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

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ClinicalTrials.gov Identifier: NCT00020566
Recruitment Status : Unknown
Verified June 2012 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : January 27, 2003
Last Update Posted : June 24, 2014
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Children's Cancer and Leukaemia Group
Societe Francaise Oncologie Pediatrique
European Organisation for Research and Treatment of Cancer - EORTC
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria
Swiss Group for Clinical Cancer Research
EBMT Solid Tumors Working Party
Children's Oncology Group
Information provided by:
National Cancer Institute (NCI)

July 11, 2001
January 27, 2003
June 24, 2014
February 2001
December 2011   (Final data collection date for primary outcome measure)
  • Event-free survival
  • Overall survival
Not Provided
Complete list of historical versions of study NCT00020566 on ClinicalTrials.gov Archive Site
  • Feasibility, toxicity, and response at 1 month following induction therapy
  • Feasibility and toxicity of consolidation regimens at 1 month following consolidation therapy
Not Provided
Not Provided
Not Provided
 
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)

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.

OBJECTIVES:

Primary

  • 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

  • Determine the prognostic significance of EWS-Flil transcript in these patients.
  • 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.
  • Determine the feasibility and toxicity of VIDE induction chemotherapy in these patients.
  • Determine the response of these patients to VIDE induction chemotherapy.
  • Determine the feasibility and toxicity of VAI consolodation chemotherapy in these patients.
  • Determine the feasibility and toxicity of Bu-Mel consolodation chemotherapy in these patients.
  • Determine event-free survival and overall survival of patients treated with these regimens by prognostic group analysis.

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

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

Interventional
Phase 3
Allocation: Randomized
Primary Purpose: Treatment
Sarcoma
  • Biological: dactinomycin
    Given IV
  • Drug: busulfan
    Given orally and IV
  • Drug: doxorubicin hydrochloride
    Given IV
  • Drug: etoposide
    Given IV
  • Drug: ifosfamide
    Given IV
  • Drug: melphalan
    Given orally and IV
  • Drug: vincristine sulfate
    Given IV
  • Procedure: autologous hematopoietic stem cell transplantation
    Given IV
  • Procedure: conventional surgery
    Given to patients deemed to require it
  • Radiation: radiation therapy
    Given to patients deemed to require it
  • Experimental: 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: ifosfamide
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • Experimental: Group 2, arm I
    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.
    Interventions:
    • Biological: dactinomycin
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: ifosfamide
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • Experimental: Group 2, arm II
    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 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: busulfan
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: ifosfamide
    • Drug: melphalan
    • Drug: vincristine sulfate
    • Procedure: autologous hematopoietic stem cell transplantation
    • Procedure: conventional surgery
    • Radiation: radiation therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
1200
Not Provided
Not Provided
December 2011   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 49 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   New Zealand,   Puerto Rico,   United States
Austria,   Belgium,   Denmark,   France,   Germany,   Ireland,   Netherlands,   Portugal,   Switzerland,   United Kingdom
 
NCT00020566
CDR0000068608
EURO-EWING-INTERGROUP-EE99
EBMT-INTERGROUP-EE99
EORTC-62981
GPOH-AUSTRIA-INTERGROUP-EE99
GPOH-GERMANY-INTERGROUP-EE99
SFOP-INTERGROUP-EE99
SWS-SAKK-INTERGROUP-EE99
CCLG-INTERGROUP-EE99
COG-AEWS0331
EU-20213
Not Provided
Not Provided
Not Provided
Not Provided
University of Leicester
  • National Cancer Institute (NCI)
  • Children's Cancer and Leukaemia Group
  • Societe Francaise Oncologie Pediatrique
  • European Organisation for Research and Treatment of Cancer - EORTC
  • Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
  • Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria
  • Swiss Group for Clinical Cancer Research
  • EBMT Solid Tumors Working Party
  • Children's Oncology Group
Study Chair: Alan W. Craft, MD Sir James Spence Institute of Child Health at Royal Victoria Infirmary
Study Chair: Ian J. Lewis, MD Leeds Cancer Centre at St. James's University Hospital
Study Chair: Odile Oberlin, MD Gustave Roussy, Cancer Campus, Grand Paris
Investigator: Ian R. Judson, MA, MD, FRCP Institute of Cancer Research, United Kingdom
Study Chair: Heribert F. Juergens, MD University Hospital Muenster
Study Chair: Helmut Gadner, MD, FRCPG St. Anna Kinderkrebsforschung
Study Chair: G. Ulrich Exner, MD Balgrist Universitaetsklinik
Study Chair: Ruth Ladenstein, MD St. Anna Kinderkrebsforschung
Study Chair: Douglas Hawkins, MD Seattle Children's Hospital
National Cancer Institute (NCI)
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP