RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving chemotherapy after surgery is more effective than surgery alone in treating soft tissue sarcoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without chemotherapy in treating patients who have soft tissue sarcoma.

Condition	Treatment or Intervention	Phase
adult soft tissue sarcoma clear cell sarcoma of the kidney ovarian sarcoma Pheochromocytoma uterine sarcoma	Drug: doxorubicin  Drug: filgrastim  Drug: ifosfamide  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: isolated perfusion  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the local disease control, overall survival, and relapse-free survival in patients with high-grade soft tissue sarcoma treated with adjuvant high-dose doxorubicin and ifosfamide plus filgrastim (G-CSF) vs no adjuvant chemotherapy and G-CSF after definitive surgery.
• Compare the toxicity and morbidity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, site of primary tumor (extremity vs trunk, including shoulder, pelvic girdle, head, or neck vs central, including intrathoracic, visceral, uterine, or retroperitoneal), size of primary tumor (less than 5 cm vs 5 cm or greater in largest diameter), postoperative radiotherapy (yes vs no), and isolated limb perfusion therapy (yes vs no).

Some patients undergo isolated limb perfusion therapy with cytotoxics and/or cytokines.

No more than 8 weeks after biopsy or inadequate surgery, patients undergo definitive surgery. Patients with complete resection undergo radiotherapy assessment and then randomization. Patients with incomplete or marginal resection (except for central lesions) undergo re-excision and, in the absence of macroscopic disease, assessment for postoperative radiotherapy followed by randomization.

• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive no adjuvant chemotherapy or filgrastim (G-CSF). Beginning within 6 weeks after surgery, eligible patients undergo radiotherapy as outlined below.
• Arm II: Beginning within 4 weeks after surgery, patients receive high-dose doxorubicin IV over 20 minutes followed by ifosfamide IV over 24 hours and G-CSF subcutaneously daily beginning 24 hours after completion of ifosfamide infusion and continuing for 10 days. Treatment continues every 3 weeks for 5 courses. Beginning within 6 weeks after completion of chemotherapy, eligible patients undergo radiotherapy as outlined below.
• Radiotherapy: Patients with incomplete or marginal resection undergo radiotherapy 5 days a week for 6-6.6 weeks. Patients with complete microscopic resection undergo radiotherapy 5 days a week for 5 weeks followed by boost radiotherapy 5 days a week for 1 week. Patients are followed every 2 months for 1 year, every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 3.5 years.

Ages Eligible for Study:  16 Years   -   69 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven soft tissue sarcoma that is amenable to definitive surgery no more than 8 weeks after biopsy or inadequate surgery
• Eligible subtypes:
• Alveolar soft part sarcoma
• Angiosarcoma
• Fibrosarcoma
• Leiomyosarcoma
• Malignant fibrous histiocytoma
• Liposarcoma (round cell and pleomorphic)
• Miscellaneous sarcoma (including pelvic mixed mesodermal tumors)
• Malignant paraganglioma
• Neurogenic sarcoma
• Rhabdomyosarcoma
• Synovial sarcoma
• Unclassifiable sarcoma
• Ineligible subtypes:
• Chondrosarcoma
• Dermatofibrosarcoma
• Embryonal rhabdomyosarcoma
• Ewing's sarcoma
• Kaposi's sarcoma
• Liposarcoma (myxoid and well differentiated)
• Malignant mesothelioma
• Neuroblastoma
• Osteosarcoma
• Confirmed high-grade tumor (i.e., Trojani Grade II or III)
• No metastases on staging with chest x-ray and thoracic CT scan
• No regional lymph node involvement
• Locally recurrent disease allowed
• Interval of 3 months or more between definitive surgery and recurrence

PATIENT CHARACTERISTICS: Age:

• 16 to 69

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Platelet count greater than 120,000/mm^3
• No bleeding disorders

Hepatic:

• Bilirubin no greater than 1.25 times normal
• No severe hepatic dysfunction

Renal:

• Creatinine less than 1.6 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No clear history of angina
• No documented myocardial infarction
• No existing cardiac failure

Other:

• No serious infection
• No other malignancy except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to affected area

Surgery:

• See Disease Characteristics

Austria
      Karl-Franzens-University Graz, Graz,  A-8010,  Austria
Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency - Vancouver Island Cancer Centre, Victoria,  British Columbia,  V8R 6V5,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Ontario
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
Canada, Quebec
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Denmark
      Aarhus Kommunehospital, Aarhus,  DK-8000,  Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark
France
      Centre Leon Berard, Lyon,  69373,  France
      CHU de la Timone, Marseille,  13385,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany
      Klinikum Grosshadern, Munich,  D-81377,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Universitaetsklinikum Essen, ESSEN,  D-45122,  Germany
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany
Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands
      Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands
      Daniel Den Hoed Cancer Center at Erasmus University Medical Center, Rotterdam,  3075 EA,  Netherlands
Portugal
      Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa, Lisbon,  1099-023 Codex,  Portugal
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
Spain
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonsspital - St. Gallen, St. Gallen,  CH-9007,  Switzerland
United Kingdom, England
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom
      Middlesex Hospital- Meyerstein Institute, London,  England,  WIT 3AA,  United Kingdom
      Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom
      Royal Devon and Exeter Hospital, Exeter,  England,  EX2 5DW,  United Kingdom
      Royal Marsden NHS Trust - London, London,  England,  SW3 6JJ,  United Kingdom
      St. James's Hospital, Leeds,  England,  LS9 7TF,  United Kingdom
      Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom

Study chairs or principal investigators

Penella Woll, MD, PhD,  Weston Park Hospital   
Vivien H.C. Bramwell, MB, BS, PhD, FRCP,  Study Chair,  Tom Baker Cancer Center - Calgary   

Study ID Numbers:  CDR0000064132; EORTC-62931; CAN-NCIC-SR3
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002641
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08