Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor

Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which chemotherapy regimen combined with radiation therapy and/or surgery is more effective in treating Ewing's sarcoma or primitive neuroectodermal tumor.

PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens combined with radiation therapy and/or surgery in treating patients who have Ewing's sarcoma or primitive neuroectodermal tumor.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: cyclophosphamide; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: etoposide; Radiation: brachytherapy; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Biological: filgrastim; Drug: ifosfamide

Detailed Description

OBJECTIVES:

• Compare the effect of interval-compressed vs standard chemotherapy in terms of event-free survival and overall survival in patients with newly diagnosed, localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic). Patients are randomized to 1 of 2 treatment arms for induction and continuation therapy.

• Induction therapy (weeks 1-12):

  • Arm I: Patients receive alternating courses of chemotherapy consisting of vincristine IV on day 1, doxorubicin IV continuously over 48 hours on days 1 and 2, and cyclophosphamide IV over 1 hour on day 1 for courses 1 and 3 and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 for courses 2 and 4. Beginning 24 hours after the last dose of chemotherapy for each course, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Treatment continues every 3 weeks for 4 courses.
  • Arm II: Patients receive alternating courses of chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide as in arm I for courses 1, 3, and 5 and ifosfamide and etoposide as in arm I for courses 2, 4, and 6. Patients also receive G-CSF as in arm I. Treatment continues every 2 weeks for 6 courses.

After completion of induction therapy, patients in both arms receive local control treatment to the primary tumor. Patients receive continuation chemotherapy after surgery or concurrently with radiotherapy.

• Continuation therapy:

  • Arm I (weeks 13-42): Patients receive additional alternating courses of chemotherapy as in arm I of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 7 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 3 weeks for 10 courses.
  • Arm II (weeks 13-29): Patients receive additional alternating courses of chemotherapy as in arm II of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 9 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 2 weeks for 8 courses.

Patients are followed every 3 months for 4 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: Approximately 528 patients will be accrued for this study within 4-5 years.

• Study Type: Interventional
• Enrollment (Actual): 587
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Sydney Children's Hospital
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Children's Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Janeway Children's Health and Rehabilitation Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4J9
      • McMaster Children's Hospital at Hamilton Health Sciences
    • London, Ontario, Canada, N6C 2V5
      • Children's Hospital of Western Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital Of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal Children's Hospital at McGill University Health Center
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Health
• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus
  • Santurce, Puerto Rico, 00912
    • San Jorge Children's Hospital
• Switzerland
  • Bern, Switzerland, CH 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, CH 1211
    • Swiss Pediatric Oncology Group Geneva
  • Lausanne, Switzerland, CH 1011
    • Swiss Pediatric Oncology Group Lausanne
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Comprehensive Cancer Center at University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Cancer Research Institute
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Downey, California, United States, 90242
      • Southern California Permanente Medical Group
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Long Beach, California, United States, 90801-1428
      • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90027-0700
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Oakland, California, United States, 94609-1809
      • Children's Hospital and Research Center at Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford University Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
    • San Diego, California, United States, 92123-4282
      • Children's Hospital and Health Center - San Diego
    • San Francisco, California, United States, 94143
      • UCSF Comprehensive Cancer Center
    • Santa Barbara, California, United States, 93102
      • Santa Barbara Cottage Hospital
    • Santa Clara, California, United States, 95051-5386
      • Kaiser Permanente Medical Center - Santa Clara
    • Travis Air Force Base, California, United States, 94535
      • General Robert Huyser Cancer Center at David Grant Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Presbyterian - St. Luke's Medical Center
    • Denver, Colorado, United States, 80218
      • Children's Hospital Cancer Center
  • Connecticut
    • Farmington, Connecticut, United States, 06360-7106
      • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
    • New Haven, Connecticut, United States, 06520-8064
      • Yale Comprehensive Cancer Center
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Fort Myers, Florida, United States, 33908
      • Children's Hospital of Southwest Florida
    • Gainesville, Florida, United States, 32610-0296
      • University of Florida Shands Cancer Center
    • Hollywood, Florida, United States, 33021
      • Joe DiMaggio Children's Hospital at Memorial
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
    • Miami, Florida, United States, 33176-2197
      • Baptist-South Miami Regional Cancer Program
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic-Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Children's Hospital
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33677-4227
      • St. Joseph's Children's Hospital of Tampa
    • West Palm Beach, Florida, United States, 33407
      • Kaplan Cancer Center at St. Mary's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
    • Augusta, Georgia, United States, 30912-4000
      • MBCCOP-Medical College of Georgia Cancer Center
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
    • Savannah, Georgia, United States, 31405
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Mountain States Tumor Institute - Boise
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
    • Chicago, Illinois, United States, 60601
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Hope Children's Hospital
    • Park Ridge, Illinois, United States, 60068-1174
      • Lutheran General Cancer Care Center
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
    • Springfield, Illinois, United States, 62794-9658
      • Southern Illinois University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5225
      • Riley Children Cancer Center at Riley Hospital for Children
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Hospitals and Health Care Centers
  • Iowa
    • Des Moines, Iowa, United States, 50308
      • Blank Children's Hospital
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Louisville, Kentucky, United States, 40202-3830
      • Kosair Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital of New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Cancer Institute at Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
  • Maine
    • Bangor, Maine, United States, 04401
      • Pediatric Specialty Clinic at Eastern Maine Medical Center
    • Scarborough, Maine, United States, 04074-9308
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
    • Baltimore, Maryland, United States, 21201-1595
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21231-7223
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children
    • Springfield, Massachusetts, United States, 01107
      • Baystate Regional Cancer Program at D'Amour Center for Cancer Care
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0914
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • Detroit, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • DeVos Children's Hospital
    • Kalamazoo, Michigan, United States, 49007-5364
      • Bronson Methodist Hospital
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
    • Royal Oak, Michigan, United States, 48073-6769
      • William Beaumont Hospital - Royal Oak Campus
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's - Duluth Clinic Cancer Center
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics - Minneapolis/St. Paul
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital of Omaha
    • Omaha, Nebraska, United States, 68198-2168
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Cancer Center at Hackensack University Medical Center
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • Newark, New Jersey, United States, 07112-2094
      • Newark Beth Israel Medical Center
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
    • Summit, New Jersey, United States, 07901
      • Valerie Fund Children's Center at Atlantic Health
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Research and Treatment Center
  • New York
    • Albany, New York, United States, 12208
      • Children's Hospital at Albany Medical Center
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11212
      • Brookdale University Hospital and Medical Center
    • Brooklyn, New York, United States, 11201-5493
      • Brooklyn Hospital Center
    • Brooklyn, New York, United States, 11219
      • Comprehensive Cancer Center at Maimonides Medical Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794-8174
      • Long Island Cancer Center at Stony Brook University Hospital
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27858-4354
      • Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital
  • North Dakota
    • Fargo, North Dakota, United States, 58103-4940
      • Dakota Cancer Institute at Innovis Health - Dakota Clinic
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43205-2696
      • Columbus Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Children's Medical Center - Dayton
    • Toledo, Ohio, United States, 43601
      • Toledo Children's Hospital
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital - Forum Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Children's Hospital at Oklahoma University Medical Center
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center & Children's Hospital
    • Portland, Oregon, United States, 97239-3098
      • Doernbecher Children's Hospital at Oregon Health & Science University
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-1320
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Children's Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Hollings Cancer Center at Medical University of South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health South Carolina Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Children's Hospital of Greenville Hospital System
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105-1080
      • Avera Cancer Institute
  • Tennessee
    • Johnson City, Tennessee, United States, 37614-0622
      • East Tennessee State University Cancer Center at Johnson City Medical Center
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232-6310
      • Vanderbilt Children's Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75390-9063
      • Simmons Cancer Center at University of Texas Southwestern Medical Center at Dallas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Galveston, Texas, United States, 77555-0209
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
    • Lackland Air Force Base, Texas, United States, 78236
      • Wilford Hall Medical Center
    • Lackland Air Force Base, Texas, United States, 78236
      • San Antonio Military Pediatric Cancer and Blood Disorders Center
    • Lubbock, Texas, United States, 79410
      • Covenant Children's Hospital
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229-3900
      • MBCCOP - South Texas Pediatrics
    • San Antonio, Texas, United States, 78229-3902
      • Methodist Cancer Center at Methodist Specialty and Transplant Hospital
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
    • Temple, Texas, United States, 76508
      • Center for Cancer Prevention and Care at Scott and White Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center at University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Falls Church, Virginia, United States, 22042-3300
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Portsmouth, Virginia, United States, 23708-5100
      • Naval Medical Center - Portsmouth
    • Richmond, Virginia, United States, 23298-0212
      • Massey Cancer Center at Virginia Commonwealth University
    • Roanoke, Virginia, United States, 24029
      • Carilion Medical Center for Children at Roanoke Community Hospital
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Hospital Community Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98273
      • Cancer Care Center at Skagit Valley Hospital
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Seattle, Washington, United States, 98114
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99210-0248
      • Deaconess Medical Center
    • Tacoma, Washington, United States, 98431-0001
      • Madigan Army Medical Center
    • Wenatchee, Washington, United States, 98801
      • Central Washington Hospital
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Clinic
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
    • Huntington, West Virginia, United States, 25701
      • Cabell Huntington Hospital
    • Morgantown, West Virginia, United States, 26506-9300
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • CCOP - St. Vincent Hospital Cancer Center, Green Bay
    • Green Bay, Wisconsin, United States, 54301
      • Bellin Memorial Hospital
    • Green Bay, Wisconsin, United States, 54307-9070
      • St. Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Comprehensive Cancer Center
    • Madison, Wisconsin, United States, 53792-6164
      • Medical College of Ohio Cancer Institute
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Clinic Research Foundation
    • Marshfield, Wisconsin, United States, 54449-5772
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor (PNET) of the bone or soft tissues

