Central Nervous System Nongerminomatous Germ Cell TumorPhase 2NCT04684368
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
A Phase 2 study testing Biospecimen Collection, Carboplatin and Etoposide in people with Central Nervous System Nongerminomatous Germ Cell Tumor and Choriocarcinoma, run by Children's Oncology Group at 170 sites in 4 countries.
Trial summary
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). Read more about this study
- Who is it for?
- Ages 3 to 29 years
- Conditions the study is for
- Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma
- What is being tested?
- Biospecimen Collection, Carboplatin and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 170 sitesin 4 countries
- Study dates
- 13 Jul 2021to 21 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be >= 3 years and < 30 years at the time of study enrollment
- Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded
- Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
- Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. Note: The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment)
- Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment)
- Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. Note: False positive cytology can occur within 10 days of surgery. If lumbar CSF for cytology is not performed prior to surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. Patients with negative CSF cytology from lumbar puncture obtained 1 to 10 days after surgery do not need cytology repeated
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- Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
- Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
- Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment)
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows (within 7 days prior to enrollment):
- Age: Maximum serum creatinine (mg/dL)
- 3 to < 6 years: 0.8 (male), 0.8 (female)
- 6 to < 10 years: 1 (male), 1 (female)
- 10 to < 13 years: 1.2 (male), 1.2 (female)
- 13 to < 16 years: 1.5 (male), 1.4 (female)
- >= 16 years: male (1.7), 1.4 (female)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
- Central nervous system function defined as:
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
- Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
- Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
- NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
- English-, Spanish-, or French- speaking
- Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
- No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
- Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
- Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
Who cannot join
- Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
- Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
- Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
- Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
- Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
- Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
- Lactating females who plan to breastfeed their infants
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Trial locations and contacts
170 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
170 sites in 4 countries
United States152 sites, 142 recruiting
- Recruiting
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Site Public Contact, 330-543-3193
Erin Wright
- Recruiting
Albany Medical Center
Albany, New York, 12208
Site Public Contact, 518-262-5513
Lauren R. Weintraub
- Recruiting
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Site Public Contact, 610-402-9543, Morgan_M.Horton@lvhn.org
Jacob A. Troutman
- Recruiting
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Site Public Contact, 907-212-6871, AKPAMC.OncologyResearchSupport@providence.org
Brenda J. Wittman
- Recruiting
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Site Public Contact, 800-865-1125
Andrea T. Franson
- Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org
Jason R. Fangusaro
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org
Holly B. Lindsay
- Recruiting
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org
Shannon M. Cohn
- Recruiting
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Site Public Contact, 410-601-9083
Jason M. Fixler
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Kenneth J. Cohen
- Recruiting
Eastern Maine Medical Center
Bangor, Maine, 04401
Site Public Contact, 207-973-4274
Daniel L. Callaway
- Suspended
Children's Hospital of Alabama
Birmingham, Alabama, 35233
- Recruiting
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Site Public Contact, 208-381-2774, eslinget@slhs.org
Martha M. Pacheco
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Site Public Contact, 877-726-5130
Laura Wiltsie
