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

NCT ID: NCT00002643

Last Updated: 2013-02-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-04-30

Brief Summary

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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

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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.

Conditions

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Neutropenia Sarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

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Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

amifostine trihydrate

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

topotecan hydrochloride

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Interventions

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filgrastim

Intervention Type BIOLOGICAL

amifostine trihydrate

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

topotecan hydrochloride

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Echocardiogram or MUGA normal

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy or radiotherapy
* Resection at diagnosis is discouraged but does not exclude
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Cancer Group

OTHER

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark L. Bernstein, MD, FRCPC

Role: STUDY_CHAIR

Montreal Children's Hospital at McGill University Health Center

Paul A. Meyers, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

David Grant Medical Center

Travis Air Force Base, California, United States

Site Status

Children's Hospital of Denver

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Via Christi Regional Medical Center-Saint Francis Campus

Wichita, Kansas, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Kaplan Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Mission Hospital

Asheville, North Carolina, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Fargo

Fargo, North Dakota, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

San Antonio Military Pediatric Cancer and Blood Disorders Center

Lackland Air Force Base, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Cancer Center, University of Virginia HSC

Charlottesville, Virginia, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Grace Health Centre

Halifax, Nova Scotia, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

University of Puerto Rico School of Medicine Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Clinique de Pediatrie

Geneva, , Switzerland

Site Status

Countries

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United States Australia Canada Puerto Rico Switzerland

References

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Souid AK, Fahey RC, Dubowy RL, Newton GL, Bernstein ML. WR-2721 (amifostine) infusion in patients with Ewing's sarcoma receiving ifosfamide and cyclophosphamide with mesna: drug and thiol levels in plasma and blood cells, a Pediatric Oncology Group study. Cancer Chemother Pharmacol. 1999;44(6):498-504. doi: 10.1007/s002800051124.

Reference Type BACKGROUND
PMID: 10550571 (View on PubMed)

Bernstein ML, Devidas M, Lafreniere D, Souid AK, Meyers PA, Gebhardt M, Stine K, Nicholas R, Perlman EJ, Dubowy R, Wainer IW, Dickman PS, Link MP, Goorin A, Grier HE; Pediatric Oncology Group; Children's Cancer Group Phase II Study 9457; Children's Oncology Group. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. J Clin Oncol. 2006 Jan 1;24(1):152-9. doi: 10.1200/JCO.2005.02.1717.

Reference Type RESULT
PMID: 16382125 (View on PubMed)

Souid AK, Newton GL, Dubowy RL, Fahey RC, Bernstein ML. Determination of the cytoprotective agent WR-2721 (Amifostine, Ethyol) and its metabolites in human blood using monobromobimane fluorescent labeling and high-performance liquid chromatography. Cancer Chemother Pharmacol. 1998;42(5):400-6. doi: 10.1007/s002800050836.

Reference Type RESULT
PMID: 9771955 (View on PubMed)

Other Identifiers

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POG-9457

Identifier Type: -

Identifier Source: secondary_id

CCG-P9457

Identifier Type: -

Identifier Source: secondary_id

CDR0000064137

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01832

Identifier Type: -

Identifier Source: org_study_id

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