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

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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A Phase I Study Of STI 571 (Gleevec) In Combination With Cisplatin/Irinotecan In Patients With Extensive Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: imatinib mesylate
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: Age Not specified Performance status ECOG 0-1 OR Karnofsky 70-100% Life expectancy More than 6 weeks Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST and/or ALT ≤ 2.5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Gastrointestinal No concurrent untreated upper gastrointestinal bleeding that has not been fully investigated No gastrointestinal disease that would impair drug absorption Other 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 PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy No prior radiotherapy to more than 25% of marrow Surgery More than 3 weeks since prior major surgery No prior surgical procedure impairing absorption Other 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
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STI-571 with cisplatin and irinotecan<br> | Drug: cisplatin<br> <br> Drug: imatinib mesylate<br> <br> Drug: irinotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer, recurrent small cell lung cancer