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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00006734




Registration number
NCT00006734
Ethics application status
Date submitted
6/12/2000
Date registered
27/01/2003
Date last updated
3/08/2023

Titles & IDs
Public title
Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor
Scientific title
Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors
Secondary ID [1] 0 0
COG-AEWS0031
Secondary ID [2] 0 0
AEWS0031
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - filgrastim
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - ifosfamide
Treatment: Drugs - vincristine sulfate

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.

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.


Treatment: Other: filgrastim
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: doxorubicin hydrochloride
Given IV

Treatment: Drugs: etoposide
Given IV

Treatment: Drugs: ifosfamide
Given IV

Treatment: Drugs: vincristine sulfate
Given IV
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival
Timepoint [1] 0 0
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

Eligibility
Key inclusion criteria
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
Minimum age
0 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2001
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2023
Sample size
Target
Accrual to date
Final
587
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Louisiana
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Maine
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Massachusetts
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New Jersey
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New Mexico
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New York
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Tennessee
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Utah
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Vermont
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Washington
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West Virginia
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Alberta
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British Columbia
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Manitoba
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Canada
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Canada
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Saskatchewan
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Netherlands
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Groningen
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New Zealand
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Auckland
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Puerto Rico
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San Juan
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Puerto Rico
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Santurce
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Switzerland
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Bern
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Switzerland
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Geneva
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Switzerland
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Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
SWOG Cancer Research Network
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00006734
Trial related presentations / 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. doi: 10.1200/JCO.2015.61.1491. 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.
Public notes

Contacts
Principal investigator
Name 0 0
Richard B. Womer, MD
Address 0 0
Children's Hospital of Philadelphia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00006734