- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00047320
Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors
A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells.
PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.
Studieoversigt
Status
Detaljeret beskrivelse
OBJECTIVES:
- Determine the response rate of patients with non-germinomatous germ cell tumors treated with neoadjuvant chemotherapy.
- Determine the progression-free survival and overall survival of patients treated with neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy with or without autologous peripheral blood stem cell transplantation (PBSCT).
- Determine whether additional complete responses can be achieved after high-dose thiotepa and etoposide with PBSCT in patients with persistently positive markers, histological evidence of residual malignant elements, or unresectable residual tumors after initial neoadjuvant chemotherapy.
- Determine patterns of recurrence in patients treated with this regimen.
- Correlate tumor marker response with radiographic and clinical measures of response, as well as findings at second-look surgery in patients with radiological evidence of residual disease.
OUTLINE:
Induction chemotherapy:
- Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts recover. Courses are 3 weeks in duration.
- Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in duration.
Patients undergo re-evaluation. Patients with a complete response (CR) go directly to radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients with less than a CR are encouraged to undergo second-look surgery.
After second-look surgery, patients with a CR or a partial response (PR) go directly to radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral blood stem cell rescue (PBSC) followed by radiotherapy.
- Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0. Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC daily.
- Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks beginning after recovery from induction chemotherapy or second-look surgery or within 9 weeks after PBSC reinfusion.
Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42 months.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Queensland
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Brisbane, Queensland, Australien, 4029
- Royal Children's Hospital
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Victoria
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Parkville, Victoria, Australien, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, Australien, 6001
- Princess Margaret Hospital for Children
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Quebec, Canada, G1V 4G2
- Centre Hospitalier Universitaire de Quebec
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- Children's & Women's Hospital of British Columbia
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1B 3V6
- Janeway Children's Health and Rehabilitation Centre
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3K 6R8
- IWK Health Centre
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Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3H 1P3
- Montreal Children's Hospital at McGill University Health Center
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Montreal, Quebec, Canada, H3T 1C5
- Hopital Sainte Justine
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7N 4H4
- Saskatoon Cancer Centre at the University of Saskatchewan
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-
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Alabama
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Birmingham, Alabama, Forenede Stater, 35294
- Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
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Arizona
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Phoenix, Arizona, Forenede Stater, 85016-7710
- Phoenix Children's Hospital
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Arkansas
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Little Rock, Arkansas, Forenede Stater, 72205
- Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
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California
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Downey, California, Forenede Stater, 90242-2814
- Southern California Permanente Medical Group
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Loma Linda, California, Forenede Stater, 92354
- Loma Linda University Cancer Institute at Loma Linda University Medical Center
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Long Beach, California, Forenede Stater, 90801
- Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
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Los Angeles, California, Forenede Stater, 90027
- Childrens Hospital Los Angeles
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Madera, California, Forenede Stater, 93638-8762
- Children's Hospital Central California
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Oakland, California, Forenede Stater, 94609
- Children's Hospital and Research Center Oakland
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Orange, California, Forenede Stater, 92868
- Children's Hospital of Orange County
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Sacramento, California, Forenede Stater, 95816
- Sutter Cancer center
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San Diego, California, Forenede Stater, 92123-4282
- Rady Children's Hospital - San Diego
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San Francisco, California, Forenede Stater, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Stanford, California, Forenede Stater, 94305-5824
- Stanford Cancer Center
