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Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma

Primary Purpose

Sarcoma

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
cyclophosphamide
dexrazoxane hydrochloride
doxorubicin hydrochloride
etoposide
ifosfamide
topotecan hydrochloride
vincristine sulfate
conventional surgery
radiation therapy
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring localized Ewing sarcoma/peripheral primitive neuroectodermal tumor

Eligibility Criteria

undefined - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules allowed Contralateral pleural effusions or pleural nodules are not eligible Tumor arising in the bony skull (extradural) are eligible Tumors arising in the intradural soft tissue are not eligible Newly diagnosed disease Only have had a biopsy of the primary tumor without an attempt at complete or partial resection Prior attempted or accomplished unplanned excision allowed provided adequate imaging was obtained prior to surgery AND resection considered incomplete and further local control required No evidence of metastatic disease, defined as lesions discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor No evidence of metastatic lung disease by CT scan One pulmonary nodule > 1 cm in diameter OR > 1 nodule > 0.5 cm in diameter are considered evidence of pulmonary metastasis Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed negative by biopsy Solitary nodules < 0.5 cm or multiple nodules < 0.3 cm not considered clear evidence of lung disease No distant nodule disease No esthesioneuroblastoma PATIENT CHARACTERISTICS: Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients ≥ 16 years of age or Lansky PS 50-100% for patients < 16 years of age) Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT < 2.5 times ULN Shortening fraction ≥ 27% by EKG Ejection fraction ≥ 50% by radionuclide angiogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiotherapy No prior chemotherapy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Arm I

    Arm II

    Arm Description

    Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19.

    Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients also undergo local therapy comprising of conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Patients then proceed to combination chemotherapy.

    Outcomes

    Primary Outcome Measures

    Event-free survival

    Secondary Outcome Measures

    Survival form study enrollment

    Full Information

    First Posted
    June 7, 2006
    Last Updated
    June 27, 2013
    Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00334867
    Brief Title
    Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma
    Official Title
    A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2013
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    withdrawn
    Study Start Date
    December 2005 (undefined)
    Primary Completion Date
    January 2006 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    5. Study Description

    Brief Summary
    RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying combination chemotherapy and topotecan to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed localized Ewing's sarcoma.
    Detailed Description
    OBJECTIVES: Primary Compare the event-free and overall survival of patients with newly diagnosed localized Ewing's sarcoma treated with doxorubicin hydrochloride, cyclophosphamide, vincristine, etoposide, and ifosfamide with vs without topotecan hydrochloride. Compare the side effects of these regimens in these patients. Secondary Evaluate initial tumor size as a prognostic factor for event-free survival of these patients. Evaluate histological response as a prognostic factor for event-free survival of these patients. Continue evaluation of biologic markers both as related to prognosis and as eventual therapeutic targets via encouraging concurrent enrollment on COG-AEWS02B1. Evaluate radiologic response by positron emission tomography as a prognostic factor for event-free survival. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (≤ 17 vs ≥ 18 years of age) and primary tumor site (pelvic vs nonpelvic [including extra-osseous Ewing's sarcoma]). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-30, 34-36, 40-42, and 46-51; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 and doxorubicin hydrochloride as above in weeks 19 and 28; cyclophosphamide as above in weeks 19, 28, 34, 40, 46, and 49; and ifosfamide and etoposide as above in weeks 22, 25, 31, 37, and 43. Arm II: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-33, 37-42, and 46-48; topotecan hydrochloride as above in weeks 19, 31, and 40; cyclophosphamide IV over 30 minutes in weeks 19, 31, and 40 and IV over 1 hour in weeks 28, 37, and 46; ifosfamide and etoposide as above in weeks 22, 25, 34, 43, and 49; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 in weeks 37 and 46; and doxorubicin hydrochloride as above in weeks 28, 37, and 46. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 528 patients will be accrued for this study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sarcoma
    Keywords
    localized Ewing sarcoma/peripheral primitive neuroectodermal tumor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm I
    Arm Type
    Active Comparator
    Arm Description
    Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19.
    Arm Title
    Arm II
    Arm Type
    Experimental
    Arm Description
    Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients also undergo local therapy comprising of conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Patients then proceed to combination chemotherapy.
    Intervention Type
    Drug
    Intervention Name(s)
    cyclophosphamide
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    dexrazoxane hydrochloride
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    doxorubicin hydrochloride
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    etoposide
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    ifosfamide
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    topotecan hydrochloride
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    vincristine sulfate
    Intervention Description
    Given IV
    Intervention Type
    Procedure
    Intervention Name(s)
    conventional surgery
    Intervention Description
    Patients undergo surgery in week 18
    Intervention Type
    Procedure
    Intervention Name(s)
    radiation therapy
    Intervention Description
    Patients undergo radiation therapy in week 19
    Primary Outcome Measure Information:
    Title
    Event-free survival
    Secondary Outcome Measure Information:
    Title
    Survival form study enrollment

    10. Eligibility

    Sex
    All
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules allowed Contralateral pleural effusions or pleural nodules are not eligible Tumor arising in the bony skull (extradural) are eligible Tumors arising in the intradural soft tissue are not eligible Newly diagnosed disease Only have had a biopsy of the primary tumor without an attempt at complete or partial resection Prior attempted or accomplished unplanned excision allowed provided adequate imaging was obtained prior to surgery AND resection considered incomplete and further local control required No evidence of metastatic disease, defined as lesions discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor No evidence of metastatic lung disease by CT scan One pulmonary nodule > 1 cm in diameter OR > 1 nodule > 0.5 cm in diameter are considered evidence of pulmonary metastasis Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed negative by biopsy Solitary nodules < 0.5 cm or multiple nodules < 0.3 cm not considered clear evidence of lung disease No distant nodule disease No esthesioneuroblastoma PATIENT CHARACTERISTICS: Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients ≥ 16 years of age or Lansky PS 50-100% for patients < 16 years of age) Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT < 2.5 times ULN Shortening fraction ≥ 27% by EKG Ejection fraction ≥ 50% by radionuclide angiogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiotherapy No prior chemotherapy
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mason Bond, MD
    Organizational Affiliation
    Children's & Women's Hospital of British Columbia
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Leo Mascarenhas, MD
    Organizational Affiliation
    Children's Hospital Los Angeles
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma

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