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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002643
• Other study ID #: NCI-2012-01832
• Secondary ID: POG-9457CCG-P945
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: January 31, 2013
• Start date: April 1995

Study information

• Verified date: March 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. primary completion date: June 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neutropenia
• Sarcoma

Intervention

Biological:
• filgrastim

Drug:
• amifostine trihydrate

• cyclophosphamide

• doxorubicin hydrochloride

• etoposide

• ifosfamide

• topotecan hydrochloride

• vincristine sulfate

Procedure:
• conventional surgery

Radiation:
• low-LET cobalt-60 gamma ray therapy

• low-LET electron therapy

• low-LET photon therapy

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	IWK Grace Health Centre	Halifax	Nova Scotia
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Puerto Rico	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan
Switzerland	Clinique de Pediatrie	Geneva
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Memorial Mission Hospital	Asheville	North Carolina
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Cancer Center, University of Virginia HSC	Charlottesville	Virginia
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Children's Hospital of Denver	Denver	Colorado
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital - Kansas City	Kansas City	Missouri
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Kaplan Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Children's National Medical Center	Washington	District of Columbia
United States	Via Christi Regional Medical Center-Saint Francis Campus	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Children's Cancer Group

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico,  Switzerland, 

References & Publications (3)

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 Oncolo — View Citation

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. — View Citation

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 — View Citation