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Connecticut
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Farmington, Connecticut, Forenede Stater, 06360-2875
- Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
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Delaware
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Wilmington, Delaware, Forenede Stater, 19803
- Alfred I. DuPont Hospital for Children
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District of Columbia
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Washington, District of Columbia, Forenede Stater, 20010-2970
- Children's National Medical Center
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Florida
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Fort Myers, Florida, Forenede Stater, 33901
- Lee Cancer Care of Lee Memorial Health System
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Gainesville, Florida, Forenede Stater, 32610-0232
- University of Florida Shands Cancer Center
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Jacksonville, Florida, Forenede Stater, 32207
- Nemours Children's Clinic
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Miami, Florida, Forenede Stater, 33136
- University of Miami Sylvester Comprehensive Cancer Center - Miami
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Miami, Florida, Forenede Stater, 33155
- Miami Children's Hospital
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Orlando, Florida, Forenede Stater, 32803-1273
- Florida Hospital Cancer Institute at Florida Hospital Orlando
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Pensacola, Florida, Forenede Stater, 32504
- Sacred Heart Cancer Center at Sacred Heart Hospital
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Saint Petersburg, Florida, Forenede Stater, 33701
- All Children's Hospital
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Tampa, Florida, Forenede Stater, 33607
- St. Joseph's Cancer Institute at St. Joseph's Hospital
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West Palm Beach, Florida, Forenede Stater, 33407
- Kaplan Cancer Center at St. Mary's Medical Center
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Winship Cancer Institute of Emory University
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Augusta, Georgia, Forenede Stater, 30912-3730
- MBCCOP - Medical College of Georgia Cancer Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Chicago, Illinois, Forenede Stater, 60637-1470
- University of Chicago Cancer Research Center
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Park Ridge, Illinois, Forenede Stater, 60068-1174
- Advocate Lutheran General Cancer Care Center
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Springfield, Illinois, Forenede Stater, 62794-9677
- Simmons Cooper Cancer Institute
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202-5289
- Indiana University Melvin and Bren Simon Cancer Center
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Indianapolis, Indiana, Forenede Stater, 46260
- St. Vincent Indianapolis Hospital
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Kansas
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Kansas City, Kansas, Forenede Stater, 66160-7357
- Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Forenede Stater, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Boston, Massachusetts, Forenede Stater, 02111
- Floating Hospital for Children at Tufts - New England Medical Center
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Michigan
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Detroit, Michigan, Forenede Stater, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Grand Rapids, Michigan, Forenede Stater, 49503-2560
- Butterworth Hospital at Spectrum Health
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Grosse Pointe Woods, Michigan, Forenede Stater, 48236
- Van Elslander Cancer Center at St. John Hospital and Medical Center
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Lansing, Michigan, Forenede Stater, 48910
- Breslin Cancer Center at Ingham Regional Medical Center
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
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Minneapolis, Minnesota, Forenede Stater, 55455
- Masonic Cancer Center at University of Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic Cancer Center
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Mississippi
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Jackson, Mississippi, Forenede Stater, 39216-4505
- University of Mississippi Cancer Clinic
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Missouri
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Kansas City, Missouri, Forenede Stater, 64108
- Children's Mercy Hospital
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Saint Louis, Missouri, Forenede Stater, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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New Jersey
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Hackensack, New Jersey, Forenede Stater, 07601
- Hackensack University Medical Center Cancer Center
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New Brunswick, New Jersey, Forenede Stater, 08903
- Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
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Newark, New Jersey, Forenede Stater, 07112
- Newark Beth Israel Medical Center
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Paterson, New Jersey, Forenede Stater, 07503
- St. Joseph's Hospital and Medical Center
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New Mexico
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Albuquerque, New Mexico, Forenede Stater, 87131-5636
- University of New Mexico Cancer Center
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New York
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Bronx, New York, Forenede Stater, 10461
- Albert Einstein Cancer Center at Albert Einstein College of Medicine
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New York, New York, Forenede Stater, 10016
- NYU Cancer Institute at New York University Medical Center
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New York, New York, Forenede Stater, 10032
- Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
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Syracuse, New York, Forenede Stater, 13210
- SUNY Upstate Medical University Hospital
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Valhalla, New York, Forenede Stater, 10595
- New York Medical College
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North Carolina
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Charlotte, North Carolina, Forenede Stater, 28232-2861
- Blumenthal Cancer Center at Carolinas Medical Center
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Durham, North Carolina, Forenede Stater, 27710
- Duke Comprehensive Cancer Center
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Ohio
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Akron, Ohio, Forenede Stater, 44308-1062
- Akron Children's Hospital
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Cincinnati, Ohio, Forenede Stater, 45229-3039
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Forenede Stater, 44195
- Cleveland Clinic Taussig Cancer Center
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Columbus, Ohio, Forenede Stater, 43205-2696
- Nationwide Children's Hospital
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Dayton, Ohio, Forenede Stater, 45404-1815
- Children's Medical Center - Dayton
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- Oklahoma University Cancer Institute
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Oregon
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Portland, Oregon, Forenede Stater, 97239-3098
- Oregon Health and Science University Cancer Institute
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Pennsylvania
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Hershey, Pennsylvania, Forenede Stater, 17033-0850
- Penn State Cancer Institute at Milton S. Hershey Medical Center
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Philadelphia, Pennsylvania, Forenede Stater, 19134-1095
- St. Christopher's Hospital for Children
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Philadelphia, Pennsylvania, Forenede Stater, 19104-9786
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forenede Stater, 15213
- Children's Hospital of Pittsburgh
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Rhode Island
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Providence, Rhode Island, Forenede Stater, 02903
- Rhode Island Hospital Comprehensive Cancer Center
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South Carolina
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Charleston, South Carolina, Forenede Stater, 29425
- Hollings Cancer Center at Medical University of South Carolina
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South Dakota
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Sioux Falls, South Dakota, Forenede Stater, 57117-5039
- Sanford Cancer Center at Sanford USD Medical Center
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Tennessee
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Memphis, Tennessee, Forenede Stater, 38105
- St. Jude Children's Research Hospital
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Nashville, Tennessee, Forenede Stater, 37232-6838
- Vanderbilt-Ingram Cancer Center
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Texas
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Austin, Texas, Forenede Stater, 78723
- Dell Children's Medical Center of Central Texas
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Corpus Christi, Texas, Forenede Stater, 78411
- Driscoll Children's Hospital
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Dallas, Texas, Forenede Stater, 75390
- Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
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Fort Worth, Texas, Forenede Stater, 76104
- Cook Children's Medical Center - Fort Worth
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Lubbock, Texas, Forenede Stater, 79410
- Covenant Children's Hospital
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San Antonio, Texas, Forenede Stater, 78229-3993
- Methodist Children's Hospital of South Texas
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San Antonio, Texas, Forenede Stater, 78207
- University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City, Utah, Forenede Stater, 84113-1100
- Primary Children's Medical Center
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Virginia
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Norfolk, Virginia, Forenede Stater, 23507-1971
- Children's Hospital of The King's Daughters
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West Virginia
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Charleston, West Virginia, Forenede Stater, 25302
- West Virginia University Health Sciences Center - Charleston
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Wisconsin
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Green Bay, Wisconsin, Forenede Stater, 54307-3508
- St. Vincent Hospital Regional Cancer Center
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Marshfield, Wisconsin, Forenede Stater, 54449
- Marshfield Clinic - Marshfield Center