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Site Public Contact, 877-442-3324
Kee Kiat Yeo
- Recruiting
Maimonides Medical Center
Brooklyn, New York, 11219
Site Public Contact, 718-765-2500
Mahmut Y. Celiker
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Site Public Contact, 800-767-9355, askroswell@roswellpark.org
Clare J. Twist
- Recruiting
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Site Public Contact, 802-656-8990, rpo@uvm.edu
Jessica L. Heath
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
Jacqueline M. Kraveka
- Recruiting
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Site Public Contact, 800-804-9376
Joel A. Kaplan
- Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Brian C. Belyea
- Recruiting
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Site Public Contact, 773-880-4562
Alicia Lenzen
- Recruiting
University of Illinois
Chicago, Illinois, 60612
Site Public Contact, 312-355-3046
Dipti S. Dighe
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Wendy S. Darlington
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Site Public Contact, 513-636-2799, cancer@cchmc.org
Trent R. Hummel
- Recruiting
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Site Public Contact, 216-844-5437
Duncan S. Stearns
- Active, not recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
- Recruiting
University of Missouri Children's Hospital
Columbia, Missouri, 65212
Site Public Contact, 573-882-1960, snwq62@health.missouri.edu
Barbara A. Gruner
- Recruiting
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Stuart L. Cramer
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Site Public Contact, 614-722-6039, Melinda.Triplet@nationwidechildrens.org
Mark A. Ranalli
- Recruiting
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Site Public Contact, 361-694-5311, Crystal.DeLosSantos@dchstx.org
Nkechi I. Mba
- Recruiting
Medical City Dallas Hospital
Dallas, Texas, 75230
Site Public Contact, 972-566-5588
Maurizio L. Ghisoli
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Daniel C. Bowers, 214-648-3896, Daniel.Bowers@utsouthwestern.edu
Daniel C. Bowers
- Recruiting
Geisinger Medical Center
Danville, Pennsylvania, 17822
Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu
Jagadeesh Ramdas
- Recruiting
Dayton Children's Hospital
Dayton, Ohio, 45404
Site Public Contact, 800-228-4055
Jordan M. Wright
- Recruiting
Blank Children's Hospital
Des Moines, Iowa, 50309
Site Public Contact, 515-241-8912, samantha.mallory@unitypoint.org
Samantha L. Mallory
- Recruiting
Children's Hospital of Michigan
Detroit, Michigan, 48201
Site Public Contact, helpdesk@childrensoncologygroup.org
Stephanie A. Toll
- Recruiting
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Site Public Contact, 626-564-3455
Hung N. Tran
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Jessica M. Sun
- Active, not recruiting
Michigan State University
East Lansing, Michigan, 48823
- Recruiting
El Paso Children's Hospital
El Paso, Texas, 79905
Site Public Contact, 915-298-5444, ranjan.bista@ttuhsc.edu
Benjamin Carcamo
- Recruiting
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Site Public Contact, 701-323-5760, OncologyClinicalTrialsFargo@sanfordhealth.org
Samuel J. Milanovich
- Recruiting
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org
Emad K. Salman
- Recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104
Site Public Contact, 682-885-2103, CookChildrensResearch@cookchildrens.org
Sibo Zhao
- Recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Site Public Contact, 352-273-8010, cancer-center@ufl.edu
Brian Stover
- Recruiting
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
East Carolina University
Greenville, North Carolina, 27834
Site Public Contact, 252-744-1015, eubankss@ecu.edu
Andrea R. Whitfield
- Recruiting
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Aniket Saha
- Recruiting
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Aniket Saha
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Site Public Contact, 551-996-2897
Derek R. Hanson
- Recruiting
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Site Public Contact, 860-545-9981
Michael S. Isakoff
- Suspended
Oncology Las Vegas - Henderson
Henderson, Nevada, 89074
- Recruiting
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Site Public Contact, 717-531-6012
Lisa M. McGregor
- Recruiting
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Site Public Contact, 808-983-6090
Wade T. Kyono
- Recruiting
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Site Public Contact, 713-798-1354, burton@bcm.edu
Jack M. Su
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Najat C. Daw, 713-792-6315, ndaw@mdanderson.org
Najat C. Daw
- Recruiting
Riley Hospital for Children
Indianapolis, Indiana, 46202
Sandeep Batra, 317-944-8784, batras@iu.edu
Sandeep Batra
