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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving imatinib mesylate after irinotecan and cisplatin may keep the tumor from coming back. PURPOSE: This phase II trial is studying how well giving imatinib mesylate after irinotecan and cisplatin works in treating patients with extensive-stage small cell lung cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
Phase II Trial of Imatinib Mesylate Maintenance Therapy in Patients With C-Kit (+) Extensive-Stage Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: Cisplatin
* Drug: Gleevec™
* Drug: irinotecan


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan, Cisplatin & Gleevec™<br>Cisplatin 60mg/m2 IV day 1 every 21 days x 4 cycles Gleevec™ 400 mg po BID (800mg/day)- for patients with objective response or stable disease. Irinotecan 65 mg/m2 IV days 1, 8 every 21 days x 4 cycles | Drug: Cisplatin<br>* Cisplatin 60mg/m2 IV day 1 every 21 days x 4 cycles<br>* Other names: CDDP;Drug: Gleevec™<br>* Gleevac 400 mg po BID (800mg/day)- fo patients with objective response or stable disease.<br>* Other names: imatinib mesylate;Drug: irinotecan<br>* Irinotecan: 65 mg/m2 IV days 1, 8 every 21 days x 4 cycles<br>* Other names: CPT-11;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | at 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | at least 4 months after discontinuation of treatment | 
| Tolerability of Gleevec maintenance therapy |  | 30 days after completion of study treatment | 
| Response rate as measured by RECIST at |  | Baseline and every 8 weeks during study treatment | 

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