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Milwaukee, Wisconsin, Forenede Stater, 53226
- Midwest Children's Cancer Center
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Auckland, New Zealand, 1
- Starship Children's Health
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Christchurch, New Zealand
- Christchurch Hospital
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Bern, Schweiz, 3010
- Swiss Pediatric Oncology Group Bern
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Geneva, Schweiz, 1205
- Swiss Pediatric Oncology Group Geneva
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
DISEASE CHARACTERISTICS:
One of the following diagnoses:
Histologically confirmed intracranial non-germinomatous germ cell tumor (NGGCT) of 1 of the following types:
- Endodermal sinus tumor (yolk sac tumor)
- Embryonal carcinoma
- Choriocarcinoma
- Immature teratoma and teratoma with malignant transformation
- Mixed germ cell tumor
- Histologically confirmed germinoma with elevation of serum/CSF beta human chorionic gonadotropin (HCG) levels greater than 50 mIU/mL or any serum/CSF alpha-fetoprotein (AFP) levels greater than 10 ng/ml or above institutional norm
- Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta HCG levels greater than 50 mIU/mL or AFP levels greater than 10 ng/ml or above institutional norm
- Patients with normal AFP and beta HCG < 50 mIU/mL without histologic diagnosis of a NGGCT or patients with pure germinoma without elevation of tumor marker are ineligible
- Initial diagnosis within the past 31 days
PATIENT CHARACTERISTICS:
Age
- 3 to 24 at diagnosis
Performance status
- No minimum performance level
Life expectancy
- At least 8 weeks
Hematopoietic
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3 (transfusion independent)
- Hemoglobin at least 10.0 g/dL (transfusion allowed)
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- ALT no greater than 2.5 times ULN
Renal
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Pulmonary
- No assisted ventilation
Other
- Seizure disorders allowed
- No patients in status or coma
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Prior corticosteroids allowed
- Concurrent corticosteroids allowed
- Concurrent endocrine replacement therapy allowed (e.g., L-thyroxine, testosterone, estrogen, desmopressin acetate)
- No concurrent growth hormone therapy
Radiotherapy
- Not specified
Surgery
- More than 1 prior surgery allowed
Other
- No other prior therapy for malignancy
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Radiation Therapy (CR from Induction)
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6).
The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity.
Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours.
Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
|
Givet IV
Andre navne:
Givet IV
Andre navne:
Givet IV
Andre navne:
Givet IV
Andre navne:
craniospinal irradiation
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Response to Induction Chemotherapy
Tidsramme: 18 weeks
|
A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
|
18 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
The Probability of Event-free Survival (EFS)
Tidsramme: At 3 years from study entry
|
Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm.
Event-free survival was estimated by KM estimate.
|
At 3 years from study entry
|
|
Progression-free Survival (PFS)
Tidsramme: At 3 years from study entry
|
Progression-free Survival was defined as time from study entry to disease progression or recurrence.
Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis.
Progression -free survival was estimated by KM estimate.
|
At 3 years from study entry
|
|
Overall Survival (OS)
Tidsramme: At 3 years from study entry
|
Overall Survival was defined as time from study entry to death from any cause.
Overall survival was estimated by KM estimate.
|
At 3 years from study entry
|
|
Number of Patients Experiencing Toxic Death
Tidsramme: During chemotherapy (up to 18 weeks)
|
Toxic death, defined as death predominantly attributable to treatment-related causes.
|
During chemotherapy (up to 18 weeks)
|
|
Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
Tidsramme: During chemotherapy(up to 18 weeks)
|
The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.
|
During chemotherapy(up to 18 weeks)
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Stewart Goldman, MD, Ann & Robert H Lurie Children's Hospital of Chicago
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- barndommens kimcelletumor i centralnervesystemet
- barndoms teratom
- tilbagevendende barndoms maligne kimcelletumor
- barndoms choriocarcinom i centralnervesystemet
- embryonal tumor i centralnervesystemet i barndommen
- barndoms germinom i centralnervesystemet
- barndoms centralnervesystem blandet kimcelletumor
- barndoms teratom i centralnervesystemet
- barndoms centralnervesystem blommesæk tumor
- tilbagevendende embryonal tumor i centralnervesystemet i barndommen
Yderligere relevante MeSH-vilkår
- Sygdomme i nervesystemet
- Neoplasmer efter histologisk type
- Neoplasmer efter sted
- Neoplasmer
- Neoplasmer, kimceller og embryonale
- Neoplasmer i nervesystemet
- Neoplasmer i centralnervesystemet
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Antineoplastiske midler, fytogene
- Topoisomerase II-hæmmere
- Topoisomerasehæmmere
- Carboplatin
- Etoposid
- Ifosfamid
- Isophosphamid sennep
- Thiotepa
Andre undersøgelses-id-numre
- ACNS0122
- CDR0000257664 (Anden identifikator: Clinical Trials.gov)
- COG-ACNS0122 (Anden identifikator: Children's Oncology Group)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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