Clinical trial · Interventional

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

European Ewing Tumour Working Initiative of National Groups Ewing Tumour Studies 1999 (EURO-E.W.I.N.G.99)

NCT00020566CI-TRIAL-00014906unknownPhase 3ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

RATIONALE: Drugs used in chemotherapy use 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. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without radiation therapy and/or surgery in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work when given with or without peripheral stem cell transplantation, radiation therapy, and/or surgery in treating patients with Ewing's sarcoma.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Sarcoma	Sarcoma	ONTOLOGY_EXACT	0.98

Interventions

Interventions (10)

Intervention	Type	Mapped drug	Match
autologous hematopoietic stem cell transplantation	Procedure	—	UNRESOLVED
busulfan	Drug	Busulfan	ALIAS
conventional surgery	Procedure	—	UNRESOLVED
dactinomycin	Biological	Dactinomycin	ALIAS
doxorubicin hydrochloride	Drug	Doxorubicin	ALIAS
etoposide	Drug	Etoposide	ALIAS
ifosfamide	Drug	Ifosfamide	ALIAS
melphalan	Drug	Melphalan	ALIAS

Design

Arms and outcomes

Arms (3)

type
EXPERIMENTAL
label
Group 1
description
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.
interventionNames
1. Biological: dactinomycin
2. Drug: doxorubicin hydrochloride
3. Drug: etoposide
4. Drug: ifosfamide
5. Drug: vincristine sulfate
6. Procedure: conventional surgery
7. Radiation: radiation therapy
type
EXPERIMENTAL
label
Group 2, arm I
description
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 then 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.

Eligibility

Eligibility (as posted)

Sex: All
Maximum age: 49 Years

Show eligibility criteria text

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

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* See Disease Characteristics

References

Publications (8)

RESULTLadenstein R, Potschger U, Le Deley MC, Whelan J, Paulussen M, Oberlin O, van den Berg H, Dirksen U, Hjorth L, Michon J, Lewis I, Craft A, Jurgens H. Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol. 2010 Jul 10;28(20):3284-91. doi: 10.1200/JCO.2009.22.9864. Epub 2010 Jun 14. PMID 20547982
RESULTLe Deley MC, Delattre O, Schaefer KL, Burchill SA, Koehler G, Hogendoorn PC, Lion T, Poremba C, Marandet J, Ballet S, Pierron G, Brownhill SC, Nesslbock M, Ranft A, Dirksen U, Oberlin O, Lewis IJ, Craft AW, Jurgens H, Kovar H. 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. 2010 Apr 20;28(12):1982-8. doi: 10.1200/JCO.2009.23.3585. Epub 2010 Mar 22. PMID 20308673
RESULTJuergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Juergens H, Craft A. 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. 2006 Jul;47(1):22-9. doi: 10.1002/pbc.20820. PMID 16572419
DERIVEDStork T, Ranft A, Aigner C, Jurgens H, Ladenstein RL, Timmermann B, Van den Berg H, Dirksen U, Collaud S. Primary Mediastinal Ewing's Sarcoma: Post Hoc Analysis from Two International Multicenter Prospective Randomized Trials. Cancers (Basel). 2025 Jan 2;17(1):118. doi: 10.3390/cancers17010118. PMID 39796745
DERIVEDRechl V, Ranft A, Bhadri V, Brichard B, Collaud S, Cyprova S, Eich H, Ek T, Gelderblom H, Hardes J, Haveman LM, Hartmann W, Hauser P, Heesen P, Jurgens H, Kanerva J, Kuhne T, Raciborska A, Rascon J, Streitburger A, Uhlenbruch Y, Timmermann B, Kersting J, Pham MT, Dirksen U. Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum. Sarcoma. 2024 Mar 16;2024:4751914. doi: 10.1155/2024/4751914. eCollection 2024. PMID 38524902

Registry

Dates and enrollment

Start: Feb 1, 2001
Primary completion: Dec 1, 2011
Completion: —
First posted: Jan 27, 2003
Last update posted: Jun 24, 2014
Enrollment: 1,200 (estimated)
Lead sponsor: University of Leicester OTHER
Collaborators: National Cancer Institute (NCI); Children's Cancer and Leukaemia Group; Societe Francaise Oncologie Pediatrique; European Organisation for Research and Treatment of Cancer - EORTC; German Society for Pediatric Oncology and Hematology GPOH gGmbH; Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria; Swiss Cancer Institute; EBMT Solid Tumors Working Party; Children's Oncology Group
Keywords: localized Ewing sarcoma/peripheral primitive neuroectodermal tumor, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Data updated 22 days agoSource updated Jun 24, 2014source: clinicaltrials

Locations

Locations by country (103)

Country	Sites	Recruiting
United States