INTENSIVE THERAPY WITH GROWTH FACTOR SUPPORT FOR PATIENTS WITH EWING'S TUMOR METASTATIC AT DIAGNOSIS: A PEDIATRIC ONCOLOGY GROUP PHASE II STUDY
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
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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Mark L. Bernstein, MD, FRCPC
Montreal Children's Hospital at McGill University Health Center
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Kaplan Cancer Center||New York, New York 10016|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|
|Lineberger Comprehensive Cancer Center, UNC||Chapel Hill, North Carolina 27599-7295|
|Ireland Cancer Center||Cleveland, Ohio 44106-5065|
|Cancer Center, University of Virginia HSC||Charlottesville, Virginia 22908|
|MBCCOP - LSU Medical Center||New Orleans, Louisiana 70112|
|Memorial Mission Hospital||Asheville, North Carolina 28801|
|Medical City Dallas Hospital||Dallas, Texas 75230|
|San Antonio Military Pediatric Cancer and Blood Disorders Center||Lackland Air Force Base, Texas 78236-5300|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|CCOP - Kalamazoo||Kalamazoo, Michigan 49007-3731|
|Vanderbilt Cancer Center||Nashville, Tennessee 37232-6838|
|CCOP - Merit Care Hospital||Fargo, North Dakota 58122|
|Huntsman Cancer Institute||Salt Lake City, Utah 84112|
|David Grant Medical Center||Travis Air Force Base, California 94535|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Herbert Irving Comprehensive Cancer Center||New York, New York 10032|
|Veterans Affairs Medical Center - Fargo||Fargo, North Dakota 58102|
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Long Beach Memorial Medical Center||Long Beach, California 90806|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's Hospital of Denver||Denver, Colorado 80218|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital Medical Center - Cincinnati||Cincinnati, Ohio 45229-3039|
|Children's Hospital of Columbus||Columbus, Ohio 43205-2696|
|Doernbecher Children's Hospital||Portland, Oregon 97201-3098|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Via Christi Regional Medical Center-Saint Francis Campus||Wichita, Kansas 67214|
|Children's Mercy Hospital - Kansas City||Kansas City, Missouri 64108|