Combination Chemotherapy and Imatinib Mesylate in Treating Patients With Extensive-Stage Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00052494
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 23, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto

January 24, 2003
January 27, 2003
July 23, 2015
April 2003
February 2009   (Final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00052494 on Archive Site
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Combination Chemotherapy and Imatinib Mesylate in Treating Patients With Extensive-Stage Small Cell Lung Cancer
A Phase I Study Of STI 571 (Gleevec) In Combination With Cisplatin/Irinotecan In Patients With Extensive Stage Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining cisplatin, irinotecan, and imatinib mesylate in treating patients who have extensive-stage small cell lung cancer.


  • Determine the maximum tolerated dose of imatinib mesylate when administered with cisplatin and irinotecan in patients with extensive stage small cell lung cancer.
  • Determine the recommended phase II dose of imatinib mesylate in patients treated with this regimen.
  • Determine the response rate, median duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of imatinib mesylate.

Patients receive cisplatin IV over 1 hour on day 1 and irinotecan IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for a maximum of 4 courses. Patients also receive oral imatinib mesylate daily continually for one week prior to, during, and after chemotherapy in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose (one dose level below the MTD).

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 1-2 years.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lung Cancer
  • Drug: cisplatin
  • Drug: imatinib mesylate
  • Drug: irinotecan hydrochloride
Experimental: STI-571 with cisplatin and irinotecan
  • Drug: cisplatin
  • Drug: imatinib mesylate
  • Drug: irinotecan hydrochloride
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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February 2009   (Final data collection date for primary outcome measure)


  • Histologically confirmed extensive stage small cell lung cancer

    • Incurable but amenable to treatment with chemotherapy
    • c-kit positive by immunohistochemistry of original biopsy or other metastatic site
  • At least one unidimensionally measurable lesion

    • > 20 mm by conventional techniques or > 10 mm by spiral CT scan
    • No prior radiotherapy to target measurable lesion(s), unless there is documented disease progression
  • No known brain metastases



  • Not specified

Performance status

  • ECOG 0-1 OR
  • Karnofsky 70-100%

Life expectancy

  • More than 6 weeks


  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • Bilirubin normal
  • AST and/or ALT ≤ 2.5 times upper limit of normal


  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min


  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • No concurrent untreated upper gastrointestinal bleeding that has not been fully investigated
  • No gastrointestinal disease that would impair drug absorption


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception prior to, during, and for 3 months after study participation
  • No history of ototoxicity
  • No history of peripheral neuropathy
  • No traumatic injury within the past 21 days
  • No ongoing or active infection
  • No other concurrent significant medical condition that would preclude study participation
  • No concurrent psychiatric condition or social situation that would preclude study compliance
  • No other malignancy within the past 5 years except treated nonmelanoma skin cancer, carcinoma in situ, or stage A prostate cancer


Biologic therapy

  • Not specified


  • See Disease Characteristics
  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy to more than 25% of marrow


  • More than 3 weeks since prior major surgery
  • No prior surgical procedure impairing absorption


  • No prior c-kit-targeted therapy
  • No concurrent therapeutic dose of warfarin

    • Mini-dose warfarin for prophylaxis and low-molecular weight heparin allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent amifostine
  • No other concurrent anticancer therapy
Sexes Eligible for Study: All
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
CDR0000258487 ( Registry Identifier: PDQ (Physician Data Query) )
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University Health Network, Toronto
University Health Network, Toronto
National Cancer Institute (NCI)
Study Chair: Mark D. Vincent, MD London Health Sciences Centre
University Health Network, Toronto
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP