Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation, Radiation Therapy, and/or Surgery in Treating Patients With Ewing's Sarcoma

Basic Trial Information

Objectives

Primary

1. Compare the event-free and overall survival of patients with tumor of the Ewing's family treated with standard induction chemotherapy comprising vincristine, dactinomycin, ifosfamide and etoposide (VIDE) followed by consolidation chemotherapy comprising vincristine, dactinomycin, and ifosfamide versus high-dose busulfan and melphalan (Bu-Mel) followed by autologous peripheral blood stem cell (PBSC) transplantation with or without radiotherapy and/or surgery.

Secondary

1. Determine the prognostic significance of EWS-Flil transcript in these patients.
2. Determine the frequency and prognostic value of minimal disease in bone marrow and PBSC, as determined by the presence or absence of EWS-Flil transcript, in these patients.
3. Determine the feasibility and toxicity of VIDE induction chemotherapy in these patients.
4. Determine the response of these patients to VIDE induction chemotherapy.
5. Determine the feasibility and toxicity of VAI consolodation chemotherapy in these patients.
6. Determine the feasibility and toxicity of Bu-Mel consolodation chemotherapy in these patients.
7. Determine event-free survival and overall survival of patients treated with these regimens by prognostic group analysis.

Entry Criteria

Disease Characteristics:

• Histologically confirmed tumor of the Ewing's family of bone or soft tissue
  • Ewing's sarcoma
  • Peripheral primitive neuroectodermal tumor

• Disease meeting one of the following criteria:
  • Resectable localized disease (tumor volume less than 200 mL)
  • Localized disease previously resected at diagnosis
  • Unresectable disease (at least 200 mL tumor volume) but radiotherapy as local control can be delayed
  • Localized disease with early radiotherapy required
  • Pulmonary and/or pleural metastases only
  • Extrapulmonary/pleural metastases (skeleton, bone marrow, lymph nodes)

• No more than 45 days since definitive biopsy

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• Under 50

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Renal function normal
• Glomerular filtration rate at least 60 mL/min

Cardiovascular:

• Normal cardiac function
• Fractional shortening at least 29%
• Ejection fraction at least 40%

Other:

• No medical, psychiatric, or social condition that would preclude study participation

Expected Enrollment

Approximately 1,200 patients will be accrued for this study within approximately 7 years.

Outcomes

Event-free survival
Overall survival

Feasibility, toxicity, and response at 1 month following induction therapy
Feasibility and toxicity of consolidation regimens at 1 month following consolidation therapy

Outline

This is a randomized, multicenter study. Patients are stratified according to age and local treatment of the primary tumor (yes vs no).

Patients receive induction chemotherapy comprising vincristine IV on day 1 and ifosfamide IV over 3 hours, doxorubicin IV over 4 hours, and etoposide IV over 1 hour on days 1-3 (VIDE). Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity. Peripheral blood stem cells (PBSC) are collected after course 3 and/or 4. Patients are evaluated after course 4. Patients in need of early radiotherapy due to an axial tumor or patients who require radiotherapy to the brain and/or spinal cord (at any time during study) are assigned to group 1. Patients not needing early radiotherapy are assigned to group 2.

• Group 1: Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy.

• Group 2: Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients are randomized to 1 of 2 consolidation therapy arms.
  • Arm I: Patients receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days.

  • Arm II: Patients receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Ladenstein R, Pötschger U, Le Deley MC, et al.: Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol 28 (20): 3284-91, 2010.[PUBMED Abstract]

Le Deley MC, Delattre O, Schaefer KL, et al.: Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol 28 (12): 1982-8, 2010.[PUBMED Abstract]

Juergens C, Weston C, Lewis I, et al.: Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer 47 (1): 22-9, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

University Hospitals of Leicester NHS Trust

Alan Craft, MD, Protocol chair		Ph: 44-191-202-3033

Children's Cancer and Leukaemia Group

Ian Lewis, MD, Protocol chair		Ph: 44-113-206-4985 Email: ian.lewis@leedsth.nhs.uk