- Recruiting
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Site Public Contact, 800-237-1225
Andrew P. Groves
- Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Site Public Contact, 601-815-6700
Amanda Strobel
- Recruiting
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Site Public Contact, 816-302-6808, COGResearchGroup@cmh.edu
Keith J. August
- Recruiting
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Site Public Contact, 865-541-8266
Susan E. Spiller
- Suspended
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
- Recruiting
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Site Public Contact, 800-639-6918, cancer.research.nurse@dartmouth.edu
Angela Ricci
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
James T. Badgett
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Site Public Contact, 501-364-7373
Michael W. Bishop
- Recruiting
Loma Linda University Medical Center
Loma Linda, California, 92354
Site Public Contact, 909-558-4050
Albert Kheradpour
- Recruiting
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Site Public Contact, 562-933-5600
Jacqueline N. Casillas
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Site Public Contact, 323-361-4110
Tom B. Davidson
- Recruiting
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Site Public Contact, 800-398-3996, clinical.trials@kp.org
Hung N. Tran
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Site Public Contact, 310-423-2133, Cancer.trial.info@cshs.org
Fataneh (Fae) Majlessipour
- Recruiting
Norton Children's Hospital
Louisville, Kentucky, 40202
Site Public Contact, 502-629-5500, CancerResource@nortonhealthcare.org
Michael J. Ferguson
- Recruiting
Valley Children's Hospital
Madera, California, 93636
Site Public Contact, 559-353-3000, Research@valleychildrens.org
Ruetima Titapiwatanakun
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Nicholas J. Pytel
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Nicholas J. Pytel
- Suspended
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Site Public Contact, 708-226-4357
Eugene Suh
- Recruiting
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Site Public Contact, 888-226-4343, referralinfo@stjude.org
Aditi Bagchi
- Recruiting
Banner Children's at Desert
Mesa, Arizona, 85202
Site Public Contact, 480-412-3100
Joseph C. Torkildson
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Bradley Gampel
- Recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
Site Public Contact, 888-624-2778
Ziad A. Khatib
- Recruiting
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Site Public Contact, 612-813-5913, pauline.mitby@childrensmn.org
Michael K. Richards
- Recruiting
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Site Public Contact, 304-293-7374, cancertrialsinfo@hsc.wvu.edu
Ashley E. Meyer
- Recruiting
Morristown Medical Center
Morristown, New Jersey, 07960
Site Public Contact, 973-971-5900
Kathryn L. Laurie
- Recruiting
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Site Public Contact, 615-342-1919
Clinton M. Carroll
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Adam J. Esbenshade
- Recruiting
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Site Public Contact, 732-745-8600 ext. 6163, kcovert@saintpetersuh.com
Nibal A. Zaghloul
- Recruiting
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Site Public Contact, 732-235-8675
Nehal S. Parikh
- Recruiting
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Asher M. Marks
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Asher M. Marks
- Recruiting
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Site Public Contact, 718-470-3460
Mark P. Atlas
- Recruiting
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Site Public Contact, 504-842-8084, Elisemarie.curry@ochsner.org
Craig Lotterman
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Elizabeth A. Raetz
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Sameer Farouk Sait
- Recruiting
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Site Public Contact, 973-926-7230, Christine.Kosmides@rwjbh.org
Nehal S. Parikh
- Recruiting
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org
Melissa S. Mark
- Recruiting
Kaiser Permanente-Oakland
Oakland, California, 94611
Site Public Contact, 877-642-4691, Kpoct@kp.org
Aarati V. Rao
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Rene Y. McNall-Knapp
- Recruiting
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Site Public Contact, 402-955-3949
Jill C. Beck
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Site Public Contact, 402-559-6941, unmcrsa@unmc.edu
Jill C. Beck
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
Site Public Contact, 714-509-8646, oncresearch@choc.org
Elyssa M. Rubin
- Recruiting
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Site Public Contact, 321-841-5357, Jennifer.spinelli@orlandohealth.com
