Imatinib Mesylate in Treating Patients With Recurrent Small Cell Lung Cancer

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.

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