Societe Francaise Oncologie Pediatrique

Odile Oberlin, MD, Protocol chair		Ph: 33-1-42-114-180 Email: oberlin@igr.fr

European Organization for Research and Treatment of Cancer

Ian Judson, MA, MD, FRCP, Study coordinator		Ph: 44-20-8722-4303

Gesellschaft fuer Paediatrische Onkologie und Haematologie - Germany

Heribert Juergens, MD, Protocol chair		Ph: 49-251-834-7742 Email: jurgh@uni-muenster.de

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria

Helmut Gadner, MD, FRCPG, Protocol chair		Ph: 43-1-401-70-1250

Swiss Group for Clinical Cancer Research

G. Ulrich Exner, MD, Protocol chair		Ph: 41-1-386-3090 Email: guexner@wiss.balgrist.ch

EBMT Solid Tumors Working Party

Ruth Ladenstein, MD, Protocol chair		Ph: 43-1-404-700

Children's Oncology Group

Douglas Hawkins, MD, Protocol chair		Ph: 206-987-3096

U.S.A.
Alabama
	Birmingham
	UAB Comprehensive Cancer Center
		Clinical Trials Office - UAB Comprehensive Cancer Center	Ph:  205-934-0309
Arizona
	Phoenix
	Phoenix Children's Hospital
		Jessica Boklan	Ph:  602-546-0920
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph:  323-361-2529
	Southern California Permanente Medical Group
		Robert Cooper	Ph:  323-783-5307
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Neyssa Marina	Ph:  650-723-5535
	Sacramento
	Kaiser Permanente Medical Center - Oakland
		Vincent Kiley	Ph:  916-474-2326
	San Diego
	Rady Children's Hospital - San Diego
		Clinical Trials Office - Rady Children's Hospital - San Diego	Ph:  858-966-5934
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Colorado
	Aurora
	Children's Hospital Colorado Center for Cancer and Blood Disorders
		Kelly Maloney	Ph:  720-777-6673
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Clinical Trials Office - Alfred I. duPont Hospital for Children	Ph:  302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Clinical Trials Office - Children's National Medical Center	Ph:  202-884-2549
Florida
	Jacksonville
	Nemours Children's Clinic
		Eric Sandler	Ph:  904-697-3793
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		University of Miami Sylvester Comprehensive Cancer Center Clinical Trial Matching Service	Ph:  866-574-5124
			Email: Sylvester@emergingmed.com
	Orlando
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph:  407-650-7230
	Pensacola
	Nemours Children's Clinic - Pensacola
		Jeffrey Schwartz	Ph:  850-505-4790
	Saint Petersburg
	All Children's Hospital
		Gregory Hale	Ph:  727-767-4176
	Tampa
	St. Joseph's Cancer Institute at St. Joseph's Hospital
		Clinical Trials Office - St. Joseph's Cancer Institute	Ph:  800-882-4123
	West Palm Beach
	Kaplan Cancer Center at St. Mary's Medical Center
		Narayana Gowda	Ph:  561-844-6363
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Todd Cooper	Ph:  404-785-1838
Hawaii
	Honolulu
	Cancer Research Center of Hawaii
		Clinical Trials Office - Cancer Research Center of Hawaii	Ph:  808-586-2979
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		Eugenia Chang	Ph:  208-381-2731
Illinois
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Peoria
	Saint Jude Midwest Affiliate
		Pedro De Alarcon	Ph:  309-655-4242
	Springfield
	Simmons Cooper Cancer Institute
		Clinical Trials Office - Simmons Cooper Cancer Institute	Ph:  217-545-7929
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Cancer Information Service	Ph:  800-237-1225
Kentucky
	Louisville
	Kosair Children's Hospital
		Clinical Trials Office - Kosair Children's Hospital	Ph:  502-629-5500
			Email: CancerResource@nortonhealthcare.org
Louisiana
	New Orleans
	Children's Hospital of New Orleans
		Clinical Trials Office - Children's Hospital of New Orleans	Ph:  504-894-5377
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Joseph Wiley	Ph:  410-601-6266
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Carlos Rodriguez-Galindo	Ph:  617-632-4580
Michigan
	Flint
	Hurley Medical Center
		Clinical Trials Office - Hurley Medical Center	Ph:  810-762-8057
	Grand Rapids