Zhongbo Hu
- Recruiting
Nemours Children's Hospital
Orlando, Florida, 32827
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Site Public Contact, 800-694-0012, ccto-office@stanford.edu
Jay Michael S. Balagtas
- Recruiting
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Site Public Contact, 973-754-2207, HallL@sjhmc.org
Alissa Kahn
- Recruiting
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Site Public Contact, helpdesk@childrensoncologygroup.org
Jeffrey H. Schwartz
- Suspended
Sacred Heart Hospital
Pensacola, Florida, 32504
- Recruiting
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Site Public Contact, 309-624-4945, ChildrensHospitalofIllinois@osfhealthcare.org
Prerna Kumar
- Recruiting
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Site Public Contact, 215-427-8991
Gregory E. Halligan
- Recruiting
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Site Public Contact, 602-546-0920
Michael R. Mangum
- Recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Site Public Contact, 412-692-8570, jean.tersak@chp.edu
James T. Felker
- Recruiting
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Site Public Contact, 503-413-2560
Jason M. Glover
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Neha J. Patel
- Recruiting
Rhode Island Hospital
Providence, Rhode Island, 02903
Site Public Contact, 401-444-1488
Bradley DeNardo
- Recruiting
Renown Regional Medical Center
Reno, Nevada, 89502
Site Public Contact, 775-982-5050, Renown-CRD@renown.org
Alan K. Ikeda
- Suspended
Cancer Care Specialists - Reno
Reno, Nevada, 89511
- Active, not recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
- Recruiting
Carilion Children's
Roanoke, Virginia, 24014
Site Public Contact, 540-266-6238, wpmccarty@carilionclinic.org
Erwood G. Edwards
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Joseph Z. Wilson
- Recruiting
University of Rochester
Rochester, New York, 14642
Site Public Contact, 585-275-5830
David N. Korones
- Recruiting
Corewell Health Children's
Royal Oak, Michigan, 48073
Site Public Contact, 248-551-7695
Marie V. Nelson
- Recruiting
Primary Children's Hospital
Salt Lake City, Utah, 84113
Site Public Contact, 801-585-5270
Priya Chan
- Recruiting
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Site Public Contact, 210-704-2894, bridget.medina@christushealth.org
Julie Voeller
- Recruiting
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com
Jose M. Esquilin
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Site Public Contact, 210-450-3800, phoresearchoffice@uthscsa.edu
Shafqat Shah
- Recruiting
Rady Children's Hospital - San Diego
San Diego, California, 92123
Site Public Contact, 858-966-5934
William D. Roberts
- Recruiting
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Site Public Contact, 877-827-3222, cancertrials@ucsf.edu
Alyssa T. Reddy
- Recruiting
Maine Children's Cancer Program
Scarborough, Maine, 04074
Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org
Stanley Chaleff
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Site Public Contact, 866-987-2000
Sarah E. Leary
- Recruiting
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Site Public Contact, 605-312-3320, OncologyClinicalTrialsSF@SanfordHealth.org
Kayelyn J. Wagner
- Recruiting
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Site Public Contact, 800-228-6618, HopeBeginsHere@providence.org
Judy L. Felgenhauer
- Recruiting
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Site Public Contact, 314-268-4000
William S. Ferguson
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Mohamed S. Abdelbaki
- Recruiting
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Site Public Contact, 314-251-7066
Robin D. Hanson
- Recruiting
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu
Stacie L. Stapleton
- Recruiting
Stony Brook University Medical Center
Stony Brook, New York, 11794
Site Public Contact, 800-862-2215
Laura E. Hogan
- Recruiting
ProMedica Flower Hospital
Sylvania, Ohio, 43560
Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org
Jamie L. Dargart
- Recruiting
State University of New York Upstate Medical University
Syracuse, New York, 13210
Site Public Contact, 315-464-5476
Melanie A. Comito
- Recruiting
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Site Public Contact, 253-403-1461, research@multicare.org
Robert G. Irwin
- Recruiting
Madigan Army Medical Center
Tacoma, Washington, 98431
Site Public Contact, 253-968-6144, melissa.a.forouhar.mil@health.mil
Melissa A. Forouhar
- Recruiting
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Site Public Contact, 813-357-0849, jennifer.manns@baycare.org
Don E. Eslin
- Recruiting
Scott and White Memorial Hospital
Temple, Texas, 76508
Site Public Contact, 254-724-5407
Nicholas W. McGregor
- Recruiting
