Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
NCT ID: NCT00336024
Last Updated: 2026-01-23
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
91 participants
INTERVENTIONAL
2007-10-22
2025-09-30
Brief Summary
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Detailed Description
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I. To determine if treatment of infants with high risk primitive neuroectodermal tumors (PNET) central nervous system (CNS) tumors with intensive chemotherapy plus high-dose methotrexate and peripheral blood stem cell rescue results in a higher complete response rate then the same regimen without methotrexate.
SECONDARY OBJECTIVES:
I. To determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors (AT/RT) from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs.
II. To determine if event free survival (EFS) and patterns of failure differ between the methotrexate arm versus the arm without methotrexate.
III. To compare the acute, chronic and late effects of these two very intensive regimens, especially as to the tolerance of the same consolidation regimen following the differing induction regimens.
IV. To compare the gastrointestinal and nutritional toxicities of these intense regimens.
V. To describe and compare the quality of life outcomes and neuropsychological effects of these intense systemic therapies.
OUTLINE: Patients are randomized to 1 of 2 treatment arms
INDUCTION THERAPY:
ARM I: Patients 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; and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients 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 orally (PO) every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Once 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. Patients also receive G-CSF IV or SC beginning 24 hours after the completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
In both arms, patients with stable disease or partial response after induction therapy proceed to second-look surgery followed by consolidation therapy. Patients with a complete response after induction therapy proceed directly to consolidation therapy.
CONSOLIDATION THERAPY: Beginning no more than 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 peripheral blood stem cells (PBSC) IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically for 4 years and then annually thereafter.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (induction+consolidation chemotherapy, autologous PBSC)
Patients 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.
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC resuce
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Thiotepa
Given IV
Vincristine Sulfate
Given IV
Arm II (induction+consolidation chemotherapy, autologous PBSC)
Patients 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.
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC resuce
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Leucovorin Calcium
Given IV or orally
Methotrexate
Given IV
Quality-of-Life Assessment
Ancillary studies
Thiotepa
Given IV
Vincristine Sulfate
Given IV
Interventions
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Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC resuce
Carboplatin
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Etoposide
Given IV
Filgrastim
Given IV or SC
Laboratory Biomarker Analysis
Correlative studies
Leucovorin Calcium
Given IV or orally
Methotrexate
Given IV
Quality-of-Life Assessment
Ancillary studies
Thiotepa
Given IV
Vincristine Sulfate
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* \> 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
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamic pyruvic transaminase (SGPT) (alanine transaminase \[ALT\]) \< 2 x ULN for age
* Shortening fraction \>= 27% by echocardiogram, or
* Ejection fraction \>= 47% by radionuclide angiogram
* No evidence of dyspnea at rest
* Pulse oximetry \> 94% on room air
* Peripheral absolute neutrophil count (ANC) \> 1,000/uL
* Platelet count \> 100,000/uL (transfusion independent)
* Hemoglobin greater than 8 g/dL (may have received red blood cell \[RBC\] transfusions allowed)
* Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
* Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal excretion of methotrexate is inhibited by these agents
* Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
* Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine) should be avoided
* Clinically significant drug interactions have been reported when using vincristine with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors and inducers; selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine
* 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
2 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Claire M Mazewski
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
Children's Hospital of Orange County
Orange, California, United States
Sutter Medical Center Sacramento
Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Broward Health Medical Center
Fort Lauderdale, Florida, United States
Lee Memorial Health System
Fort Myers, Florida, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Saint Mary's Medical Center
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
Eastern Maine Medical Center
Bangor, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Tufts Children's Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Michigan State University
East Lansing, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States
Overlook Hospital
Summit, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
NYU Langone Hospital - Long Island
Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
New York Medical College
Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
Sanford Broadway Medical Center
Fargo, North Dakota, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, United States
Mercy Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Covenant Children's Hospital
Lubbock, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
University of Vermont and State Agricultural College
Burlington, Vermont, United States
Inova Fairfax Hospital
Falls Church, Virginia, United States
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Children's Hospital
Parkville, Victoria, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Alberta Children's Hospital
Calgary, Alberta, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
IWK Health Centre
Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
Kingston, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, , Canada
San Jorge Children's Hospital
San Juan, , Puerto Rico
Countries
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Other Identifiers
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NCI-2009-00338
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000483683
Identifier Type: -
Identifier Source: secondary_id
07-654
Identifier Type: -
Identifier Source: secondary_id
ACNS0334
Identifier Type: -
Identifier Source: secondary_id
COG-ACNS0334
Identifier Type: -
Identifier Source: secondary_id
ACNS0334
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS0334
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS0334
Identifier Type: -
Identifier Source: org_study_id
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