	Helen DeVos Children's Hospital at Spectrum Health
		Clinical Trials Office - Helen DeVos Children's Hospital	Ph:  616-391-3050
	Grosse Pointe Woods
	Van Elslander Cancer Center at St. John Hospital and Medical Center
		Clincial Trials Office - Van Elslander Cancer Center at St. John Hospital and Medical Center	Ph:  313-343-3166
	Kalamazoo
	Bronson Methodist Hospital
		Jeffrey Lobel	Ph:  269-341-6350
	Lansing
	Breslin Cancer Center at Ingham Regional Medical Center
		Clinical Trials Office - Breslin Cancer Center at Ingham Regional Medical Center	Ph:  517-334-2765
Minnesota
	Duluth
	CCOP - Duluth
		Contact Person	Ph:  218-786-8364
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Clinical Trials Office - Children's Hospitals and Clinics of Minnesota	Ph:  612-813-5193
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	St. Paul
	Children's Hospitals and Clinics of Minnesota - St. Paul
		Contact Person	Ph:  612-220-6000
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail Megason	Ph:  601-984-5220
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine Hetherington	Ph:  816-234-3265
	St. Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Robert Hayashi	Ph:  314-454-2041
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		Jonathan Bernstein	Ph:  702-732-1493
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Clinical Trials Office - Hackensack University Medical Center Cancer Center	Ph:  201-996-2879
New York
	Bronx
	Albert Einstein Cancer Center at Albert Einstein College of Medicine
		Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine	Ph:  718-904-2730
			Email: aecc@aecom.yu.edu
	Buffalo
	Roswell Park Cancer Institute
		Clinical Trials Office - Roswell Park Cancer Institute	Ph:  877-275-7724
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Clinical Trials Office - Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Ph:  212-305-8615
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Lisa Hackney	Ph:  585-275-2981
	Syracuse
	SUNY Upstate Medical University Hospital
		Clinical Trials Office - SUNY Upstate Medical University Hospital	Ph:  315-464-5476
North Carolina
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Clinical Trials Office - Blumenthal Cancer Center at Carolinas Medical Center	Ph:  704-355-2884
	Presbyterian Cancer Center at Presbyterian Hospital
		Clinical Trials Office - Presbyterian Cancer Center at Presbyterian Hospital	Ph:  704-384-5369
	Durham
	Duke Cancer Institute
		Clinical Trials Office - Duke Cancer Institute	Ph:  888-275-3853
	Greenville
	Leo W. Jenkins Cancer Center at ECU Medical School
		Clinical Trials Office - Leo W. Jenkins Cancer Center at ECU Medical School	Ph:  252-744-2391
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-2799
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100
	Rainbow Babies and Children's Hospital
		Yousif (Joe) Matloub	Ph:  216-844-3345
	Columbus
	Nationwide Children's Hospital
		Laura Martin	Ph:  614-722-3582
	Dayton
	Dayton Children's - Dayton
		Emmett Broxson	Ph:  937-641-3111
	Toledo
	Toledo Hospital
		Clinical Trials Office - Toledo Hospital	Ph:  419-824-1842
	Youngstown
	Tod Children's Hospital
		Clinical Trials Office - Tod Children's Hospital	Ph:  330-884-3955
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene McNall-Knapp	Ph:  405-271-5311
Oregon
	Portland
	Legacy Emanuel Children's Hospital
		Clinical Trials Office - Legacy Emanuel Children's Hospital	Ph:  503-413-2560
Pennsylvania
	Bethlehem
	Lehigh Valley Hospital - Muhlenberg
		Philip Monteleone	Ph:  484-884-3333
	Hershey
	Penn State Children's Hospital
		John Kuttesch	Ph:  717-531-6012
	Philadelphia
	Children's Hospital of Philadelphia
		Elizabeth Fox	Ph:  267-425-3010
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Clinical Trials Office - Children's Hospital of Pittsburgh	Ph:  412-692-7056
South Carolina
	Greenville
	Greenville Hospital Cancer Center
		Clinical Trials Office - Greenville Hospital Cancer Center	Ph:  864-241-6251
