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.

Condition	Treatment or Intervention	Phase
adult soft tissue sarcoma	Drug: doxorubicin  Drug: ifosfamide  Drug: pegfilgrastim  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: combination therapy  Procedure: cytokine therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

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

Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
Denmark
      Aarhus University Hospital - Aarhus Sygehus - Norrebrogade, Aarhus,  DK-8000,  Denmark; Recruiting
      Herlev Hospital - University Hospital of Copenhagen, Copenhagen,  DK-2730,  Denmark; Recruiting
France
      Centre Leon Berard, Lyon,  69373,  France; Recruiting
      CHU de la Timone, Marseille,  13385,  France; Recruiting
      Institut Bergonie, Bordeaux,  33076,  France; Recruiting
Germany
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany; Recruiting
      Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen, Munich,  D-81377,  Germany; Recruiting
Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting
      University Medical Center Groningen, Groningen,  9700 RB,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
      University Medical Center Rotterdam at Erasmus Medical Center, Rotterdam,  3000 CA,  Netherlands; Recruiting
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia; Recruiting
Spain
      Hospital General Universitari Vall d'Hebron, Barcelona,  08035,  Spain; Recruiting
      Hospital Universitario San Carlos, Madrid,  28040,  Spain; Recruiting
United Kingdom, England
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Derriford Hospital, Plymouth,  England,  PL6 8DH,  United Kingdom; Recruiting
      Meyerstein Institute of Oncology at University College of London Hospitals, London,  England,  WIT 3AA,  United Kingdom; Recruiting
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2TH,  United Kingdom; Recruiting
      Royal Marsden NHS FoundationTrust - London, London,  England,  SW3 6JJ,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom; Recruiting
      Western Infirmary, Glasgow,  Scotland,  G11 6NT,  United Kingdom; Recruiting

Study chairs or principal investigators

Ian Robert Judson, MA, MD, FRCP,  National Cancer Research Institute (NCRI)   

Study ID Numbers:  CDR0000302584; EORTC-62012; NCT00061984
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00061984
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08