- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01096368
Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Hunter Regional Mail Centre, New South Wales, Australia, 2310
- John Hunter Children's Hospital
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Randwick, New South Wales, Australia, 2031
- Sydney Children's Hospital
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Westmead, New South Wales, Australia, 2145
- The Children's Hospital at Westmead
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Queensland
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Herston, Queensland, Australia, 4029
- Royal Brisbane and Women's Hospital
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Herston, Queensland, Australia, 4029
- Royal Children's Hospital-Brisbane
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South Brisbane, Queensland, Australia, 4101
- Queensland Children's Hospital
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South Australia
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North Adelaide, South Australia, Australia, 5006
- Women's and Children's Hospital-Adelaide
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Medical Center-Clayton Campus
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Parkville, Victoria, Australia, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, Australia, 6008
- Princess Margaret Hospital for Children
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Perth, Western Australia, Australia, 6009
- Perth Children's Hospital
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Quebec, Canada, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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Alberta
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Calgary, Alberta, Canada, T3B 6A8
- Alberta Children's Hospital
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta Hospital
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- British Columbia Children's Hospital
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
- CancerCare Manitoba
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Newfoundland and Labrador
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Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
- Janeway Child Health Centre
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3K 6R8
- IWK Health Centre
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Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
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Kingston, Ontario, Canada, K7L 2V7
- Kingston Health Sciences Centre
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London, Ontario, Canada, N6A 5W9
- Children's Hospital
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Ottawa, Ontario, Canada, K1H 8L1
- Children's Hospital of Eastern Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3H 1P3
- The Montreal Children's Hospital of the MUHC
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Montreal, Quebec, Canada, H3T 1C5
- Centre Hospitalier Universitaire Sainte-Justine
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7N 4H4
- Saskatoon Cancer Centre
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Christchurch, New Zealand, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, New Zealand, 1145
- Starship Children's Hospital
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Alabama
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Birmingham, Alabama, United States, 35233
- University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, United States, 35233
- Children's Hospital of Alabama
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Arizona
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Mesa, Arizona, United States, 85202
- Banner Children's at Desert
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Phoenix, Arizona, United States, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, United States, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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Little Rock, Arkansas, United States, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, United States, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, United States, 91010
- City of Hope Comprehensive Cancer Center
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Loma Linda, California, United States, 92354
- Loma Linda University Medical Center
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Long Beach, California, United States, 90806
- Miller Children's and Women's Hospital Long Beach
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Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, United States, 90048
- Cedars Sinai Medical Center
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Madera, California, United States, 93636
- Valley Children's Hospital
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Oakland, California, United States, 94609
- UCSF Benioff Children's Hospital Oakland
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Oakland, California, United States, 94611
- Kaiser Permanente-Oakland
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Orange, California, United States, 92868
- Children's Hospital of Orange County
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Palo Alto, California, United States, 94304
- Lucile Packard Children's Hospital Stanford University
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Sacramento, California, United States, 95816
- Sutter Medical Center Sacramento
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Sacramento, California, United States, 95817
- University of California Davis Comprehensive Cancer Center
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San Diego, California, United States, 92123
- Rady Children's Hospital - San Diego
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San Francisco, California, United States, 94158
- UCSF Medical Center-Mission Bay
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San Francisco, California, United States, 94143
- UCSF Medical Center-Parnassus
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Colorado
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Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Medical Center
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New Haven, Connecticut, United States, 06520
- Yale University
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Delaware
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Wilmington, Delaware, United States, 19803
- Alfred I duPont Hospital for Children
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Washington, District of Columbia, United States, 20007
- MedStar Georgetown University Hospital
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Florida
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Fort Lauderdale, Florida, United States, 33316
- Broward Health Medical Center
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Fort Myers, Florida, United States, 33908
- Golisano Children's Hospital of Southwest Florida
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Fort Myers, Florida, United States, 33901
- Lee Memorial Health System
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Gainesville, Florida, United States, 32610
- University of Florida Health Science Center - Gainesville
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Hollywood, Florida, United States, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
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Jacksonville, Florida, United States, 32207
- Nemours Children's Clinic-Jacksonville
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Miami, Florida, United States, 33155
- Nicklaus Children's Hospital
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Miami, Florida, United States, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Orlando, Florida, United States, 32806
- Orlando Health Cancer Institute
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Orlando, Florida, United States, 32806
- Nemours Children's Clinic - Orlando
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Orlando, Florida, United States, 32827
- Nemours Children's Hospital
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Orlando, Florida, United States, 32803
