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

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

Sponsoren

Hauptsponsor: National Cancer Institute (NCI)

Mitarbeiter: Children's Cancer Group

Quelle National Cancer Institute (NCI)
Kurze Zusammenfassung

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.

detaillierte Beschreibung

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.

Gesamtstatus Completed
Anfangsdatum April 1995
Primäres Abschlussdatum June 2003
Phase Phase 2
Studientyp Interventional
Einschreibung 130
Bedingung
Intervention

Interventionsart: Biological

Interventionsname: filgrastim

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: amifostine trihydrate

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: cyclophosphamide

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: doxorubicin hydrochloride

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: etoposide

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: ifosfamide

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: topotecan hydrochloride

Armgruppenetikett: Arm I

Interventionsart: Drug

Interventionsname: vincristine sulfate

Armgruppenetikett: Arm I

Interventionsart: Procedure

Interventionsname: conventional surgery

Armgruppenetikett: Arm I

Interventionsart: Radiation

Interventionsname: low-LET cobalt-60 gamma ray therapy

Armgruppenetikett: Arm I

Interventionsart: Radiation

Interventionsname: low-LET electron therapy

Armgruppenetikett: Arm I

Interventionsart: Radiation

Interventionsname: low-LET photon therapy

Armgruppenetikett: Arm I

Teilnahmeberechtigung

Kriterien:

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

Geschlecht: All

Mindestalter: N/A

Maximales Alter: 30 Years

Gesunde Freiwillige: No

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

Australia

Canada

Puerto Rico

Switzerland

United States

Überprüfungsdatum

March 2007

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 1
Armgruppe

Etikette: Arm I

Art: Experimental

Beschreibung: See detailed description.

Studiendesign Info

Zuweisung: N/A

Interventionsmodell: Single Group Assignment

Hauptzweck: Treatment

Maskierung: None (Open Label)

Quelle: ClinicalTrials.gov