South Dakota
	Sioux Falls
	Avera Cancer Institute
		Contact Person	Ph:  605-322-3000
Tennessee
	Knoxville
	East Tennessee Children's Hospital
		Ray Pais	Ph:  865-541-8266
Texas
	Amarillo
	Texas Tech University Health Sciences Center School of Medicine - Amarillo
		Osvaldo Regueira	Ph:  806-354-5434x282
	Corpus Christi
	Driscoll Children's Hospital
		Clinical Trials Office - Driscoll Children's Hospital	Ph:  361-694-5311
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Clinical Trials Office - Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Ph:  866-460-4673; 214-648-7097
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Clinical Trials Office - Cook's Children's Medical Center	Ph:  682-885-2103
	San Antonio
	Methodist Children's Hospital of South Texas
		Jaime Estrada	Ph:  210-575-7268
	University of Texas Health Science Center at San Antonio
		Anne-Marie Langevin	Ph:  210-567-7477
Utah
	Salt Lake City
	Primary Children's Medical Center
		Phillip Barnette	Ph:  801-662-4700
Virginia
	Charlottesville
	University of Virginia Cancer Center
		Kimberly Dunsmore	Ph:  434-924-5105
	Falls Church
	Inova Fairfax Hospital
		Clinical Trials Office - Inova Fairfax Hospital	Ph:  703-208-6650
	Norfolk
	Children's Hospital of The King's Daughters
		Eric Lowe	Ph:  757-668-7243
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie Park	Ph:  206-987-2106
	Spokane
	Providence Cancer Center at Sacred Heart Medical Center
		Judy Felgenhauer	Ph:  509-474-2777
	Tacoma
	Mary Bridge Children's Hospital and Health Center - Tacoma
		Robert Irwin	Ph:  253-403-3481
West Virginia
	Charleston
	West Virginia University Health Sciences Center - Charleston
		Allen Chauvenet	Ph:  304-388-1552
Wisconsin
	Green Bay
	St. Vincent Hospital Regional Cancer Center
		Clinical Trials Office - St. Vincent Hospital Regional Cancer Center	Ph:  920-433-8889
	Marshfield
	Marshfield Clinic - Marshfield Center
		Clinical Trials Office - Marshfield Clinic - Marshfield Center	Ph:  800-782-1581 ext. 94457
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael Kelly	Ph:  414-456-4170
Australia
New South Wales
	Westmead
	Children's Hospital at Westmead
		Geoffrey McCowage	Ph:  61298452122
Queensland
	Brisbane
	Royal Children's Hospital
		Helen Irving	Ph:  617-3636-8671
South Australia
	North Adelaide
	Women's and Children's Hospital
		Maria Kirby	Ph:  61881617411
Western Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine Cole	Ph:  011-6189340-8238
Canada
Alberta
	Edmonton
	University of Alberta Hospital
		Sunil Jayantilal` Desai	Ph:  780-407-8829
British Columbia
	Vancouver
	Children's and Women's Hospital of British Columbia
		Caron Strahlendorf	Ph:  604-875-3576
Manitoba
	Winnipeg
	CancerCare Manitoba
		Rochelle Yanofsky	Ph:  204-787-4163
Newfoundland and Labrador
	St. John's
	Janeway Children's Health and Rehabilitation Centre
		Lisa Anne Goodyear	Ph:  709-777-4303
Nova Scotia
	Halifax
	IWK Health Centre
		Margaret Yhap	Ph:  902-470-8778
Ontario
	Toronto
	Hospital for Sick Children
		Sylvain Baruchel	Ph:  416-813-7795
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph:  514-345-4969
	Quebec
	Centre Hospitalier Universitaire de Quebec
		Bruno Michon	Ph:  418-656-4141X47191
Saskatchewan
	Saskatoon
	Saskatoon Cancer Centre at the University of Saskatchewan
		Christopher Mpofu	Ph:  306-655-2744
New Zealand
	Auckland
	Starship Children's Health
		Lochie Teague	Ph:  649-307-4949x22423
Puerto Rico
	Santurce
	San Jorge Children's Hospital
		Luis Clavell	Ph:  787-728-1575

Registry Information
Official Title		European Ewing Tumour Working Initiative of National Groups Ewing Tumour Studies 1999 (EURO-E.W.I.N.G.99)
Trial Start Date		2001-02-09
Trial Completion Date		2011-12-30 (estimated)
Registered in ClinicalTrials.gov		NCT00020566
Date Submitted to PDQ		2001-03-05
Information Last Verified		2012-05-26
NCI Grant/Contract Number		CA98543

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