- AdventHealth Orlando
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Orlando, Florida, United States, 32806
- Arnold Palmer Hospital for Children
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Pensacola, Florida, United States, 32504
- Nemours Children's Clinic - Pensacola
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Saint Petersburg, Florida, United States, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, United States, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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West Palm Beach, Florida, United States, 33407
- Saint Mary's Hospital
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Georgia
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Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta - Egleston
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Augusta, Georgia, United States, 30912
- Augusta University Medical Center
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Savannah, Georgia, United States, 31404
- Memorial Health University Medical Center
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Hawaii
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Honolulu, Hawaii, United States, 96826
- Kapiolani Medical Center for Women and Children
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Idaho
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Boise, Idaho, United States, 83712
- Saint Luke's Cancer Institute - Boise
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States, 60612
- University of Illinois
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Chicago, Illinois, United States, 60611
- Lurie Children's Hospital-Chicago
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Maywood, Illinois, United States, 60153
- Loyola University Medical Center
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Oak Lawn, Illinois, United States, 60453
- Advocate Children's Hospital-Oak Lawn
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Peoria, Illinois, United States, 61637
- Saint Jude Midwest Affiliate
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Springfield, Illinois, United States, 62702
- Southern Illinois University School of Medicine
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Indiana
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Indianapolis, Indiana, United States, 46202
- Riley Hospital for Children
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Indianapolis, Indiana, United States, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Des Moines, Iowa, United States, 50309
- Blank Children's Hospital
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Iowa City, Iowa, United States, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky/Markey Cancer Center
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Louisville, Kentucky, United States, 40202
- Norton Children's Hospital
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Ochsner Medical Center Jefferson
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New Orleans, Louisiana, United States, 70112
- Tulane University Health Sciences Center
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New Orleans, Louisiana, United States, 70118
- Children's Hospital New Orleans
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Maine
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Bangor, Maine, United States, 04401
- Eastern Maine Medical Center
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Scarborough, Maine, United States, 04074
- Maine Children's Cancer Program
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, United States, 21201
- University of Maryland/Greenebaum Cancer Center
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Bethesda, Maryland, United States, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Cancer Center
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Boston, Massachusetts, United States, 02111
- Tufts Children's Hospital
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Springfield, Massachusetts, United States, 01199
- Baystate Medical Center
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Michigan
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Ann Arbor, Michigan, United States, 48109
- C S Mott Children's Hospital
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Detroit, Michigan, United States, 48236
- Ascension Saint John Hospital
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East Lansing, Michigan, United States, 48824
- Michigan State University Clinical Center
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Flint, Michigan, United States, 48503
- Hurley Medical Center
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Grand Rapids, Michigan, United States, 49503
- Helen DeVos Children's Hospital at Spectrum Health
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Kalamazoo, Michigan, United States, 49007
- Bronson Methodist Hospital
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Minnesota
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Minneapolis, Minnesota, United States, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota/Masonic Cancer Center
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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Mississippi
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Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
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Missouri
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Columbia, Missouri, United States, 65201
- Columbia Regional
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Kansas City, Missouri, United States, 64108
- Children's Mercy Hospitals and Clinics
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, United States, 63141
- Mercy Hospital Saint Louis
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Saint Louis, Missouri, United States, 63104
- Cardinal Glennon Children's Medical Center
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Nebraska
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Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
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Omaha, Nebraska, United States, 68114
- Children's Hospital and Medical Center of Omaha
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Nevada
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Las Vegas, Nevada, United States, 89144
- Summerlin Hospital Medical Center
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Las Vegas, Nevada, United States, 89109
- Sunrise Hospital and Medical Center
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Las Vegas, Nevada, United States, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
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Las Vegas, Nevada, United States, 89102
- University Medical Center of Southern Nevada
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
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Livingston, New Jersey, United States, 07039
- Saint Barnabas Medical Center
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Morristown, New Jersey, United States, 07960
- Morristown Medical Center
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New Brunswick, New Jersey, United States, 08901
- Saint Peter's University Hospital
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New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
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Newark, New Jersey, United States, 07112
- Newark Beth Israel Medical Center
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Paterson, New Jersey, United States, 07503
- Saint Joseph's Regional Medical Center
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Summit, New Jersey, United States, 07902
- Overlook Hospital
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New Mexico
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Albuquerque, New Mexico, United States, 87102
- University of New Mexico Cancer Center
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New York
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Albany, New York, United States, 12208
- Albany Medical Center
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Bronx, New York, United States, 10467
