AzTrials
AzTrials

Anaplastic MedulloblastomaPhase 3NCT00336024

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 3 study testing Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin in people with Anaplastic Medulloblastoma and Medulloblastoma, run by Children's Oncology Group at 145 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages Up to 2 years
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
145 sitesin 4 countries
Study dates
22 Oct 2007to 30 Sep 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Up to 2 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 30Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

145 sites in 4 countries.

145 sites in 4 countries

United States129 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Texas Tech University Health Sciences Center-Amarillo

    Amarillo, Texas, 79106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Tufts Children's Hospital

    Boston, Massachusetts, 02111

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Michigan State University

    East Lansing, Michigan, 48823

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Kalamazoo Center for Medical Studies

    Kalamazoo, Michigan, 49008

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Nevada Cancer Research Foundation NCORP

    Las Vegas, Nevada, 89120

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Valley Children's Hospital

    Madera, California, 93636

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois, 60453

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Legacy Emanuel Hospital and Health Center

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708-2197

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada11 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia4 sites

  • Royal Children's Hospital

    Parkville, Victoria, 3052

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

Puerto Rico1 site

  • San Jorge Children's Hospital

    San Juan, 00912

Other trials in Puerto Rico

About this study

Official title: A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children &lt; 36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue vs. the Same Therapy Without Methotrexate

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Carboplatin, Cisplatin, Cyclophosphamide, Etoposide
Medical subject headings
Medulloblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant

    Undergo autologous PBSC resuce

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    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 IV or SC

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV or orally

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • ThiotepaDrug

    Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT00336024
Study groupRoleWhat they receive
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.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carboplatin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Thiotepa; Drug: Vincristine Sulfate
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.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carboplatin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Methotrexate; Other: Quality-of-Life Assessment; Drug: Thiotepa; Drug: Vincristine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At the end of consolidation treatment

Secondary outcomes (14)

  1. Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort

    The number of patients will be reported for this analysis by Molecular Sub-types of MB, CNS-PNETs/EBTs

    Measured: At baseline

  2. Percentage of Participants With Event Free Survival (EFS)

    EFS was defined as time from enrollment to the occurrence of first event (disease progression/relapse, secondary malignancy, death from any cause) or date of last contact for patients who are event-free. The percentage of participants with EFS and 80% confidence interval were provided. The difference in incidence for the two treatment regimens were compared using a one-sided log-rank test with a significance level of 0.1.

    Measured: Baseline to up to 5 years

  3. Patterns of Failure

    The patterns of failure for relapse/disease progression will be provided for patients treated with/without methotrexate drug in three categories, namely local, distant, and both local and distant. The number of patients with each type of failure will be listed per arm. The two groups will be compared to determine if the pattern of failure distribution is different between the two arms using Fisher exact test.

    Measured: Baseline to up to 5 years

  4. Percentage of Participants With Any Acute Adverse Events

    Event is defined as the first occurrence of any acute toxicity. Estimates will be obtained using life-table methods. Patients who have progression or recurrence of disease will be censored in this analysis. Difference in incidence for the two treatment regimens will be compared using log-rank test.

    Measured: Beginning of treatment to the end of consolidation

  5. Number of Participants With Acute Hearing Loss and No Acute Hearing Loss

    Per protocol, hearing was assessed pretreatment and at regular specified intervals during treatment and off therapy, using DPOAE, audiogram or Brainstem Evoked Auditory. Per CTCAE V4.0 grade 3 Hearing impaired is defined as follows; Pediatric (on a 1,2,3,4, 6 and 8 kHz audiogram): hearing loss sufficient to indicate therapeutic intervention, including hearing aids, threshold shift >20 dB at 3 kHz and above in at least one ear, additional speech-language related services as indicated. Per CTCAE V4.0 grade 4 Hearing impaired is defined as follows; Pediatric Audiologic indication for cochlear implant and additional speech-language related services as indicated.

