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

This study has been completed.
Sponsor:
Collaborators:
Southwest Oncology Group
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00006734
First received: December 6, 2000
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Sarcoma
Biological: filgrastim
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: vincristine sulfate
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: brachytherapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Assessed using a two sided log rank test of 0.05.


Enrollment: 587
Study Start Date: May 2001
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A
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.
Biological: filgrastim
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC 614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: ifosfamide
Given IV
Other Names:
  • Ifex
  • NSC #109724
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC #067574
Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: brachytherapy Radiation: radiation therapy
Experimental: Regimen B
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.
Biological: filgrastim
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC 614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: ifosfamide
Given IV
Other Names:
  • Ifex
  • NSC #109724
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC #067574
Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: brachytherapy Radiation: radiation therapy

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.

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006734

  Show 239 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Southwest Oncology Group
Investigators
Study Chair: Richard B. Womer, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00006734     History of Changes
Other Study ID Numbers: AEWS0031, COG-AEWS0031, CDR0000068323, A7983
Study First Received: December 6, 2000
Last Updated: May 16, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Neuroectodermal Tumors
Sarcoma, Ewing
Sarcoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 14, 2014