Trial record 1 of 1 for:    NCT00336024
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Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00336024
First received: June 8, 2006
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. 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.


Condition Intervention Phase
Untreated Childhood Medulloblastoma
Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
Drug: etoposide
Drug: cyclophosphamide
Drug: cisplatin
Biological: filgrastim
Drug: carboplatin
Drug: thiotepa
Drug: methotrexate
Drug: leucovorin calcium
Drug: vincristine sulfate
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Versus the Same Therapy Without Methotrexate

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Complete response (CR) rate [ Time Frame: From baseline to up to 4 years ] [ Designated as safety issue: No ]
    The analysis of response will be based on a one-sided, two-sample test of proportions, with Type I error of 10%. Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transverse (T), and length (L) measurements.


Secondary Outcome Measures:
  • Time to treatment failure defined as disease progression or recurrence, death from any cause, or occurrence of a second malignant neoplasm [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: No ]

    The analysis of event-free survival (EFS) will be based on a proportional hazards, non-mixture parametric cure model (PCM).

    Partial stratification will be accomplished by separately estimating the scale parameter of the Weibull kernel function within each of the patient arms.


  • Toxicity rates of acute, chronic, and late effects of the two intense regimens [ Time Frame: From the beginning of treatment to end of study, assessed up to 4 years ] [ Designated as safety issue: Yes ]
    Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Patients who have progression or recurrence of disease will be censored in these analyses. Differences in incidence for treatment regimens will be tested with the log-rank test for overall pattern.

  • Rates of gastrointestinal and nutritional toxicities [ Time Frame: In each course or treatment ] [ Designated as safety issue: Yes ]
    Rates of gastrointestinal and nutritional toxicities will be summarized using standard descriptive statistical methods. The two groups will be compared using a Chi-square test to detect a significant difference in complications between the two groups.

  • Quality of life and neuropsychological (NP) scores as assessed by the Children Oncology Group (COG) Standard Neuropsychological and Behavioral Battery [ Time Frame: From baseline to up to 4 years ] [ Designated as safety issue: No ]
    Parent-report questionnaires will be completed to gather information about the patient's function, specifically in terms of attention, memory, executive abilities, and behavioral/social/emotional adaptation. Long-term effects of treatment on neuropsychological and quality of life outcomes will be primarily descriptive. Correlational analyses will be conducted, with Pearson product moment correlations computed for continuous data and chi-square analyses conducted for discrete data.

  • Gene expression profiling by northern blotting or by gel electrophoresis [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    The methods used by Golub and colleagues and Pomeroy and colleagues, as well as standard statistical techniques such as Cox regression analysis will be used in these analyses. Internal cross-validation procedures, such as the leave-one-out method, will be utilized in the training set to provide less-biased estimates of correct classification rates.


Estimated Enrollment: 96
Study Start Date: August 2007
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (induction+consolidation chemotherapy, autologous PBSC))

Patients receive vincristine sulfate IV 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 filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplantation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (induction+consolidation chemotherapy, autologous PBSC)

Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally 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 filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplantation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:

    • High-risk medulloblastoma defined by any of the following:

      • Residual disease > 1.5 cm²
      • Lumbar cerebral spinal fluid cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or ≥ 10 days after definitive surgery unless contraindicated
      • M0 disease in children < 8 months of age at diagnosis
      • M2 or M3 metastatic disease by MRI
      • M4 disease
    • Supratentorial primitive neuroectodermal tumor (PNET)(any M-stage)
    • Anaplastic medulloblastoma regardless of M-stage or residual tumor
    • M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2
  • MRI evidence of spinal disease
  • Tumor must be negative for INI1 gene
  • Has undergone definitive surgery within the past 31 days
  • No atypical teratoid rhabdoid tumors
  • Biological specimens must be available for correlative laboratory studies
  • Life expectancy > 8 weeks
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2 times ULN
  • Shortening fraction ≥ 27% by echocardiogram
  • Ejection fraction ≥ 47% by radionuclide angiogram
  • No evidence of dyspnea at rest
  • Pulse oximetry > 94% on room air
  • Absolute neutrophil count > 1,000/mm³
  • Platelet count > 100,000/mm³ (transfusion independent)
  • Hemoglobin > 8 g/dL (RBC transfusions allowed)
  • Prior corticosteroids allowed
  • No prior radiation therapy or chemotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336024

  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Children's Hospital Central California
Madera, California, United States, 93636-8762
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Sutter General Hospital
Sacramento, California, United States, 95816
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Broward Health Medical Center
Fort Lauderdale, Florida, United States, 33316
Lee Memorial Health System
Fort Myers, Florida, United States, 33901
University of Florida
Gainesville, Florida, United States, 32610
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Miami Children's Hospital
Miami, Florida, United States, 33155
Nemours Childrens Clinic - Orlando
Orlando, Florida, United States, 32806
M D Anderson Cancer Center- Orlando
Orlando, Florida, United States, 32806
Florida Hospital
Orlando, Florida, United States, 32803
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
Saint Mary's Hospital
West Palm Beach, Florida, United States, 33407
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
Memorial Health University Medical Center
Savannah, Georgia, United States, 31403
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Idaho
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States, 83712
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Advocate Hope Children's Hospital
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States, 46260
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maine
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
United States, Massachusetts
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, United States, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, United States, 49008
Michigan State University - Breslin Cancer Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States, 07503
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Winthrop University Hospital
Mineola, New York, United States, 11501
Columbia University Medical Center
New York, New York, United States, 10032
New York University Langone Medical Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
University of Rochester
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Presbyterian Hospital
Charlotte, North Carolina, United States, 28204
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
Mercy Children's Hospital
Toledo, Ohio, United States, 43608
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, United States, 43606
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States, 97227
Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-2001
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
Greenville Cancer Treatment Center
Greenville, South Carolina, United States, 29605
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
United States, South Dakota
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States, 57117-5134
United States, Tennessee
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Tech University Health Science Center-Amarillo
Amarillo, Texas, United States, 79106
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98405
United States, Wisconsin
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Sydney Children's Hospital
Randwick, New South Wales, Australia, 2031
The Children's Hospital at Westmead
Sydney, New South Wales, Australia, 2145
Australia, Victoria
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Chedoke-McMaster Hospitals
Hamilton, Ontario, Canada, L8S 4L8
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada, H3H 1P3
Hospital Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Claire Mazewski, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00336024     History of Changes
Other Study ID Numbers: ACNS0334, NCI-2009-00338, COG-ACNS0334, CDR0000483683, U10CA098543
Study First Received: June 8, 2006
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Glioma
Etoposide phosphate
Cisplatin
Carboplatin
Cyclophosphamide
Thiotepa
Vincristine
Methotrexate
Etoposide
Lenograstim
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 19, 2014