- Montefiore Medical Center - Moses Campus
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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Mineola, New York, United States, 11501
- NYU Winthrop Hospital
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New Hyde Park, New York, United States, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, United States, 10029
- Mount Sinai Hospital
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New York, New York, United States, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New York, New York, United States, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Rochester, New York, United States, 14642
- University of Rochester
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Syracuse, New York, United States, 13210
- State University of New York Upstate Medical University
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Valhalla, New York, United States, 10595
- New York Medical College
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- UNC Lineberger Comprehensive Cancer Center
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Charlotte, North Carolina, United States, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Charlotte, North Carolina, United States, 28204
- Novant Health Presbyterian Medical Center
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, United States, 58122
- Sanford Broadway Medical Center
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Ohio
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Akron, Ohio, United States, 44308
- Children's Hospital Medical Center of Akron
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, United States, 44106
- Rainbow Babies and Childrens Hospital
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Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
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Dayton, Ohio, United States, 45404
- Dayton Children's Hospital
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Toledo, Ohio, United States, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
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Toledo, Ohio, United States, 43608
- Mercy Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, United States, 97227
- Legacy Emanuel Children's Hospital
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Pennsylvania
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Allentown, Pennsylvania, United States, 18103
- Lehigh Valley Hospital-Cedar Crest
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Bethlehem, Pennsylvania, United States, 18017
- Lehigh Valley Hospital - Muhlenberg
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Danville, Pennsylvania, United States, 17822
- Geisinger Medical Center
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Hershey, Pennsylvania, United States, 17033
- Penn State Children's Hospital
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States, 19134
- Saint Christopher's Hospital for Children
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Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
-
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Rhode Island
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Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
-
Columbia, South Carolina, United States, 29203
- Prisma Health Richland Hospital
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Greenville, South Carolina, United States, 29605
- BI-LO Charities Children's Cancer Center
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Greenville, South Carolina, United States, 29605
- Greenville Cancer Treatment Center
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South Dakota
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Sioux Falls, South Dakota, United States, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Tennessee
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Chattanooga, Tennessee, United States, 37403
- T C Thompson Children's Hospital
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Knoxville, Tennessee, United States, 37916
- East Tennessee Childrens Hospital
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Memphis, Tennessee, United States, 38105
- Saint Jude Children's Research Hospital
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Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
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Nashville, Tennessee, United States, 37203
- The Children's Hospital at TriStar Centennial
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Texas
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Austin, Texas, United States, 78723
- Dell Children's Medical Center of Central Texas
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Corpus Christi, Texas, United States, 78411
- Driscoll Children's Hospital
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Dallas, Texas, United States, 75230
- Medical City Dallas Hospital
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Fort Worth, Texas, United States, 76104
- Cook Children's Medical Center
-
Houston, Texas, United States, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
-
Lubbock, Texas, United States, 79410
- Covenant Children's Hospital
-
Lubbock, Texas, United States, 79415
- UMC Cancer Center / UMC Health System
-
San Antonio, Texas, United States, 78229
- University of Texas Health Science Center at San Antonio
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San Antonio, Texas, United States, 78207
- Children's Hospital of San Antonio
-
San Antonio, Texas, United States, 78229
- Methodist Children's Hospital of South Texas
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Temple, Texas, United States, 76508
- Scott and White Memorial Hospital
-
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Utah
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Salt Lake City, Utah, United States, 84113
- Primary Children's Hospital
-
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Vermont
-
Burlington, Vermont, United States, 05405
- University of Vermont and State Agricultural College
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Virginia
-
Falls Church, Virginia, United States, 22042
- Inova Fairfax Hospital
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Norfolk, Virginia, United States, 23507
- Children's Hospital of The King's Daughters
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Portsmouth, Virginia, United States, 23708-2197
- Naval Medical Center - Portsmouth
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
Roanoke, Virginia, United States, 24014
- Carilion Children's
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
-
Spokane, Washington, United States, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
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Tacoma, Washington, United States, 98405
- Mary Bridge Children's Hospital and Health Center
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Tacoma, Washington, United States, 98431
- Madigan Army Medical Center
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West Virginia
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Charleston, West Virginia, United States, 25304
- West Virginia University Charleston Division
-
Morgantown, West Virginia, United States, 26506
- West Virginia University Healthcare
-
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Wisconsin
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Green Bay, Wisconsin, United States, 54301
- Saint Vincent Hospital Cancer Center Green Bay
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center
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Marshfield, Wisconsin, United States, 54449
- Marshfield Medical Center-Marshfield
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Milwaukee, Wisconsin, United States, 53226
- Children's Hospital of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (chemotherapy, observation)
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC or IV
Other Names:
Given IV
Other Names:
Optional correlative studies
Given IV
Other Names:
|
Experimental: Arm II (radiotherapy, chemotherapy)
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.
