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

January 31, 2013 updated by: National Cancer Institute (NCI)

INTENSIVE THERAPY WITH GROWTH FACTOR SUPPORT FOR PATIENTS WITH EWING'S TUMOR METASTATIC AT DIAGNOSIS: A PEDIATRIC ONCOLOGY GROUP PHASE II STUDY

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • British Columbia Children's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3J 3G9
        • IWK Grace Health Centre
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • University of Puerto Rico School of Medicine Medical Sciences Campus
  • Switzerland
      • Geneva, Switzerland, 1211
        • Clinique de Pediatrie
  • United States
    • California
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92668
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94115-0128
        • UCSF Cancer Center and Cancer Research Institute
      • Travis Air Force Base, California, United States, 94535
        • David Grant Medical Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Children's Hospital of Denver
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Cancer Research Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5265
        • Indiana University Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center-Saint Francis Campus
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0752
        • University Of Michigan Comprehensive Cancer Center
      • Kalamazoo, Michigan, United States, 49007-3731
        • CCOP - Kalamazoo
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital - Kansas City
    • Nebraska
      • Omaha, Nebraska, United States, 68198-3330
        • University of Nebraska Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute Of New Jersey
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • Kaplan Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Memorial Mission Hospital
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center, UNC
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Veterans Affairs Medical Center - Fargo
      • Fargo, North Dakota, United States, 58122
        • CCOP - Merit Care Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Children's Hospital Medical Center - Cincinnati
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center
      • Columbus, Ohio, United States, 43205-2696
        • Children's Hospital of Columbus
    • Oregon
      • Portland, Oregon, United States, 97201-3098
        • Doernbecher Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt Cancer Center
    • Texas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Houston, Texas, United States, 77030
        • University of Texas - MD Anderson Cancer Center
      • Lackland Air Force Base, Texas, United States, 78236-5300
        • San Antonio Military Pediatric Cancer and Blood Disorders Center
      • San Antonio, Texas, United States, 78284
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Huntsman Cancer Institute
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Cancer Center, University of Virginia HSC
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
See detailed description.
Drug: cyclophosphamide
Drug: amifostine trihydrate
Drug: etoposide
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Procedure: conventional surgery
Biological: filgrastim
Drug: topotecan hydrochloride
Drug: ifosfamide
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Radiation: low-LET cobalt-60 gamma ray therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Collaborators

Children's Cancer Group

Investigators

  • Study Chair: Mark L. Bernstein, MD, FRCPC, Montreal Children's Hospital at McGill University Health Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1995

Primary Completion (Actual)

June 1, 2003

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

June 17, 2003

First Posted (Estimate)

June 18, 2003

Study Record Updates

Last Update Posted (Estimate)

February 1, 2013

Last Update Submitted That Met QC Criteria

January 31, 2013

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01832
  • POG-9457
  • CCG-P9457
  • CDR0000064137 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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