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NCT00006734 · CITED IN SOURCE DOCUMENTS

Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor

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
COMPLETED
Registry last update
2023-08-03

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.

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 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
healthy Volunteers
false
maximum Age
50 Years
minimum Age
0 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Biological: filgrastim
    2. Drug: cyclophosphamide
    3. Drug: doxorubicin hydrochloride
    4. Drug: etoposide
    5. Drug: ifosfamide
    6. Drug: vincristine sulfate
    7. Procedure: adjuvant therapy
    8. Procedure: conventional surgery
    9. Procedure: neoadjuvant therapy
    10. Radiation: brachytherapy
    11. Radiation: radiation therapy
    label
    Regimen A
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Biological: filgrastim
    2. Drug: cyclophosphamide
    3. Drug: doxorubicin hydrochloride
    4. Drug: etoposide
    5. Drug: ifosfamide
    6. Drug: vincristine sulfate
    7. Procedure: adjuvant therapy
    8. Procedure: conventional surgery
    9. Procedure: neoadjuvant therapy
    10. Radiation: brachytherapy
    11. Radiation: radiation therapy
    label
    Regimen B
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    filgrastim
    other Names
    1. GRANULOCYTE COLONY-STIMULATING FACTOR
    2. r-metHuG-CSF
    3. G-CSF
    4. Neupogen
    5. NSC 614629
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    cyclophosphamide
    other Names
    1. CTX
    2. Cytoxan
    3. NSC #026271
    type
    DRUG
  3. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    doxorubicin hydrochloride
    other Names
    1. Adriamycin
    2. NSC #123127
    3. IND #7038
    type
    DRUG
  4. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    etoposide
    other Names
    1. VP-16
    2. VePesid
    3. Etopophos
    4. NSC #141540
    type
    DRUG
  5. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    ifosfamide
    other Names
    1. Ifex
    2. NSC #109724
    type
    DRUG
  6. arm Group Labels
    1. Regimen A
    2. Regimen B
    description
    Given IV
    name
    vincristine sulfate
    other Names
    1. Oncovin
    2. NSC #067574
    type
    DRUG
  7. arm Group Labels
    1. Regimen A
    2. Regimen B
    name
    adjuvant therapy
    type
    PROCEDURE
  8. arm Group Labels
    1. Regimen A
    2. Regimen B
    name
    conventional surgery
    type
    PROCEDURE
  9. arm Group Labels
    1. Regimen A
    2. Regimen B
    name
    neoadjuvant therapy
    type
    PROCEDURE
  10. arm Group Labels
    1. Regimen A
    2. Regimen B
    name
    brachytherapy
    type
    RADIATION
  11. arm Group Labels
    1. Regimen A
    2. Regimen B
    name
    radiation therapy
    type
    RADIATION
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
587
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Assessed using a two sided log rank test of 0.05.
    measure
    Event-free survival
    time Frame
    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
Full study description
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.
detailed Description
OBJECTIVES: * Compare the effect of interval-compressed vs standard chemotherapy in terms of event-free survival and overall survival in patients with newly diagnosed, localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic). Patients are randomized to 1 of 2 treatment arms for induction and continuation therapy. * Induction therapy (weeks 1-12): * Arm I: Patients receive alternating courses of chemotherapy consisting of vincristine IV on day 1, doxorubicin IV continuously over 48 hours on days 1 and 2, and cyclophosphamide IV over 1 hour on day 1 for courses 1 and 3 and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 for courses 2 and 4. Beginning 24 hours after the last dose of chemotherapy for each course, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Treatment continues every 3 weeks for 4 courses. * Arm II: Patients receive alternating courses of chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide as in arm I for courses 1, 3, and 5 and ifosfamide and etoposide as in arm I for courses 2, 4, and 6. Patients also receive G-CSF as in arm I. Treatment continues every 2 weeks for 6 courses. After completion of induction therapy, patients in both arms receive local control treatment to the primary tumor. Patients receive continuation chemotherapy after surgery or concurrently with radiotherapy. * Continuation therapy: * Arm I (weeks 13-42): Patients receive additional alternating courses of chemotherapy as in arm I of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 7 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 3 weeks for 10 courses. * Arm II (weeks 13-29): Patients receive additional alternating courses of chemotherapy as in arm II of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 9 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 2 weeks for 8 courses. Patients are followed every 3 months for 4 years and then every 6 months for 1 year. PROJECTED ACCRUAL: Approximately 528 patients will be accrued for this study within 4-5 years.
Source references
references
  1. citation
    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.
    pmid
    20308669
    type
    BACKGROUND
  2. citation
    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.
    pmid
    23091096
    type
    RESULT
  3. citation
    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.
    pmid
    21480204
    type
    RESULT
  4. citation
    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.
    type
    RESULT
  5. citation
    Cash T, Krailo MD, Buxton AB, Pawel BR, Healey JH, Binitie O, Marcus KJ, Grier HE, Grohar PJ, Reed DR, Weiss AR, Gorlick R, Janeway KA, DuBois SG, Womer RB. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031. J Clin Oncol. 2023 Oct 20;41(30):4724-4728. doi: 10.1200/JCO.23.00053. Epub 2023 Aug 31.
    pmid
    37651654
    type
    DERIVED
  6. citation
    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.
    pmid
    28787430
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        ="_2522" tabindex="-1">A retrospective analysis examined patients treated on two Children's Oncology Group (COG) studies, INT-0154 and <a href="/clinicaltrials/NCT00006734">AEWS0031 (NCT00006734)</a>. This study compared the clinical characteristics of 213 patients with extraskeletal primary Ewing sarcoma with those of 826 patien
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        l of whom were excluded from the EURO-EWING-INTERGROUP-EE99 study.</li></ul></div></li><li>In a Children's Oncology Group (COG) study (<a href="/clinicaltrials/NCT00006734">COG-AEWS0031 [NCT00006734]</a>), patients presenting without metastases were randomly assigned to receive cycles of VDC alternating with cycles of IE at eith
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        m the EURO-EWING-INTERGROUP-EE99 study.</li></ul></div></li><li>In a Children's Oncology Group (COG) study (<a href="/clinicaltrials/NCT00006734">COG-AEWS0031 [NCT00006734]</a>), patients presenting without metastases were randomly assigned to receive cycles of VDC alternating with cycles of IE at either 2-week or 3-week interva
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        sarcoma.[<a href="#cit/section_5.24">24</a>,<a href="#cit/section_5.74">74</a>] In a review of data from the POG-9354 (INT-0154) and <a href="/clinicaltrials/NCT00006734">EWS0031 (NCT00006734)</a> studies, 213 patients with extraosseous Ewing sarcoma and 826 patients with Ewing sarcoma of bone were identified.[<a href="#cit/sec
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        t/section_5.24">24</a>,<a href="#cit/section_5.74">74</a>] In a review of data from the POG-9354 (INT-0154) and <a href="/clinicaltrials/NCT00006734">EWS0031 (NCT00006734)</a> studies, 213 patients with extraosseous Ewing sarcoma and 826 patients with Ewing sarcoma of bone were identified.[<a href="#cit/section_5.75">75</a>][<a
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        yclophosphamide for the duration of treatment.[<a href="#cit/section_7.13">13</a>]</li><li>In a Children's Oncology Group (COG) trial (<a href="/clinicaltrials/NCT00006734">COG-AEWS0031 [NCT00006734]</a>), 568 patients with newly diagnosed localized extradural Ewing sarcoma were randomly assigned to receive chemotherapy (VDC/IE)
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        ation of treatment.[<a href="#cit/section_7.13">13</a>]</li><li>In a Children's Oncology Group (COG) trial (<a href="/clinicaltrials/NCT00006734">COG-AEWS0031 [NCT00006734]</a>), 568 patients with newly diagnosed localized extradural Ewing sarcoma were randomly assigned to receive chemotherapy (VDC/IE) given either every 2 weeks
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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