Imatinib Mesylate After Irinotecan and Cisplatin in Treating Patients With Extensive-Stage Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the 4-month progression-free survival rate in patients with c-kit positive, extensive stage small cell lung cancer treated with maintenance therapy comprising imatinib mesylate after induction therapy comprising irinotecan and cisplatin.

Secondary

• Determine the overall survival of patients treated with this regimen.
• Determine the tolerability of imatinib mesylate maintenance therapy in these patients.
• Determine the response rate in patients treated with irinotecan and cisplatin.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive irinotecan IV over 90 minutes on days 1 and 8 and cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response (partial or complete) or stable disease proceed to maintenance therapy.
• Maintenance therapy: Patients receive oral imatinib mesylate twice daily for 6 months in the absence of disease progression or unacceptable toxicity. Some patients may continue to receive therapy for up to 1 year.

After completion of study treatment, patients are followed for 4 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

• Extensive stage disease, defined by 1 of the following criteria:

• Disease extends beyond one hemithorax and regional lymph nodes
• Cytologically positive pleural effusion
• Meets 1 of the following criteria:

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion outside the field of any prior radiotherapy
• Evaluable disease
• No history of untreated or symptomatic brain or leptomeningeal metastases

• Prior brain metastases allowed provided patient is neurologically stable for 2 weeks after completion of therapy

PATIENT CHARACTERISTICS:

Performance status

• SWOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Meets 1 of the following criteria:

• Alkaline phosphatase (AP) normal AND AST and ALT ≤ 2.5 times ULN
• AP ≤ 5 times ULN AND AST and ALT normal
• No acute or chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 65 mL/min

Cardiovascular

• No uncontrolled congestive heart failure
• No uncontrolled angina
• No myocardial infarction and/or stroke within the past 3 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No peripheral neuropathy ≥ grade 2
• No symptomatic edema from any etiology
• No known HIV positivity
• No other serious medical illness
• No other malignancy within the past 3 years except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
• No history of dementia, active psychiatric disorder, or other condition that would preclude study compliance or ability to take oral medication on a daily basis

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy for SCLC

Endocrine therapy

• No concurrent routine systemic corticosteroids

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior palliative radiotherapy

Surgery

• More than 2 weeks since prior major surgery

Other

• No concurrent therapeutic anticoagulation with warfarin

• Concurrent low molecular weight heparin allowed provided regimen was initiated ≥ 2 weeks prior to study entry
• No other concurrent participation in another study of an investigational agent