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 ifosfamide or doxorubicin is more effective for advanced or metastatic soft tissue sarcoma. PURPOSE: Randomized phase III trial to compare the effectiveness of ifosfamide with that of doxorubicin in treating patients who have advanced or metastatic soft tissue sarcoma.

Condition	Treatment or Intervention	Phase
Soft Tissue Sarcoma Uterine Cancer	Drug: doxorubicin  Drug: ifosfamide	Phase III

Further Study Details: 

OBJECTIVES: I. Determine the progression free survival rate in patients with advanced or metastatic soft tissue sarcoma treated with either of two different regimens of ifosfamide or doxorubicin. II. Assess the toxic effects of these therapies and response rate in these patients.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized into one of 3 arms (continuous ifosfamide, ifosfamide daily for 3 days, or doxorubicin). Patients are stratified by performance status (0 vs 1), liver involvement (no vs yes), histological type (leiomyosarcoma vs synovial sarcoma vs other), and histological grade (1 vs 2 vs 3). Arm I: Patients receive doxorubicin by bolus infusion for 5-20 minutes once every 3 weeks. Arm II: Patients receive ifosfamide by intravenous infusion for 4 hours on days 1, 2, and 3 every three weeks. Arm III: Patients receive ifosfamide by intravenous infusion for 72 hours every 3 weeks. Patients are assessed after every 2 courses of therapy. Each course of therapy consists of 3 weeks of treatment. Patients may receive a maximum of 6 courses of therapy in the absence of toxicity and disease progression. Patients are followed every 12 weeks for survival.

PROJECTED ACCRUAL: A total of 780 patients (260 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  15 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histolgically proven advanced or metastatic soft tissue sarcoma including the following: Malignant fibrous histiocytoma; Liposarcoma; Rhabdomyosarcoma; Synovial sarcoma; Malignant paraganglioma; Fibrosarcoma; Leiomyosarcoma; Angiosarcoma including haemangiopericytoma; Neurogenic sarcoma; Unclassified sarcoma; Mixed mesodermal tumor of the uterus
• Measurable disease with evidence of progression in prior 6 weeks
• No symptomatic or known CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No radiotherapy to the sole index lesion
• Surgery: Not specified

--Patient Characteristics--

• Age: 15 to 65
• Performance status: WHO 0-1
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3000/mm3; Neutrophil count greater than 2,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater 1.75 mg/dL; Albumin at least 25 g/L
• Renal: Creatinine clearance greater than 70 mL/min
• Cardiovascular: No history of uncontrolled cardiovascular disease
• Other: Fertile women must use effective contraception; No other severe medical illness including psychosis; No prior primary malignant tumor except: Adequately treated carcinoma in situ of the cervix; Basal cell carcinoma

Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Denmark
      Aarhus Kommunehospital, Aarhus,  DK-8000,  Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark
France
      Centre Leon Berard, Lyon,  69373,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Klinikum Grosshadern, Munich,  D-81377,  Germany
      Medizinische Hochschule Hannover, Hannover,  D-30625,  Germany
Hungary
      National Institute of Oncology, Budapest,  1125,  Hungary
Netherlands
      Antoni van Leeuwenhoekhuis, Amsterdam,  1066 CX,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Rotterdam Cancer Institute, Rotterdam,  3075 EA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6252 HB,  Netherlands
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
Spain
      Hospital Insular de Gran Canaria, Las Palmas,  G.C.,  Spain
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 Marsden NHS Trust, 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

Paul C. Lorigan,  Study Chair,  EORTC Soft Tissue and Bone Sarcoma Cooperative Group   

Study ID Numbers:  CDR0000066070; EORTC-62971
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003212
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08