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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00334867
First received: June 7, 2006
Last updated: January 2, 2009
Last verified: October 2008
History of Changes
  Purpose

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.


Condition Intervention Phase
Sarcoma
 Drug: cyclophosphamide
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Procedure: conventional surgery
Procedure: radiation therapy
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival form study enrollment [ Designated as safety issue: No ]

Estimated Enrollment: 528
Study Start Date: December 2005
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
 Drug: cyclophosphamide
Given IV
Drug: dexrazoxane hydrochloride
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV
Drug: vincristine sulfate
Given IV
Procedure: conventional surgery
Patients undergo surgery in week 18
Procedure: radiation therapy
Patients undero radiation therapy in week 19
Experimental: 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 also undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then combination chemotherapy.
 Drug: cyclophosphamide
Given IV
Drug: dexrazoxane hydrochloride
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV
Drug: topotecan hydrochloride
Given IV
Drug: vincristine sulfate
Given IV
Procedure: conventional surgery
Patients undergo surgery in week 18
Procedure: radiation therapy
Patients undero radiation therapy in week 19

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.

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334867

Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Mason Bond, MD Children's & Women's Hospital of British Columbia
Investigator: Leo Mascarenhas, MD Children's Hospital Los Angeles
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00334867     History of Changes
Other Study ID Numbers: CDR0000483611, COG-AEWS0531
Study First Received: June 7, 2006
Last Updated: January 2, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Sarcoma, Ewing's
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
 Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
Etoposide
Razoxane
Vincristine
Topotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2012