    Measured: Beginning of treatment to the end of consolidation

  6. Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism

    Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. "Normal" and "Abnormal" are defined at each institution by the laboratory standards where the blood tests are run. Primary Hypothyroidism/Subclinical Compensatory Hypothyroidism is defined as patients with Free T4 level less than "Institutional" Normal or equal to "Institutional" Normal with TSH level greater than "Institutional" Normal.

    Measured: Off-treatment up to 9 years

  7. Number of Participants With Chronic Central Hypothyroidism

    Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. "Normal" and "Abnormal" are defined at each institution by the laboratory standards where the blood tests are run. Central Hypothyroidism is defined as Free T4 level less than "Institutional" Normal with TSH less than or equal to "Institutional" Normal.

    Measured: Off-treatment up to 9 years

  8. Number of Participants With Chronic Low Somatomedin C

    Low Somatomedin C is defined as patients with somatomedin C value less than institutional normal. As numbers are too small, descriptive statistics such as number will be reported for this analysis. Growth hormone function was assessed as per ACNS0334 Endocrine Guidelines. Low Somatomedin C levels are defined at each institution by the laboratory standards where the blood tests are run.

    Measured: Off-treatment up to 9 years

  9. Number of Participants With Chronic Diabetes Insipidus

    The number of patients who had "Diabetes Insipidus" and on DDAVP will be reported for this analysis due to small numbers..

    Measured: Beginning of off-treatment to up to 9 years

  10. Number of Participants With Secondary Malignancies

    The number of patients who had secondary malignancy will be reported for this analysis due to small numbers.

    Measured: Off-treatment up to 9 years

  11. Number of Participants With Chronic/Late Hearing Loss and No Chronic/Late Hearing Loss

    The number of patients who are reported to have abnormal hearing, graded according to CTCAE 4.0 or not, with onset while on therapy or when off therapy which persisted after off therapy will be reported and will be compared using Fisher exact test.

    Measured: Off-treatment up to 9 years

  12. Rates of Gastrointestinal Toxicities

    Rates of gastrointestinal toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with gastrointestinal toxicities between the two treatment regimens will be compared using a Chi-square test.

    Measured: Beginning of treatment to the end of consolidation

  13. Rates of Nutritional Toxicities

    Rates of nutritional toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with nutritional toxicities between the two treatment regimens will be compared using a Chi-square test.

    Measured: Beginning of treatment to the end of consolidation

  14. Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI).

    Three tools are used to assess intelligence (IQ) depending on age. The range of IQ scores is 40-160 (mean=100, SD=15); range for the Processing Speed Index (PSI)=45-155. Higher scores represent better functioning. (1) Wechsler Preschool and Primary Scale of Intelligence-4th Edition (WPPSI-IV) is used for ages 2.5 to 6 years. Bug Search and Cancellation subtests are summed to calculate PSI. (2) Wechsler Intelligence Scales for Children-5th Edition (WISC-V) is used for ages 6 - 16 years. Symbol Search and Coding subtests are summed to calculate PSI. (3) Wechsler Adult Intelligence Scales-4th Edition (WAIS-IV) is used for ages 16 and older. Symbol Search and Coding subtests are summed to calculate PSI.

    The Pediatric Quality of Life Inventory Version 4 (PedsQL) measures health-related quality of life (QOL). Parents complete the measure for children ages 2-17, and patients > 18 complete a self-report version. Total scores range from 0-100, with higher scores representing better QOL.

    Measured: 60 months (+/- 3 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2006 (estimated)
  2. Study start22 Oct 2007
  3. Primary completion31 Dec 2016
  4. Study completion30 Sep 2025

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00336024
Sponsor's protocol ID
ACNS0334
Other IDs
NCI-2009-00338, CDR0000483683, 07-654, ACNS0334, COG-ACNS0334, ACNS0334, ACNS0334, U10CA098543
Status last verified
Jan 2026
First submitted
8 Jun 2006
Last updated
23 Jan 2026
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin in people with Anaplastic Medulloblastoma and Medulloblastoma, run by Children's Oncology Group at 145 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 30 inclusion and 0 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: finished, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 145 sites in United States, Canada, Australia, Puerto Rico. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate (time frame: At the end of consolidation treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00336024.

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 Jan 2026.

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