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Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor

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ClinicalTrials.gov Identifier: NCT00002643
Recruitment Status : Completed
First Posted : June 18, 2003
Last Update Posted : February 1, 2013
Sponsor:
Collaborator:
Children's Cancer Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE June 18, 2003
Last Update Posted Date February 1, 2013
Study Start Date  ICMJE April 1995
Actual Primary Completion Date June 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor
Official Title  ICMJE INTENSIVE THERAPY WITH GROWTH FACTOR SUPPORT FOR PATIENTS WITH EWING'S TUMOR METASTATIC AT DIAGNOSIS: A PEDIATRIC ONCOLOGY GROUP PHASE II STUDY
Brief Summary Phase II trial to study the effectiveness of combination chemotherapy in treating patients with newly diagnosed metastatic Ewing's sarcoma or primitive neuroectodermal tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
Detailed Description

OBJECTIVES:

I. Evaluate the response rate and duration of response of patients with newly diagnosed, metastatic Ewing's sarcoma or primitive neuroectodermal tumor treated with maximally intensified VAdrC (vincristine, doxorubicin, cyclophosphamide) alternating with IE (ifosfamide, etoposide).

II. Evaluate the response to new agents (first topotecan, then topotecan with cyclophosphamide) utilized in an upfront treatment window.

III. Assess the role of surgery with regard to local control of primary and metastatic sites and disease course.

IV. Evaluate whether individual variability in ifosfamide and cyclophosphamide metabolism correlates with toxicity and/or response.

V. Evaluate the rise in the absolute neutrophil count following one dose of filgrastim (G-CSF) given immediately prior to a chemotherapy course as an indicator of bone marrow reserve and subsequent myelosuppression.

VI. Determine if amifostine provides significant chemo-radio protection, particularly against the cumulative toxicities of this intensive therapy.

OUTLINE: This is a partially randomized, multicenter study.

Patients are treated on the investigational window first or proceed to induction therapy immediately, if aggressive treatment is necessary.

INVESTIGATIONAL WINDOW: Patients receive cyclophosphamide IV and topotecan IV over 30 minutes on days 1-5. Filgrastim (G-CSF) is administered subcutaneously (SQ) beginning day 6 until blood cell counts recover. Treatment is repeated at week 3.

INDUCTION THERAPY: Patients over 12 months old are randomized to receive amifostine or not. Patients receive etoposide IV over 45 minutes and ifosfamide IV over 2 hours on days 1-5. Amifostine IV over 15 minutes is also administered prior to ifosfamide. Patients receive G-CSF SQ (or IV over 2 hours) beginning on day 6. This course of treatment is administered on weeks 6, 12, and 18. Patients receive the VAdrC chemotherapy regimen on weeks 9 and 15. This regimen consists of vincristine IV and amifostine IV over 15 minutes on days 1, 8, and 15, cyclophosphamide IV over 30 minutes and doxorubicin IV over 48 hours on days 1 and 2, and G-CSF beginning on day 3. The VAdrC regimen is continued during local therapy on weeks 21-29 and 39-47, except the day 15 dose of vincristine is omitted, cyclophosphamide is administered on day 1 only on weeks 21, 24, 27, 39, 42, and 45, and doxorubicin is replaced with etoposide IV over 60 minutes on days 1-3 on weeks 24, 28, 42, and 45. Local therapy begins after 21 weeks of chemotherapy. Patients who respond to chemotherapy and have resectable disease undergo a complete resection with negative margins. Patients with unresectable disease or bulky lesions undergo radiotherapy. Some patients may undergo both surgery and radiotherapy. Local therapy of metastases is delayed until after week 39. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neutropenia
  • Sarcoma
Intervention  ICMJE
  • Biological: filgrastim
  • Drug: amifostine trihydrate
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: ifosfamide
  • Drug: topotecan hydrochloride
  • Drug: vincristine sulfate
  • Procedure: conventional surgery
  • Radiation: low-LET cobalt-60 gamma ray therapy
  • Radiation: low-LET electron therapy
  • Radiation: low-LET photon therapy
Study Arms  ICMJE Experimental: Arm I
See detailed description.
Interventions:
  • Biological: filgrastim
  • Drug: amifostine trihydrate
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: ifosfamide
  • Drug: topotecan hydrochloride
  • Drug: vincristine sulfate
  • Procedure: conventional surgery
  • Radiation: low-LET cobalt-60 gamma ray therapy
  • Radiation: low-LET electron therapy
  • Radiation: low-LET photon therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January¬†31,¬†2013)
130
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Newly diagnosed, pathologically confirmed Ewing's sarcoma or primitive neuroectodermal tumor (PNET)
  • Diagnosis established from biopsy of primary tumor Light microscopy (hematoxylin and eosin stained) consistent with Ewing's sarcoma or PNET
  • No immunohistochemical or ultrastructural characteristics inconsistent with Ewing's sarcoma or PNET or suggestive of rhabdomyosarcoma
  • Metastatic disease required
  • Biopsy of radiographically questionable metastases (e.g., pulmonary lesions) required
  • Chest wall tumor with separate pleural mass considered metastatic
  • No positive pleural fluid cytology alone

PATIENT CHARACTERISTICS:

  • Age: 30 and under
  • Absolute neutrophil count greater than 1,200/mm3
  • Platelet count greater than 120,000/mm3
  • Bilirubin less than 1.5 mg/dL
  • AST/ALT less than 3 times normal
  • Creatinine normal for age
  • Significant renal abnormality/disease eligible only if nuclear GFR is normal and study coordinator approves
  • Echocardiogram or MUGA normal

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy
  • Resection at diagnosis is discouraged but does not exclude
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Puerto Rico,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00002643
Other Study ID Numbers  ICMJE NCI-2012-01832
POG-9457
CCG-P9457
CDR0000064137 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Children's Cancer Group
Investigators  ICMJE
Study Chair: Mark L. Bernstein, MD, FRCPC Montreal Children's Hospital at McGill University Health Center
Study Chair: Paul A. Meyers, MD Memorial Sloan Kettering Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date March 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP