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NCT00020566 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
UNKNOWN
Registry last update
2014-06-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility 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 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
healthy Volunteers
false
maximum Age
49 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  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.
    intervention Names
    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
    label
    Group 1
    type
    EXPERIMENTAL
  2. 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.
    intervention Names
    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
    label
    Group 2, arm I
    type
    EXPERIMENTAL
  3. 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 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.
    intervention Names
    1. Biological: dactinomycin
    2. Drug: busulfan
    3. Drug: doxorubicin hydrochloride
    4. Drug: etoposide
    5. Drug: ifosfamide
    6. Drug: melphalan
    7. Drug: vincristine sulfate
    8. Procedure: autologous hematopoietic stem cell transplantation
    9. Procedure: conventional surgery
    10. Radiation: radiation therapy
    label
    Group 2, arm II
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given IV
    name
    dactinomycin
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Group 2, arm II
    description
    Given orally and IV
    name
    busulfan
    type
    DRUG
  3. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given IV
    name
    doxorubicin hydrochloride
    type
    DRUG
  4. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given IV
    name
    etoposide
    type
    DRUG
  5. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given IV
    name
    ifosfamide
    type
    DRUG
  6. arm Group Labels
    1. Group 2, arm II
    description
    Given orally and IV
    name
    melphalan
    type
    DRUG
  7. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given IV
    name
    vincristine sulfate
    type
    DRUG
  8. arm Group Labels
    1. Group 2, arm II
    description
    Given IV
    name
    autologous hematopoietic stem cell transplantation
    type
    PROCEDURE
  9. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given to patients deemed to require it
    name
    conventional surgery
    type
    PROCEDURE
  10. arm Group Labels
    1. Group 1
    2. Group 2, arm I
    3. Group 2, arm II
    description
    Given to patients deemed to require it
    name
    radiation therapy
    type
    RADIATION
Study design
allocation
RANDOMIZED
primary Purpose
TREATMENT
Enrollment
count
1200
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Event-free survival
  2. measure
    Overall survival
secondary Outcomes
  1. measure
    Feasibility, toxicity, and response at 1 month following induction therapy
  2. measure
    Feasibility and toxicity of consolidation regimens at 1 month following consolidation therapy
Full study description
brief Summary
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.
detailed Description
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.
Source references
references
  1. citation
    Ladenstein 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
    type
    RESULT
  2. citation
    Le 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
    type
    RESULT
  3. citation
    Juergens 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
    type
    RESULT
  4. citation
    Stork 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
    type
    DERIVED
  5. citation
    Rechl 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
    type
    DERIVED
  6. citation
    Corvest V, Marec-Berard P, Lervat C, Pacquement H, Toulmonde M, Gentet JC, Laurence V, Cleirec M, Mansuy L, Bompas E, Castex MP, Taque S, Filhon B, Tabone MD, Verite C, Entz-Werle N, Saumet L, Guimard G, Pondrom M, Chevreau C, Flandrin J, Duranteau L, Rousset-Jablonski C, Brugieres L, Jimenez M, Le Deley MC, Gaspar N, Fresneau B. Late toxicity comparison of alkylating-based maintenance regimen with cyclophosphamide (VAC) vs ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro-EWING99-R1 in France. Int J Cancer. 2023 Apr 15;152(8):1659-1667. doi: 10.1002/ijc.34326. Epub 2022 Oct 31.
    pmid
    36250317
    type
    DERIVED
  7. citation
    Dirksen U, Brennan B, Le Deley MC, Cozic N, van den Berg H, Bhadri V, Brichard B, Claude L, Craft A, Amler S, Gaspar N, Gelderblom H, Goldsby R, Gorlick R, Grier HE, Guinbretiere JM, Hauser P, Hjorth L, Janeway K, Juergens H, Judson I, Krailo M, Kruseova J, Kuehne T, Ladenstein R, Lervat C, Lessnick SL, Lewis I, Linassier C, Marec-Berard P, Marina N, Morland B, Pacquement H, Paulussen M, Randall RL, Ranft A, Le Teuff G, Wheatley K, Whelan J, Womer R, Oberlin O, Hawkins DS; Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. J Clin Oncol. 2019 Dec 1;37(34):3192-3202. doi: 10.1200/JCO.19.00915. Epub 2019 Sep 25.
