Imatinib Mesylate in Treating Patients With Recurrent Small Cell Lung Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent small cell lung cancer. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the response rate, time to progression, and overall survival of patients with recurrent small cell lung cancer treated with imatinib mesylate. II. Correlate the presence of c-Kit mutations in tumor tissue with treatment response in patients treated with this drug. III. Correlate individual patient variation in clinical (toxicity and/or activity), pharmacologic (pharmacokinetic/pharmacodynamic parameters), and/or biologic (correlative laboratory study results) responses to this drug with genetic differences in proteins involved in drug response (transport, metabolism, and/or mechanism of action). OUTLINE: This is a multicenter study. Patients are stratified according to length of prior therapy (less than 3 months vs at least 3 months). Patients receive oral imatinib mesylate twice daily for 28 days. Courses continue in the absence of disease progression or unacceptable toxicity. *Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after registration. NOTE: *Patients who develop CNS metastasis as the only site of disease progression receive therapeutic whole-brain radiotherapy and then resume study therapy. PROJECTED ACCRUAL: A total of 41 patients for stratum I will be accrued within 21 months and 50 patients for stratum II will be accrued within 25 months for this study.

Official Title
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Phase II Trial of STI571 in Patients With Relapsed Small Cell Lung Cancer

Conditions
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Recurrent Small Cell Lung Cancer

Intervention / Treatment
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* Drug: imatinib mesylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer (SCLC) No mixed histology Must have received only 1 prior treatment regimen (e.g., cyclophosphamide, doxorubicin, and vincristine alternating with etoposide and cisplatin allowed) c-Kit positive by immunohistochemistry (at least 1+) At least 1 unidimensionally measurable lesion Longest diameter at least 20 mm No uncontrolled CNS metastasis Treated CNS metastasis allowed Performance status - ECOG 0-2 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Total bilirubin no greater than 1.5 times upper limit of normal (ULN) Direct bilirubin no greater than ULN Creatinine no greater than 1.5 times ULN No unstable angina pectoris No uncontrolled congestive heart failure within the past 3 months unless ejection fraction is greater than 40% No myocardial infarction within the past 3 months No uncontrolled infection No other malignancy within the past 3 years except skin cancer or localized prostate cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study participation See Disease Characteristics More than 3 weeks since prior chemotherapy More than 2 weeks since prior radiotherapy No concurrent radiotherapy(including palliative therapy for bone pain) Concurrent whole-brain radiotherapy for CNS progression allowed More than 3 weeks since prior major surgery No prior imatinib mesylate

Ages Eligible for Study
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Minimum Age: 18 Years

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: Treatment (imatinib mesylate)<br>Patients receive oral imatinib mesylate twice daily for 28 days. Courses continue in the absence of disease progression or unacceptable toxicity. | Drug: imatinib mesylate<br>* Given orally<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients progression-free | Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time | Estimated using the method of Kaplan-Meier. | From registration to death due to any cause, assessed up to 3 years | 
| Time to disease progression | Estimated using the method of Kaplan-Meier. | From randomization to documentation of disease progression, assessed up to 3 years | 
| Duration of response (complete response [CR] or partial response [PR]) |  | The date from which the patient's objective status if first noted to be either a CR or PR to the date progression is documented, assessed up to 3 years | 
| Time to treatment failure |  | From the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 3 years | 
| Toxicity defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, per the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0 | The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. | Up to 3 years |