  • Diagnostic biopsy of primary tumor within 30 days of study

• Paraspinal or bony skull tumors of extradural origin allowed

  • No intradural soft tissue tumors

• Askin's tumor of the chest wall allowed

  • Chest wall tumors with ipsilateral pleural effusions or ipsilateral pleural-based secondary tumor nodules allowed
  • No contralateral pleural effusions

• No metastatic disease or distant node involvement

  • One pulmonary or pleural nodule greater than 1 cm in diameter OR more than 1 nodule greater than 0.5 cm in diameter are considered pulmonary metastasis
  • Solitary lung nodules of 0.5-1 cm OR multiple nodules of 0.3-0.5 cm allowed unless biopsy positive for tumor
• Light microscopic appearance (hematoxylin and eosin stained) consistent with Ewing's sarcoma or peripheral PNET
• No immunohistochemical or ultrastructural evidence of rhabdomyosarcoma
• No esthesioneuroblastoma
• Clinically or pathologically involved regional lymph nodes allowed
• No CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 50 and under at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine normal for age
• Creatinine clearance or isotope glomerular filtration rate at least 75 mL/min

Cardiovascular:

• Shortening fraction at least 28% by echocardiography OR
• Ejection fraction at least 55% by radionuclide angiogram

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior malignancy except skin cancer diagnosed at least 5 years ago and currently in remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for skin cancer
• No concurrent sargramostim (GM-CSF)
• No concurrent pegfilgrastim

