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Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
This study is ongoing, but not recruiting participants.
First Received: February 2, 2001   Last Updated: February 13, 2009   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborators: National Cancer Institute (NCI)
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00009906
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: Phase III Randomized, Intergroup Trial Assessing The Clinical Activity Of STI-571 At Two Dose Levels In Patients With Unresectable Or Metastatic Gastrointestinal Stromal Tumors (GIST) Expressing The KIT Receptor Tyrosine Kinase (CD117)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 2000
Detailed Description:

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 imatinib mesylate. 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.

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 imatinib mesylate once daily. Arm II: Patients receive oral imatinib mesylate 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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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 participation 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 participation 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

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00009906

  Hide Study Locations
Locations
Australia, Victoria
Peter MacCallum Cancer Institute
East Melbourne, Victoria, Australia, 8006
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Canada, Ontario
Cancer Care Ontario-London Regional Cancer Centre
London, Ontario, Canada, N6A 4L6
Denmark
Aarhus Kommunehospital
Aarhus, Denmark, DK-8000
Herlev Hospital - University Hospital of Copenhagen
Copenhagen, Denmark, DK-2730
France
Centre Leon Berard
Lyon, France, 69373
CHU de la Timone
Marseille, France, 13385
Institut Gustave Roussy
Villejuif, France, F-94805
Germany
Klinikum Grosshadern
Munich, Germany, D-81377
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Robert Roessle Klinik
Berlin, Germany, D-13122
Universitats-Krankenhaus Eppendorf
Hamburg, Germany, D-20246
Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori
Milan, Italy, 20133
Netherlands
Academisch Ziekenhuis Groningen
Groningen, Netherlands, 9713 EZ
Antoni van Leeuwenhoekhuis
Amsterdam, Netherlands, 1066 CX
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Rotterdam Cancer Institute
Rotterdam, Netherlands, 3075 EA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
New Zealand
Wellington Cancer Centre
Wellington, New Zealand, 6039
Slovakia
National Cancer Institute - Bratislava
Bratislava, Slovakia, 833 10
Spain
Hospital de la Santa Cruz I Sant Pau
Barcelona, Spain, 08025
Hospital General de Asturias
Oviedo, Spain, 33006
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Instituto Valenciano De Oncologia
Valencia, Spain, 46009
Sweden
Lund University Hospital
Lund, Sweden, S-22185
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
United Kingdom, England
Christie Hospital N.H.S. Trust
Manchester, England, United Kingdom, M20 4BX
Middlesex Hospital- Meyerstein Institute
London, England, United Kingdom, WIT 3AA
Mount Vernon Hospital
Northwood, England, United Kingdom, HA6 2RN
Newcastle General Hospital
Newcastle Upon Tyne, England, United Kingdom, NE4 6BE
Nottingham City Hospital NHS Trust
Nottingham, England, United Kingdom, NG5 1PB
Royal Marsden NHS Trust
London, England, United Kingdom, SW3 6JJ
St. James's Hospital
Leeds, England, United Kingdom, LS9 7TF
Weston Park Hospital
Sheffield, England, United Kingdom, S1O 2SJ
United Kingdom, Scotland
Beatson Oncology Centre
Glasgow, Scotland, United Kingdom, G11 6NT
United Kingdom, Wales
Velindre Hospital
Cardiff, Wales, United Kingdom, CF4 7XL
Sponsors and Collaborators
Cancer and Leukemia Group B
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Investigators
Study Chair: George D. Demetri, MD Dana-Farber Cancer Institute
Study Chair: George D. Demetri, MD Dana-Farber Cancer Institute
Study Chair: Ronald H. Blum, MD Beth Israel Medical Center
Study Chair: Vivien H.C. Bramwell, MB, BS, PhD, FRCP London Regional Cancer Program at London Health Sciences Centre
  More Information

Additional Information:
Publications:
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32.
Heinrich MC, Owzar K, Corless CL, Hollis D, Borden EC, Fletcher CD, Ryan CW, von Mehren M, Blanke CD, Rankin C, Benjamin RS, Bramwell VH, Demetri GD, Bertagnolli MM, Fletcher JA. Correlation of Kinase Genotype and Clinical Outcome in the North American Intergroup Phase III Trial of Imatinib Mesylate for Treatment of Advanced Gastrointestinal Stromal Tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008 Oct 27; [Epub ahead of print]
Blackstein ME, Rankin C, Fletcher C, et al.: Clinical benefit of imatinib in patients (pts) with metastatic gastrointestinal stromal tumors (GIST) negative for the expression of CD117 in the S0033 trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-9010, 818s, 2005.
Dileo P, Rankin CJ, Benjamin RS, et al.: Incidence and reasons for dose modification of standard-dose vs. high-dose imatinib mesylate (IM) in the phase III Intergroup study S0033 of patients (pts) with unresectable or metastatic gastrointestinal stromal tumor (GIST). [Abstract] J Clin Oncol 23 (Suppl 16): A-9032, 824s, 2005.
Heinrich MC, Shoemaker JS, Corless CL, et al.: Correlation of target kinase genotype with clinical activity of imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT (KIT+). [Abstract] J Clin Oncol 23 (Suppl 16): A-7, 3s, 2005.
Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, Johnson MM, Macapinlac HA, Podoloff DA. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol. 2004 Dec;183(6):1619-28.
Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34.
Benjamin RS, Rankin C, Fletcher C, et al.: Phase III dose-randomized study of imatinib mesylate (STI571) for GIST: Intergroup S0033 early results. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3271, 2003.
Choi H, Charnsangavej C, Macapinlac HA, et al.: Correlation of computerized tomography (CT) and proton emission tomography (PET) in patients with metastatic GIST treated at a single institution with imatinib mesylate. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3290, 2003.
Demetri GD, Rankin C, Fletcher C, et al.: Phase III dose-randomized study of imatinib mesylate (Gleevec, STI571) for GIST: intergroup S0033 early results. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1651, 2002.
van Glabbeke MM, Owzar K, Rankin C, et al.: Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): a meta-analyis based on 1,640 patients (pts). [Abstract] J Clin Oncol 25 (Suppl 18): A-10004, 546s, 2007.

Study ID Numbers: CDR0000068422, CLB-80004, CAN-NCIC-S0033, E-S0033, SWOG-S0033, INT-S0033
Study First Received: February 2, 2001
Last Updated: February 13, 2009
ClinicalTrials.gov Identifier: NCT00009906     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
gastrointestinal stromal tumor

Additional relevant MeSH terms:
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Imatinib
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Gastrointestinal Neoplasms
Gastrointestinal Stromal Tumors

ClinicalTrials.gov processed this record on November 27, 2009