Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor

NCT00685828 | Unknown Phase 3

• 4 other identifiers: EORTC-62005AGITG-AGO102-GISTISG-62005SSG-15
• Study Type: interventional
• Target: 946
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which dose of imatinib mesylate is more effective in treating gastrointestinal stromal tumor. PURPOSE: This randomized phase III trial is studying two different doses of imatinib mesylate to compare how well they work in treating patients with unresectable or metastatic gastrointestinal stromal tumor.

Conditions

Gastrointestinal Stromal Tumor

Keywords

gastrointestinal stromal tumor

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

Secondary Outcomes (3)

• Overall survival

• Objective tumor response

• Toxicity as assessed by NCI CTC v2.0

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive low-dose oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity.

Drug: imatinib mesylate

Arm II

EXPERIMENTAL

Patients receive high-dose oral imatinib mesylate twice daily in the absence of disease progression or unacceptable toxicity.

Drug: imatinib mesylate

Interventions

imatinib mesylate DRUG

By mouth

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed gastrointestinal stromal tumor (GIST) * Metastatic or unresectable disease * Immunohistochemical confirmation of KIT (CD117) expression by tumor as documented by DAKO antibody staining * Measurable or non-measurable disease by conventional imaging (CT scan or MRI) or physical examination * If a target lesion has been previously embolized or irradiated, there must be objective evidence of progression to be considered for response assessment * No known brain metastasis PATIENT CHARACTERISTICS: * WHO performance status 0-3 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if hepatic metastases are present) * Creatinine ≤ 1.5 times ULN * ANC ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL (transfusions allowed) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study therapy * No NYHA class III-IV cardiac disease * No congestive heart failure or myocardial infarction within the past 2 months * No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection \[e.g., HIV\]) * No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * No medical, psychological, familial, sociological, or geographical condition that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete study treatment, comply with study protocol and follow-up schedule, or give reliable informed consent PRIOR CONCURRENT THERAPY: * Recovered from all prior therapy * More than 28 days since prior chemotherapy, biologic therapy, or any other investigational drug * More than 14 days since prior major surgery * No concurrent therapeutic anticoagulation with coumarin derivatives * Concurrent therapeutic anticoagulation with low-molecular weight heparin allowed * Concurrent mini-dose coumarin derivatives (i.e., equivalent to 1 mg of oral warfarin daily) as prophylaxis allowed * No concurrent cytokines (i.e., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\]) to support blood counts * No other concurrent investigational drugs * No other concurrent anticancer agents, including chemotherapy, radiotherapy, or anticancer biologic therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Italian Sarcoma Group: collaborator
• Australasian Gastro-Intestinal Trials Group: collaborator
• Scandinavian Sarcoma Group: collaborator

Related Publications (10)

• Judson I. Imatinib in advanced gastrointestinal stromal tumour: when is 800 mg the correct dose? Curr Opin Oncol. 2008 Jul;20(4):433-7. doi: 10.1097/CCO.0b013e328302ed96.

  PMID: 18525340 BACKGROUND

• 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.

  BACKGROUND

• Le Cesne A, Van Glabbeke M, Verweij J, Casali PG, Findlay M, Reichardt P, Issels R, Judson I, Schoffski P, Leyvraz S, Bui B, Hogendoorn PC, Sciot R, Blay JY. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol. 2009 Aug 20;27(24):3969-74. doi: 10.1200/JCO.2008.21.3330. Epub 2009 Jul 20.

  PMID: 19620483 RESULT

• Van Glabbeke MM, Verweij J, Casali P, et al.: Type of progression in patients treated with imatinib for advanced gastrointestinal stromal tumor (GIST): A study based on the EORTC-ISG-AGITG trial 62005. [Abstract] J Clin Oncol 27 (Suppl 15): A-10536, 2009.

  RESULT

• Sciot R, Debiec-Rychter M, Daugaard S, Fisher C, Collin F, van Glabbeke M, Verweij J, Blay JY, Hogendoorn PC; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Trials Group. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours (GISTs): An analysis of the EORTC phase III trial of treatment of metastatic GISTs with imatinib mesylate. Eur J Cancer. 2008 Sep;44(13):1855-60. doi: 10.1016/j.ejca.2008.06.003. Epub 2008 Jul 22.

  PMID: 18653326 RESULT

• Verweij J, Casali PG, Kotasek D, Le Cesne A, Reichard P, Judson IR, Issels R, van Oosterom AT, Van Glabbeke M, Blay JY. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer. 2007 Apr;43(6):974-8. doi: 10.1016/j.ejca.2007.01.018. Epub 2007 Mar 2.

  PMID: 17336514 RESULT

• Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006 May;42(8):1093-103. doi: 10.1016/j.ejca.2006.01.030. Epub 2006 Apr 18.

  PMID: 16624552 RESULT

• Van Glabbeke M, Verweij J, Casali PG, Simes J, Le Cesne A, Reichardt P, Issels R, Judson IR, van Oosterom AT, Blay JY. Predicting toxicities for patients with advanced gastrointestinal stromal tumours treated with imatinib: a study of the European Organisation for Research and Treatment of Cancer, the Italian Sarcoma Group, and the Australasian Gastro-Intestinal Trials Group (EORTC-ISG-AGITG). Eur J Cancer. 2006 Sep;42(14):2277-85. doi: 10.1016/j.ejca.2006.03.029. Epub 2006 Jul 28.

  PMID: 16876399 RESULT

• Van Glabbeke M, Verweij J, Casali PG, Le Cesne A, Hohenberger P, Ray-Coquard I, Schlemmer M, van Oosterom AT, Goldstein D, Sciot R, Hogendoorn PC, Brown M, Bertulli R, Judson IR. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol. 2005 Aug 20;23(24):5795-804. doi: 10.1200/JCO.2005.11.601.

  PMID: 16110036 RESULT

• Verweij J, Casali PG, Zalcberg J, et al.: Early efficacy comparison of two doses of imatinib for the treatment of advanced gastro-intestinal stromal tumors (GIST): interim results of a randomized phase III trial from the EORTC-STBSG, ISG and AGITG. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3272, 814, 2003.

  RESULT

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Jacob Verweij, MD, PhD

  Daniel Den Hoed Cancer Center at Erasmus Medical Center

  STUDY CHAIR

• Paolo G. Casali, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY CHAIR

• John R. Zalcberg, MB, BS, PhD, FRACP

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

• Kirsten Sundby Hall, MD

  Lund University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 28, 2008
• Study Start: January 1, 2001
• Primary Completion: February 1, 2002
• Last Updated: July 4, 2014

Record last verified: 2014-07