan State University Clinical Center
🇺🇸
East Lansing, Michigan, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Tufts Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Banner Children's at Desert
🇺🇸
Mesa, Arizona, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Saint Mary's Hospital
🇺🇸
West Palm Beach, Florida, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Saint Luke's Cancer Institute - Boise
🇺🇸
Boise, Idaho, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
West Virginia University Charleston Division
🇺🇸
Charleston, West Virginia, United States
Sunrise Hospital and Medical Center
🇺🇸
Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
University of Vermont and State Agricultural College
🇺🇸
Burlington, Vermont, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸
Paterson, New Jersey, United States
T C Thompson Children's Hospital
🇺🇸
Chattanooga, Tennessee, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
NYU Winthrop Hospital
🇺🇸
Mineola, New York, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
Janeway Child Health Centre
🇨🇦
Saint John's, Newfoundland and Labrador, Canada
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
Royal Children's Hospital
🇦🇺
Parkville, Victoria, Australia
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸
Green Bay, Wisconsin, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Royal Brisbane and Women's Hospital
🇦🇺
Herston, Queensland, Australia
Monash Medical Center-Clayton Campus
🇦🇺
Clayton, Victoria, Australia
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦
Quebec, Canada
Royal Children's Hospital-Brisbane
🇦🇺
Herston, Queensland, Australia
Children's Hospital
🇨🇦
London, Ontario, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦
Ottawa, Ontario, Canada
Women's and Children's Hospital-Adelaide
🇦🇺
North Adelaide, South Australia, Australia
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Christchurch Hospital
🇳🇿
Christchurch, New Zealand
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Walter Reed National Military Medical Center
🇺🇸
Bethesda, Maryland, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Nemours Children's Hospital
🇺🇸
Orlando, Florida, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Arnold Palmer Hospital for Children
🇺🇸
Orlando, Florida, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸
Orlando, Florida, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Children's Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
University of Wisconsin Carbone Cancer Center
🇺🇸
Madison, Wisconsin, United States
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts