Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children < 36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue vs. the Same Therapy Without Methotrexate
7 other identifiers
interventional
91
4 countries
145
Brief Summary
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma when given before additional intense chemotherapy followed by peripheral blood stem cell rescue. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Oct 2007
Longer than P75 for phase_3
145 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2006
CompletedFirst Posted
Study publicly available on registry
June 12, 2006
CompletedStudy Start
First participant enrolled
October 22, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2016
CompletedResults Posted
Study results publicly available
October 24, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2025
CompletedJanuary 23, 2026
January 1, 2026
9.2 years
June 8, 2006
December 18, 2017
January 6, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate
At the end of consolidation, the number of evaluable patients treated with intensive chemotherapy with methotrexate who achieved CR or not will be compared to those who achieved CR or not after treated with the same intensive chemotherapy without methotrexate. The CR rates between these two groups will be compared at a significance level of 0.1 using one-sided Chi-square test. Complete Response (CR) requires: CR for target lesions: disappearance of all target lesions, CR for non-target lesions: disappearance of all non-target lesions and no new lesions. No CR is any response not fitting the definition of CR.
At the end of consolidation treatment
Secondary Outcomes (14)
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort
At baseline
Percentage of Participants With Event Free Survival (EFS)
Baseline to up to 5 years
Patterns of Failure
Baseline to up to 5 years
Percentage of Participants With Any Acute Adverse Events
Beginning of treatment to the end of consolidation
Number of Participants With Acute Hearing Loss and No Acute Hearing Loss
Beginning of treatment to the end of consolidation
- +9 more secondary outcomes
Study Arms (2)
Arm I (induction+consolidation chemotherapy, autologous PBSC)
ACTIVE COMPARATORPatients receive vincristine IV over 1 minute on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Arm II (induction+consolidation chemotherapy, autologous PBSC)
EXPERIMENTALPatients receive vincristine IV over 1 minute on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or PO every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo autologous PBSC resuce
Given IV
Given IV or SC
Correlative studies
Given IV or orally
Given IV
Ancillary studies
Given IV
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- High-risk medulloblastoma defined by any of the following:
- \> 1.5 cm\^2 residual disease for any medulloblastoma histology, or
- Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or
- Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or
- M4 disease
- Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry
- Children less than 8 months of age at the time of definitive surgery with or without measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible for study entry
- Patients with anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
- Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease \< 1.5 cm\^2 are eligible
- Cranial MRI (with and without gadolinium) must be done pre-operatively; post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery; entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (at least 10 days following surgery) prior to study enrollment (with and without gadolinium); patients with MRI evidence of spinal disease are eligible for this study
- Evaluation of lumbar CSF cytology (cytospin preparation for microscopic evaluation) must be performed either pre-operatively or at least 10 days after definitive surgery unless contraindicated
- Patient must have a life expectancy \> 8 weeks
- Patient must have received no prior radiation therapy or chemotherapy other than corticosteroids; corticosteroids are allowable for all patients
- Creatinine clearance or radioisotope glomerular filtration rate \>= 60 mL/min
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (145)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Broward Health Medical Center
Fort Lauderdale, Florida, 33316, United States
Lee Memorial Health System
Fort Myers, Florida, 33901, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Medical Center
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Tulane University School of Medicine
New Orleans, Louisiana, 70112, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
Tufts Children's Hospital
Boston, Massachusetts, 02111, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Michigan State University
East Lansing, Michigan, 48823, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89120, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
Mercy Children's Hospital
Toledo, Ohio, 43608, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Covenant Children's Hospital
Lubbock, Texas, 79410, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, 6008, Australia
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2, Canada
San Jorge Children's Hospital
San Juan, 00912, Puerto Rico
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Claire M Mazewski
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2006
First Posted
June 12, 2006
Study Start
October 22, 2007
Primary Completion
December 31, 2016
Study Completion
September 30, 2025
Last Updated
January 23, 2026
Results First Posted
October 24, 2018
Record last verified: 2026-01