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Alice Lee
- Recruiting
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Alice Lee
- Recruiting
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org
Jamie L. Dargart
- Recruiting
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
Site Public Contact, UACC-IIT@uacc.arizona.edu
Monica M. Davini
- Suspended
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
- Recruiting
New York Medical College
Valhalla, New York, 10595
Site Public Contact, 914-594-3794
Andrew J. Bellantoni
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org
Jeffrey S. Dome
- Recruiting
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Sarah Supples
Canada11 sites, 11 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Site Public Contact, 403-220-6898, research4kids@ucalgary.ca
Victor A. Lewis
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Site Public Contact, 780-407-8798, pedsoncologyresearch@ahs.ca
Sarah J. McKillop
- Recruiting
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Site Public Contact, 902-470-8520, Research@iwk.nshealth.ca
Chelsea Ash
- Recruiting
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Site Public Contact, 905-521-2100
Uma H. Athale
- Recruiting
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Site Public Contact, 514-412-4445, info@thechildren.com
Stephanie Mourad
- Recruiting
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Site Public Contact, 514-345-4931, yvan.samson@umontreal.ca
Monia Marzouki
- Recruiting
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Site Public Contact, 418-525-4444, rechclinique@crchudequebec.ulaval.ca
Bruno Michon
- Recruiting
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
Site Public Contact, 819-820-6480, crcinformation.chus@ssss.gouv.qc.ca
Stephanie Vairy
- Recruiting
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Site Public Contact, 416-813-7654, ask.CRS@sickkids.ca
Pak Yin Anthony Liu
- Recruiting
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
Site Public Contact, 604-875-2345 ext. 6477
Rebecca J. Deyell
- Recruiting
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Site Public Contact, 866-561-1026, ctu_web@cancercare.mb.ca
Stephanie M. Villeneuve
Australia6 sites, 6 recruiting
- Recruiting
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia, 5006
Site Public Contact, (08) 8161 7327, cywhs.oncsec@health.sa.gov.au
Maria L. Kirby
- Recruiting
Royal Children's Hospital
Parkville, Victoria, 3052
Site Public Contact, 61 3 9345 5656, Jordan.Hansford@rch.org.au
Martin A. Campbell
- Recruiting
Perth Children's Hospital
Perth, Western Australia, 6009
Site Public Contact, helpdesk@childrensoncologygroup.org
Michelle Ng
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
Site Public Contact, (02) 9382-1721
David S. Ziegler
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Site Public Contact, 61 7 3068 1111
Steven A. Foresto
- Recruiting
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Site Public Contact, 61-2-9845 1400
Bhavna Padhye
New Zealand1 site, 1 recruiting
- Recruiting
Christchurch Hospital
Christchurch, 8011
Site Public Contact, 03 364 0640
Andrew J. Dodgshun
About this study
Official title: A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, 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. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.
Read the detailed description
PRIMARY OBJECTIVES:
- To monitor outcome to ensure that children and young adults with localized central nervous system (CNS) non-germinomatous germ cell tumors (NGGCT) treated with induction chemotherapy followed by response evaluation and whole ventricular + spinal canal irradiation (WVSCI) will maintain the excellent 2-year progression free survival (PFS) rate as compared to ACNS0122 (NCT00047320).
II. To improve disease control by decreasing the number of spinal relapses for patients who achieve a complete response (CR) or partial response (PR) and receive WVSCI as compared to whole ventricular radiation on ACNS1123 (NCT01602666).
SECONDARY OBJECTIVES:
- To estimate the response rates to induction chemotherapy and WVSCI for localized NGGCT patients who achieve a CR/PR.
II. To estimate the PFS and overall survival (OS) for localized NGGCT patients who achieve a CR/PR and receive WVSCI.
III. To estimate the PFS and OS for patients with less than a CR/PR following Induction who subsequently receive high-dose chemotherapy with peripheral stem cell rescue (HDCSCR).
IV. To estimate the response rate for patients with less than a CR/PR following Induction who subsequently receive HDCSCR.
EXPLORATORY OBJECTIVES:
- To prospectively compare outcomes based on radiation modality, photon versus proton, including cognitive, social and behavioral functioning, auditory, and neuro-endocrine function.
II. To compare spinal column growth and cell counts following radiation as measured by height and weight, and complete blood count (CBC) values during and after radiation therapy, based on treatment modality (photon versus [vs.] proton therapy) and planned inclusion/exclusion of the vertebral body in patients < 13 years of age.
III. To compare local vs. central review recommendations for second-look surgery and document barriers for performing such surgeries as well as their clinical benefit in pediatric NGGCT.
IV. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults with localized CNS NGGCT with testing as per the Children's Oncology Group (COG) Standardized Neuropsychological and Behavioral Battery.
- To evaluate patterns of disease recurrence/failure with respect to radiation dose distribution.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 of cycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation [WVSCI] or high-dose chemotherapy with peripheral stem cell rescue [HDCSCR]) based on response to induction chemotherapy:
- Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR.
- Patients who achieve less than radiographic CR/PR with marker normalization proceed to second-look surgery (unless contraindicated). If second-look surgery reveals mature teratoma or non-viable tumor, proceed to WVSCI. If second-look surgery reveals viable tumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery are removed from protocol therapy but remain on study for follow-up.
- Patients who achieve less than radiographic CR/PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.
- Patients who achieve radiographic PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.
PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-look surgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
PLAN B (CONSOLIDATION THERAPY [HDCSCR]): Within 6-9 weeks of the end of induction chemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients also undergo magnetic resonance imaging (MRI), as well as collection of cerebral spinal fluid (CSF) and blood sample throughout the trial.
After completion of study treatment, patients are followed for up to 10 years.
- Conditions
- Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor
- Being tested
- Biospecimen Collection, Carboplatin, Etoposide, Filgrastim, Ifosfamide
- Medical subject headings
- Choriocarcinoma, Carcinoma, Embryonal, Teratoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of CSF and blood samples
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
FilgrastimBiological
Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi
Given subcutaneously (SC) or IV
IfosfamideDrug
Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
MesnaDrug
Also called 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna
Given IV or orally
PegfilgrastimBiological
Also called Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01
Given SC
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation
Undergo PBSC transplant
Questionnaire AdministrationOther
Ancillary studies
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo WVSCI radiation therapy
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo Craniospinal radiation therapy
Second-Look SurgeryProcedure or surgery
Also called Reoperation, Repeat Surgery, Second Look, Surgical Revision
Undergo second-look surgery if needed
ThiotepaDrug
Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Plan A (chemotherapy, WVSCI, second-look surgery if needed) | Experimental | See Outline in Detailed Description. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Procedure: Magnetic Resonance Imaging; Drug: Mesna; Biological: Pegfilgrastim; Other: Questionnaire Administration; Radiation: Radiation Therapy; Procedure: Second-Look Surgery |
| Plan B (chemotherapy, HDCSCR, second-look surgery if needed) | Experimental | See Outline in Detailed Description. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Procedure: Magnetic Resonance Imaging; Drug: Mesna; Biological: Pegfilgrastim; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Questionnaire Administration; Radiation: Radiation Therapy; Procedure: Second-Look Surgery; Drug: Thiotepa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure rate
Will be measured by the number of progressions or deaths within 2 years of enrollment for the cohort treated with whole ventricular + spinal canal irradiation (WVSCI). The final analysis will include an exact binomial confidence interval of the failure rate for each of the failure types (local, distant/spinal or both) without adjustment for multiplicity.
Measured: Within 2 years of enrollment
Spinal failure rate
Will be measured by the number of spinal relapses (spine alone or distant relapses including the spine) within 2 years of enrollment in patients treated with WVSCI. The final analysis will include an exact binomial confidence interval of spinal failure rate.
Measured: Within 2 years of enrollment
Secondary outcomes (5)
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery
Will be assessed in patients treated with induction chemotherapy. Will be estimated using an exact binomial approach and its confidence interval.
Measured: Approximately 6 to 9 months post-treatment initiation
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)
Will be assessed in patients treated with HDCSCR. Will be estimated using an exact binomial approach and its confidence interval.
Measured: Up to 2 years post-treatment initiation
Progression-free survival (PFS)
Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based PFS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the primary analyses.
Measured: From enrollment until disease progression or death from any cause for patients with events, and until final follow up for those who are event free at the time of analysis, assessed up to 10 years
Overall survival (OS)
Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based OS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the secondary analyses.
Measured: From enrollment until death from any cause for patients with events and until final follow up for those who are alive at the time of analysis, assessed up to 10 years
Patterns of disease recurrence/failure
Will be analyzed in an exploratory manner with respect to radiation dose distribution.
Measured: Up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start13 Jul 2021
- Primary completion21 Dec 2029 (estimated)
- Study completion21 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System Nongerminomatous Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Shannon M MacDonald, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684368
- Sponsor's protocol ID
- ACNS2021
- Other IDs
- NCI-2020-13175, ACNS2021, ACNS2021, U10CA180886
- Status last verified
- Sep 2026
- First submitted
- 15 Dec 2020
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor
- ClinicalTrials.gov ID
- NCT04684368
- Acronym / sponsor ID
- ACNS2021
- Conditions
- Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Jul 2021 (actual)
- Primary completion
- 21 Dec 2029 (estimated)
- Study completion
- 21 Dec 2029 (estimated)
- First posted
- 24 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, 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. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.
Detailed description
PRIMARY OBJECTIVES:
- To monitor outcome to ensure that children and young adults with localized central nervous system (CNS) non-germinomatous germ cell tumors (NGGCT) treated with induction chemotherapy followed by response evaluation and whole ventricular + spinal canal irradiation (WVSCI) will maintain the excellent 2-year progression free survival (PFS) rate as compared to ACNS0122 (NCT00047320).
II. To improve disease control by decreasing the number of spinal relapses for patients who achieve a complete response (CR) or partial response (PR) and receive WVSCI as compared to whole ventricular radiation on ACNS1123 (NCT01602666).
SECONDARY OBJECTIVES:
- To estimate the response rates to induction chemotherapy and WVSCI for localized NGGCT patients who achieve a CR/PR.
II. To estimate the PFS and overall survival (OS) for localized NGGCT patients who achieve a CR/PR and receive WVSCI.
III. To estimate the PFS and OS for patients with less than a CR/PR following Induction who subsequently receive high-dose chemotherapy with peripheral stem cell rescue (HDCSCR).
IV. To estimate the response rate for patients with less than a CR/PR following Induction who subsequently receive HDCSCR.
EXPLORATORY OBJECTIVES:
- To prospectively compare outcomes based on radiation modality, photon versus proton, including cognitive, social and behavioral functioning, auditory, and neuro-endocrine function.
II. To compare spinal column growth and cell counts following radiation as measured by height and weight, and complete blood count (CBC) values during and after radiation therapy, based on treatment modality (photon versus [vs.] proton therapy) and planned inclusion/exclusion of the vertebral body in patients < 13 years of age.
III. To compare local vs. central review recommendations for second-look surgery and document barriers for performing such surgeries as well as their clinical benefit in pediatric NGGCT.
IV. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults with localized CNS NGGCT with testing as per the Children's Oncology Group (COG) Standardized Neuropsychological and Behavioral Battery.
- To evaluate patterns of disease recurrence/failure with respect to radiation dose distribution.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 of cycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation [WVSCI] or high-dose chemotherapy with peripheral stem cell rescue [HDCSCR]) based on response to induction chemotherapy:
- Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR.
- Patients who achieve less than radiographic CR/PR with marker normalization proceed to second-look surgery (unless contraindicated). If second-look surgery reveals mature teratoma or non-viable tumor, proceed to WVSCI. If second-look surgery reveals viable tumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery are removed from protocol therapy but remain on study for follow-up.
- Patients who achieve less than radiographic CR/PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.
- Patients who achieve radiographic PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.
PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-look surgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
PLAN B (CONSOLIDATION THERAPY [HDCSCR]): Within 6-9 weeks of the end of induction chemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients also undergo magnetic resonance imaging (MRI), as well as collection of cerebral spinal fluid (CSF) and blood sample throughout the trial.
After completion of study treatment, patients are followed for up to 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plan A (chemotherapy, WVSCI, second-look surgery if needed) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Drug: Etoposide, Biological: Filgrastim, Drug: Ifosfamide, Procedure: Magnetic Resonance Imaging, Drug: Mesna, Biological: Pegfilgrastim, Other: Questionnaire Administration, Radiation: Radiation Therapy, Procedure: Second-Look SurgerySee Outline in Detailed Description. |
| Plan B (chemotherapy, HDCSCR, second-look surgery if needed) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Drug: Etoposide, Biological: Filgrastim, Drug: Ifosfamide, Procedure: Magnetic Resonance Imaging, Drug: Mesna, Biological: Pegfilgrastim, Procedure: Peripheral Blood Stem Cell Transplantation, Other: Questionnaire Administration, Radiation: Radiation Therapy, Procedure: Second-Look Surgery, Drug: ThiotepaSee Outline in Detailed Description. |
Who may qualify
- Ages
- 3 to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (32 listed)
- Patients must be >= 3 years and < 30 years at the time of study enrollment
- Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded
- Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
- Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. Note: The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment)
- Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment)
Key exclusion criteria (8 listed)
- Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
- Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
- Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
- Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
- Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo collection of CSF and blood samples | Procedure or surgery | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| FilgrastimAlso: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafiGiven subcutaneously (SC) or IV | Biological | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| IfosfamideAlso: Asta Z 4942, Asta Z-4942, Cyfos, HoloxanGiven IV | Drug | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| MesnaAlso: 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, FilesnaGiven IV or orally | Drug | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| PegfilgrastimAlso: Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01Given SC | Biological | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| Peripheral Blood Stem Cell TransplantationAlso: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell TransplantationUndergo PBSC transplant | Procedure or surgery | Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| Questionnaire AdministrationAncillary studies | Other | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo WVSCI radiation therapy | Radiation | Plan A (chemotherapy, WVSCI, second-look surgery if needed) |
| Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo Craniospinal radiation therapy | Radiation | Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| Second-Look SurgeryAlso: Reoperation, Repeat Surgery, Second Look, Surgical RevisionUndergo second-look surgery if needed | Procedure or surgery | Plan A (chemotherapy, WVSCI, second-look surgery if needed), Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
| ThiotepaAlso: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, OncotiotepaGiven IV | Drug | Plan B (chemotherapy, HDCSCR, second-look surgery if needed) |
Primary outcome
Failure rate
Time frame: Within 2 years of enrollment
Will be measured by the number of progressions or deaths within 2 years of enrollment for the cohort treated with whole ventricular + spinal canal irradiation (WVSCI). The final analysis will include an exact binomial confidence interval of the failure rate for each of the failure types (local, distant/spinal or both) without adjustment for multiplicity.
Spinal failure rate
Time frame: Within 2 years of enrollment
Will be measured by the number of spinal relapses (spine alone or distant relapses including the spine) within 2 years of enrollment in patients treated with WVSCI. The final analysis will include an exact binomial confidence interval of spinal failure rate.
5 secondary outcomes
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery
Time frame: Approximately 6 to 9 months post-treatment initiation
Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)
Time frame: Up to 2 years post-treatment initiation
Progression-free survival (PFS)
Time frame: From enrollment until disease progression or death from any cause for patients with events, and until final follow up for those who are event free at the time of analysis, assessed up to 10 years
Overall survival (OS)
Time frame: From enrollment until death from any cause for patients with events and until final follow up for those who are alive at the time of analysis, assessed up to 10 years
Patterns of disease recurrence/failure
Time frame: Up to 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Providence Alaska Medical Center
Anchorage, United States
Shannon M MacDonald principal investigator
Children's Oncology Group
170 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biospecimen Collection, Carboplatin and Etoposide in people with Central Nervous System Nongerminomatous Germ Cell Tumor and Choriocarcinoma, run by Children's Oncology Group at 170 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 170 sites in United States, Canada, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failure rate (time frame: Within 2 years of enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.