RATIONALE: STI571 may interfere with the growth of tumor cells and may be an effective treatment for cancer. It is not yet known which dose of STI571 is more effective in treating gastrointestinal stromal tumors. PURPOSE: Randomized phase III trial to compare the effectiveness of two different doses of STI571 in treating patients who have metastatic or unresectable gastrointestinal stromal tumor.

Condition	Treatment or Intervention	Phase
gastrointestinal stromal tumor	Procedure: protein tyrosine kinase inhibitor therapy  Procedure: enzyme inhibitor therapy  Drug: imatinib mesylate	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the overall and progression-free survival of patients with CD117- expressing metastatic or unresectable gastrointestinal stromal tumor treated with two different doses of STI571. II. Compare the confirmed, unconfirmed, complete, and partial response rates in patients treated with these regimens. III. Compare the toxic effects of these regimens in these patients.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified according to Zubrod performance status (0-2 vs 3) and measurable disease (yes vs no). Patients are randomized to one of two treatment arms. Arm I: Patients receive oral STI571 once daily. Arm II: Patients receive oral STI571 twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients in arm I with progressive disease may cross over to arm II and receive treatment in the absence of further disease progression. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 24 months.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed gastrointestinal stromal tumor; Distantly metastatic or unresectable disease; Visceral or intra-abdominal primary disease; Immunohistochemical documentation of CD117 expression
• No known brain metastasis

--Prior/Concurrent Therapy--

• Biologic therapy: At least 28 days since prior biologic therapy and recovered; No concurrent anti-cancer biologic therapy
• Chemotherapy: At least 28 days since prior chemotherapy and recovered; No concurrent chemotherapy
• Endocrine therapy: Recovered from prior endocrine therapy
• Radiotherapy: Recovered from prior radiotherapy; No concurrent radiotherapy
• Surgery: At least 14 days since prior major surgery and recovered
• Other: At least 28 days since prior investigational drug and recovered; No concurrent therapeutic anticoagulation with warfarin; Concurrent mini-dose oral warfarin (1 mg/day) allowed as prophylaxis for central venous catheter thrombosis; Concurrent therapeutic anticoagulation with low-molecular weight heparin (e.g., enoxaparin) or other agents allowed; No other concurrent investigational drugs

--Patient Characteristics--

• Age: 15 and over
• Performance status: Zubrod 0-3
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,000/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL (transfusion allowed)
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); SGOT or SGPT no greater than 2.5 times ULN (5 times ULN if liver metastases present); No uncontrolled chronic liver disease
• Renal: Creatinine no greater than 1.5 times ULN; No uncontrolled chronic renal disease
• Cardiovascular: No New York Heart Association class III or IV heart disease; No congestive heart failure; No myocardial infarction within the past 2 months
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective barrier contraception during and for up to 3 months after study; No other severe and/or uncontrolled medical disease; No uncontrolled diabetes; No active uncontrolled infection (e.g., HIV); No medical or psychological condition that would preclude study; No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer in complete remission

Australia, Victoria
      Peter MacCallum Cancer Institute, East Melbourne,  Victoria,  8006,  Australia
Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
Denmark
      Aarhus Kommunehospital, Aarhus,  DK-8000,  Denmark
      Herlev Hospital - University Hospital of Copenhagen, Copenhagen,  DK-2730,  Denmark
France
      Centre Leon Berard, Lyon,  69373,  France
      CHU de la Timone, Marseille,  13385,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Klinikum Grosshadern, Munich,  D-81377,  Germany
      Medizinische Hochschule Hannover, Hannover,  D-30625,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Universitats-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany
Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan,  20133,  Italy
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-6500 HB,  Netherlands
New Zealand
      Wellington Cancer Centre, Wellington,  6039,  New Zealand
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
Spain
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain
      Hospital General de Asturias, Oviedo,  33006,  Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
      Instituto Valenciano De Oncologia, Valencia,  46009,  Spain
Sweden
      Lund University Hospital, Lund,  S-22185,  Sweden
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  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
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  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
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom
United Kingdom, Wales
      Velindre Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom

Study chairs or principal investigators

Richard L. Schilsky,  Study Chair,  Cancer and Leukemia Group B   
Charles A. Coltman, Jr.,  Study Chair
Robert L. Comis,  Study Chair
Vivien H.C. Bramwell,  Study Chair
Jacob Verweij,  Study Chair
P. G. Casali,  Study Chair
Kirsten Sundby Hall,  Study Chair
John Raymond Zalcberg,  Study Chair

Study ID Numbers:  CDR0000068422; CLB-80004; INT-S0033
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  February 2, 2001
ClinicalTrials.gov Identifier:  NCT00009906
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08