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Prior complete or partial excision of primary tumor allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regimen A; Test the hypothesis that chemotherapy given every two weeks (Regimen B) will produce higher event-free survival. Treatment will occur in two phases: Induction and Continuation, with 14 cycles of chemotherapy in all. Induction consists of the first twelve weeks (four cycles on Regimen A. The cycles alternate between vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, MESNA and ifosfamide, etoposide, MESNA. G-CSF (Filgrastim) is given between chemotherapy doses. Local control (Surgery, Radiation Therapy, or a combination) will begin on Week 13 which will be after four cycles of chemotherapy.	Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; NSC #026271; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: etoposide; Given IV; Other Names: VP-16; Etopophos; VePesid; NSC #141540; Radiation: brachytherapy; Drug: doxorubicin hydrochloride; Given IV; Other Names: Adriamycin; NSC #123127; IND #7038; Drug: vincristine sulfate; Given IV; Other Names: Oncovin; NSC #067574; Biological: filgrastim; Given IV; Other Names: G-CSF; r-metHuG-CSF; Neupogen; GRANULOCYTE COLONY-STIMULATING FACTOR; NSC 614629; Drug: ifosfamide; Given IV; Other Names: Ifex; NSC #109724
Experimental: Regimen B; Conventional every-three-week chemotherapy for patients with Ewing sarcoma and related tumors. Treatment will occur in two phases: Induction and Continuation, with 14 cycles of chemotherapy in all. Induction consists of the first twelve weeks six cycles on Regimen B). The cycles alternate between vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, MESNA and ifosfamide etoposide MESNA. G-CSF (Filgrastim) is given between chemotherapy doses. Local control (surgery, Radiation Therapy, or a combination) will begin on Week 13, which will be after six cycles of chemotherapy.	Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; NSC #026271; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: etoposide; Given IV; Other Names: VP-16; Etopophos; VePesid; NSC #141540; Radiation: brachytherapy; Drug: doxorubicin hydrochloride; Given IV; Other Names: Adriamycin; NSC #123127; IND #7038; Drug: vincristine sulfate; Given IV; Other Names: Oncovin; NSC #067574; Biological: filgrastim; Given IV; Other Names: G-CSF; r-metHuG-CSF; Neupogen; GRANULOCYTE COLONY-STIMULATING FACTOR; NSC 614629; Drug: ifosfamide; Given IV; Other Names: Ifex; NSC #109724

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	Assessed using a two sided log rank test of 0.05.	Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI); SWOG Cancer Research Network
• Investigators: Study Chair: Richard B. Womer, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• van Doorninck JA, Ji L, Schaub B, Shimada H, Wing MR, Krailo MD, Lessnick SL, Marina N, Triche TJ, Sposto R, Womer RB, Lawlor ER. Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2010 Apr 20;28(12):1989-94. doi: 10.1200/JCO.2009.24.5845. Epub 2010 Mar 22.
• Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, Weiss AR. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-54. doi: 10.1200/JCO.2011.41.5703. Epub 2012 Oct 22. Erratum In: J Clin Oncol. 2015 Mar 1;33(7):814. Dosage error in article text.
• Borinstein SC, Barkauskas DA, Krailo M, Scher D, Scher L, Schlottmann S, Kallakury B, Dickman PS, Pawel BR, West DC, Womer RB, Toretsky JA. Investigation of the insulin-like growth factor-1 signaling pathway in localized Ewing sarcoma: a report from the Children's Oncology Group. Cancer. 2011 Nov 1;117(21):4966-76. doi: 10.1002/cncr.26112. Epub 2011 Apr 8.
• Womer RB, West DC, Krailo MD, et al.: Randomized comparison of every-two-week v. every-three-week chemotherapy in Ewing sarcoma family tumors (ESFT). [Abstract] J Clin Oncol 26 (Suppl 15): A-10504, 2008.
• Mora J, Castaneda A, Perez-Jaume S, Lopez-Pousa A, Maradiegue E, Valverde C, Martin-Broto J, Garcia Del Muro X, Cruz O, Cruz J, Martinez-Trufero J, Maurel J, Vaz MA, de Alava E, de Torres C. GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS). Br J Cancer. 2017 Sep 5;117(6):767-774. doi: 10.1038/bjc.2017.252. Epub 2017 Aug 8.

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: December 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Ifosfamide; Lenograstim; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: AEWS0031; COG-AEWS0031 (Other Identifier: Children's Oncology Group); CDR0000068323 (Other Identifier: Clinical Trials.gov); A7983 (Other Identifier: Children's Cancer Group)