    pmid
    31553693
    type
    DERIVED
  8. citation
    Le Deley MC, Paulussen M, Lewis I, Brennan B, Ranft A, Whelan J, Le Teuff G, Michon J, Ladenstein R, Marec-Berard P, van den Berg H, Hjorth L, Wheatley K, Judson I, Juergens H, Craft A, Oberlin O, Dirksen U. Cyclophosphamide compared with ifosfamide in consolidation treatment of standard-risk Ewing sarcoma: results of the randomized noninferiority Euro-EWING99-R1 trial. J Clin Oncol. 2014 Aug 10;32(23):2440-8. doi: 10.1200/JCO.2013.54.4833. Epub 2014 Jun 30.
    pmid
    24982464
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        emotherapy):</p> <div class="pdq-content-list"><ol id="_396"><li>An international consortium of European countries conducted the <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial from 2000 to 2010.[<a href="#cit/section_5.28">28</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017
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        ntent-list"><ol id="_396"><li>An international consortium of European countries conducted the <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial from 2000 to 2010.[<a href="#cit/section_5.28">28</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017&amp;version=HealthProfessional&amp;langu
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      3. context exact
        iation therapy alone, or surgery plus radiation therapy.[<a href="#cit/section_5.32">32</a>]</p> <p id="_1953" tabindex="-1">The <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial prospectively treated 180 patients with pelvic primary tumors without clinically detectable metastatic dise
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      4. context exact
        iation therapy.[<a href="#cit/section_5.32">32</a>]</p> <p id="_1953" tabindex="-1">The <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial prospectively treated 180 patients with pelvic primary tumors without clinically detectable metastatic disease.[<a href="#cit/section_5.33">33</a>][
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      5. context exact
        ents who are anticipated to have suboptimal surgery should be considered for definitive radiation therapy.</li></ul></div></li><li>The <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> study reported the outcomes of 599 patients who presented with localized disease and had surgical resection after
        end
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      6. context exact
        al surgery should be considered for definitive radiation therapy.</li></ul></div></li><li>The <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> study reported the outcomes of 599 patients who presented with localized disease and had surgical resection after initial chemotherapy with at least 90% n
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        role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial for two distinct groups:[<a href="#cit/section_5.69">69</a>]<div class="pdq-content-list"><ol id="_1876" cl
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      8. context exact
        melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial for two distinct groups:[<a href="#cit/section_5.69">69</a>]<div class="pdq-content-list"><ol id="_1876" class="lower-alpha"><li>Patients who presen
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        role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial for two distinct groups:[<a href="#cit/section_7.33">33</a>]<div class="pdq-content-list"><ol id="_1890" cl
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        melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial for two distinct groups:[<a href="#cit/section_7.33">33</a>]<div class="pdq-content-list"><ol id="_1890" class="lower-alpha"><li>Patients who presen
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      11. context exact
        TreoMel-HDT and patients in the control arm (20.9% vs. 19.2%; median follow-up, 3.3 years).</li><li>One of the largest studies was the <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99</a> R3 trial that enrolled 281 patients with primary disseminated metastatic Ewing sarcoma. Patients were treated with six cycles
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        role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized <a href="/clinicaltrials/NCT00020566">EURO-EWING-INTERGROUP-EE99 (NCT00020566)</a> trial. Among patients with isolated pulmonary metastases, there was no difference in 3-year EFS rates (55.7% with
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      Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: November 27, 2024
        datetime
        2024-11-27T12:00:00Z
        display
        November 27, 2024

    Preserved source evidence · Not medical advice