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Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC or IV
Other Names:
Given IV
Other Names:
Optional correlative studies
Given IV
Other Names:
Patients undergo conformal radiotherapy
Other Names:
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Active Comparator: Arm III (radiotherapy, 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.
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Optional correlative studies
Patients undergo conformal radiotherapy
Other Names:
Patients undergo observation
Other Names:
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Active Comparator: ARM IV (radiotherapy, chemotherapy)
Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
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Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC or IV
Other Names:
Given IV
Other Names:
Optional correlative studies
Given IV
Other Names:
Patients undergo conformal radiotherapy
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented
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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.
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Up to 10 years after enrollment. 5-year estimates of EFS are presented
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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
Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented.
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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.
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Up to 10 years after enrollment. 5-year estimates of OS are presented.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 Frame: Up to 5 years
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Kaplan-Meier curves will be used to estimate the EFS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
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Up to 5 years
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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 Frame: Up to 5 years
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Kaplan-Meier curves will be used to estimate the OS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
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Up to 5 years
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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 Frame: Up to 5 years
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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.
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Up to 5 years
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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 Frame: Up to 5 years
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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.
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Up to 5 years
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Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy
Time Frame: At 9, 30, and 60 months post diagnosis
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Will be observed.
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At 9, 30, and 60 months post diagnosis
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Gene expression signatures and genomic alterations in pediatric ependymoma
Time Frame: At the time of first or second surgery
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Will be observed.
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At the time of first or second surgery
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Telomere maintenance
Time Frame: Up to 5 years
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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.
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Up to 5 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EFS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
Time Frame: 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) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
|
Up to 10 years after enrollment. 5-year estimates of EFS are presented.
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EFS With Incomplete Resection After Initial Surgery, Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
Time Frame: 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) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
|
Up to 10 years after enrollment. 5-year estimates of EFS are presented.
|
OS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only.
Time Frame: 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) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
|
Up to 10 years after enrollment. 5-year estimates of OS are presented.
|
OS in Children With Incomplete Resection After Initial Surgery Who Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
Time Frame: 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) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
|
Up to 10 years after enrollment. 5-year estimates of OS are presented.
|
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 and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy
Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented.
|
The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
|
Up to 10 years after enrollment. 5-year estimates of EFS are presented.
|
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 and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy
Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented.
|
The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause.
|
Up to 10 years after enrollment. 5-year estimates of OS are presented.
|
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 and Who Are Non-randomly Assigned to Observation
Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented.
|
The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
|
Up to 10 years after enrollment. 5-year estimates of EFS are presented.
|
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 and Who Are Non-randomly Assigned to Observation
Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented.
|
The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause.
|
Up to 10 years after enrollment. 5-year estimates of OS are presented.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Amy A Smith, Children's Oncology Group
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Ependymoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Adjuvants, Immunologic
- Keratolytic Agents
- Cyclophosphamide
- Carboplatin
- Etoposide
- Etoposide phosphate
- Cisplatin
- Podophyllotoxin
- Lenograstim
- Vincristine
- Mesna
Other Study ID Numbers
- ACNS0831 (Other Identifier: CTEP)
- U10CA180886 (U.S. NIH Grant/Contract)
- U10CA098543 (U.S. NIH Grant/Contract)
- NCI-2011-02029 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 10-01676
- COG-ACNS0831
- CDR0000668560
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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