Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	50 and under at diagnosis	NCI	COG-AEWS0031 CCG-A7983, AEWS0031, NCT00006734, SWOG-COG-AEWS0031

Objectives

1. 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.

Entry 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

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

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

Expected Enrollment

Approximately 528 patients will be accrued for this study within 4-5 years.

Outcomes

Event-free survival

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.

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Richard Womer, MD, Protocol chair		Ph: 215-590-2229 Email: rwomer@mail.med.upenn.edu

Southwest Oncology Group

Karen Albritton, MD, Study coordinator		Ph: 617-632-2545; 866-790-4500 Email: karen_albritton@dfci.harvard.edu

Registry Information
Official Title		Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors
Trial Start Date		2001-05-07
Registered in ClinicalTrials.gov		NCT00006734
Date Submitted to PDQ		2000-10-06
Information Last Verified		2005-10-26
NCI Grant/Contract Number		CA13539

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