RATIONALE: STI571 may interfere with the growth of cancer cells and may be an effective treatment for soft tissue sarcoma. PURPOSE: Phase I/II trial to study the effectiveness of STI571 in treating patients who have recurrent or refractory soft tissue sarcoma.

Condition	Treatment or Intervention	Phase
stage/cell type, small intestine cancer cellular diagnosis, adult soft tissue sarcoma cellular diagnosis, uterine sarcoma Cancer Gastrointestinal Cancer stage, adult soft tissue sarcoma adult soft tissue sarcoma musculoskeletal cancer body system/site cancer female reproductive cancer small intestine cancer uterine sarcoma stage, uterine sarcoma adult solid tumor solid tumor Muscle Cancer	Drug: STI571	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose and associated toxicity of STI571 in patients with refractory or recurrent soft tissue sarcoma. II. Determine the pharmacokinetic profile of this treatment regimen in these patients. III. Determine the objective response and duration of response in these patients with this treatment regimen.

PROTOCOL OUTLINE: This is a dose escalation and dose efficacy, multicenter study. In the dose efficacy portion, patients are stratified according to disease type (gastrointestinal stromal tumor vs all other soft tissue sarcomas). Phase I: Patients receive oral STI571 daily for a maximum of 24 months in the absence of disease progression or unacceptable toxicity. Cohorts of 3-8 patients receive escalating doses of STI571 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6-8 patients experience dose limiting toxicities. The recommended phase II dose is defined as the dose preceding the MTD. Phase II: Patients receive the recommended phase II dose of STI571 as in phase I. Patients are followed every 8 weeks until disease progression, and then every 16 weeks thereafter.

PROJECTED ACCRUAL: Approximately 47-72 patients (7-32 in phase I and 40 in phase II) will be accrued for this study.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed soft tissue sarcoma; Malignant fibrous histiocytoma; Liposarcoma; Rhabdomyosarcoma; Synovial sarcoma; Malignant paraganglioma; Fibrosarcoma; Leiomyosarcoma; Angiosarcoma; Hemangiopericytoma; Neurogenic sarcoma; Unclassified sarcoma; Miscellaneous sarcoma (including mixed mesodermal tumors of the uterus); Gastrointestinal stromal tumor (GIST) (must be c-kit positive)
• No malignant mesothelioma, chondrosarcoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, or embryonal rhabdomyosarcoma
• Phase I study and nonGIST phase II study patients: Must have received one prior first line combination chemotherapy regimen or two first line single agent regimens; Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment
• Phase II GIST patients: No more than one prior first line combination chemotherapy regimen or two first line single agent regimens; Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment
• Measurable disease with evidence of progression in past 6 weeks; Osseous lesions and pleural effusions not considered measurable
• No symptomatic or known CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; At least 4 weeks since prior chemotherapy; No other concurrent local or systemic chemotherapy
• Endocrine therapy: No concurrent systemic corticosteroid therapy
• Radiotherapy: No prior radiotherapy to sole index lesion; Concurrent radiotherapy to any lesion allowed if not the sole target lesion
• Surgery: Not specified
• Other: No prior embolization to sole index lesion; No other concurrent investigational drug; No concurrent warfarin

--Patient Characteristics--

• Age: 15 and over
• Performance status: WHO 0-1
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.8 mg/dL; Albumin at least 25 g/L
• Renal: Creatinine no greater than 1.4 mg/dL OR Creatinine clearance greater than 65 mL/min
• Cardiovascular: No history of cardiovascular disease
• Other: No prior or concurrent second primary malignant tumors except adequately treated carcinoma in situ of the cervix or basal cell carcinoma; No other severe illness (including psychosis); Not pregnant; Fertile patients must use effective contraception during and for 6 months following study

Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Denmark
      Aarhus Kommunehospital, Aarhus,  DK-8000,  Denmark
      Herlev Hospital - University Hospital of Copenhagen, Herlev,  DK-2730,  Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark
France
      Centre Leon Berard, Lyon,  69373,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  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
United Kingdom, England
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom
      Royal Marsden NHS Trust, London,  England,  SW3 6JJ,  United Kingdom
      Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom

Study chairs or principal investigators

Jacob Verweij,  Study Chair,  EORTC Soft Tissue and Bone Sarcoma Cooperative Group   

Study ID Numbers:  CDR0000068226; EORTC-62001-16003; NOVARTIS-CSTI5710203
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006357
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08