Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

October 24, 2014 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Randomised Trial Of Single Agent Doxorubicin Versus Doxorubicin Plus Ifosfamide In The First Line Treatment Of Advanced Or Metastatic Soft Tissue Sarcoma

RATIONALE: Drugs used in chemotherapy such as doxorubicin and ifosfamide use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors, such as pegfilgrastim, cause the body to make blood cells. It is not yet known whether doxorubicin alone is more effective with or without ifosfamide and pegfilgrastim in treating soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying giving doxorubicin alone to see how well it works compared to giving doxorubicin together with ifosfamide and pegfilgrastim in treating patients with locally advanced or metastatic soft tissue sarcoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs without ifosfamide and pegfilgrastim as first-line therapy.
  • Compare the response in patients treated with these regimens.
  • Compare the treatment-related mortality of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to WHO performance status (0 vs 1), age group (less than 50 years of age vs 50 years of age and over), presence of liver metastases (yes vs no), histological grade (2 vs 3), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive doxorubicin IV on day 1 (or IV continuously on days 1-3).
  • Arm II: Patients receive doxorubicin IV on days 1-3 and ifosfamide IV over 4 hours on days 1-4. Patients also receive pegfilgrastim subcutaneously on day 5.

In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 4 years.

Study Type

Interventional

Enrollment (Actual)

455

Phase

  • Phase 3

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

  • Austria
      • Graz, Austria, A-8010
        • Karl-Franzens-University Graz
  • Belgium
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Edegem, Belgium, B-2650
        • Universitair Ziekenhuis Antwerpen
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre - Calgary
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute at University of Alberta
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Doctor H. Bliss Murphy Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Margaret and Charles Juravinski Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H3G 1Y6
        • McGill Cancer Centre at McGill University
  • Denmark
      • Aarhus, Denmark, DK-8000
        • Aarhus Universitetshospital - Aarhus Sygehus
      • Copenhagen, Denmark, DK-2730
        • Copenhagen County Herlev University Hospital
  • France
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13385
        • CHU de la Timone
  • Germany
      • Cologne, Germany, D-50924
        • Medizinische Universitaetsklinik I at the University of Cologne
      • Dresden, Germany, D-01307
        • Universitätsklinikum Carl Gustav Carus
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Hannover, Germany, D-30625
        • Medizinische Hochschule Hannover
      • Mannheim, Germany, D-68135
        • Klinikum der Stadt Mannheim
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
      • Groningen, Netherlands, 9700 RB
        • University Medical Center Groningen
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen
      • Rotterdam, Netherlands, 3000 CA
        • University Medical Center Rotterdam at Erasmus Medical Center
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • National Cancer Institute - Bratislava
  • Spain
      • Barcelona, Spain, 08035
        • Vall D'Hebron University Hospital
      • Madrid, Spain, 28040
        • Hospital Universitario San Carlos
  • Switzerland
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
      • London, England, United Kingdom, SW3 6JJ
        • Royal Marsden - London
      • London, England, United Kingdom, WIT 3AA
        • University College of London Hospitals
      • Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
        • Northern Centre for Cancer Treatment at Newcastle General Hospital
      • Plymouth, England, United Kingdom, PL6 8DH
        • Derriford Hospital
      • Sheffield, England, United Kingdom, S1O 2SJ
        • Cancer Research Centre at Weston Park Hospital
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary
      • Edinburgh, Scotland, United Kingdom, EH4 2XU
        • Edinburgh Cancer Centre at Western General Hospital
      • Glasgow, Scotland, United Kingdom, G11 6NT
        • Western Infirmary
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Gartnavel General Hospital

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

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed soft tissue sarcoma

    • Locally advanced unresectable* OR metastatic disease
    • High-grade (grade 2-3) disease according to the FNLCC grading system NOTE: *Disease that could prove resectable (including pulmonary metastasectomy) after a response to chemotherapy is allowed

  • The following tumor types are eligible:

    • Malignant fibrous histiocytoma
    • Myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma
    • Pleomorphic rhabdomyosarcoma
    • Synovial sarcoma
    • Myxofibrosarcoma, intermediate and high-grade
    • Fibrosarcoma
    • Leiomyosarcoma
    • Angiosarcoma
    • Malignant peripheral nerve sheath tumor
    • Epithelioid sarcoma
    • Alveolar rhabdomyosarcoma
    • Unclassifiable sarcoma, not otherwise specified

  • The following tumor types are not eligible:

    • Gastrointestinal stromal tumor
    • Mixed mesodermal tumor
    • Chondrosarcoma
    • Malignant mesothelioma
    • Neuroblastoma
    • Osteosarcoma
    • Ewing's sarcoma/primitive neuroectodermal tumor
    • Desmoplastic small round cell tumor
    • Embryonal rhabdomyosarcoma
    • Alveolar soft part sarcoma

  • Must have a measurable lesion with clinical evidence of progression within the past 6 weeks

    • Osseous lesions and pleural effusions are not considered measurable
  • No known or symptomatic CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 to 60

Performance status

  • WHO 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 1.8 mg/dL
  • Albumin at least 2.5 g/dL

Renal

  • Creatinine no greater than 1.4 mg/dL OR
  • Creatinine clearance greater than 65 mL/min

Cardiovascular

  • No history of cardiovascular disease

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other severe medical illness
  • No psychosis
  • No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up schedule

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for advanced or metastatic disease
  • Prior adjuvant chemotherapy allowed provided there was no disease progression within 6 months after completion of treatment

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the sole index lesion

Surgery

  • Not specified

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: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Toxicity as assessed by CTC 2.0
Response as assessed by RECIST criteria
Treatment-related mortality

Collaborators and Investigators

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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Ian R. Judson, MA, MD, FRCP, Institute of Cancer Research, United Kingdom

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, 2003

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

June 5, 2003

First Submitted That Met QC Criteria

June 5, 2003

First Posted (Estimate)

June 6, 2003

Study Record Updates

Last Update Posted (Estimate)

October 27, 2014

Last Update Submitted That Met QC Criteria

October 24, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-62012

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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