Gemcitabine and Imatinib Mesylate in Treating Patients With Recurrent or Metastatic Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with imatinib mesylate works in treating patients with recurrent or metastatic non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Evaluate the response rate in patients with recurrent or metastatic non-small cell lung cancer treated with gemcitabine hydrochloride and imatinib mesylate. Secondary Assess time to progression in patients treated with this regimen. Assess overall survival and 1-year survival of patients treated with this regimen. Assess the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, nonrandomized, uncontrolled, open-label study. Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Official Title
-----------------
Phase II Study of Imatinib Mesylate and Gemcitabine for Recurrent/Metastatic Non-small Cell Lung Cancer (NSCLC)

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

Intervention / Treatment
-----------------
* Drug: gemcitabine hydrochloride
* Drug: imatinib mesylate


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed non-small cell cancer Recurrent disease after adjuvant treatment OR progressive disease after 1 prior treatment for recurrent or metastatic disease Received at least 1 prior chemotherapy regimen and meets the following criteria: No more than 1 prior chemotherapeutic regimen in the recurrent or metastatic setting Patients who received prior chemotherapy in the adjuvant setting are eligible when 1 of the following criteria is met: In first recurrence (after 1 prior regimen) Received first-line chemotherapy in the recurrent setting after 2 prior regimens Measurable disease Must have ≥ 1 measurable target lesion outside prior radiotherapy field OR radiologic confirmation of disease progression within a prior radiotherapy field No known or untreated brain metastases or carcinomatous meningitis Clinically stable, treated brain metastases allowed provided it has been > 7 days since prior steroids PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment Able to swallow oral medication No concurrent medical condition that would preclude study compliance No history of allergic reaction to compounds of similar chemical or biological composition to gemcitabine hydrochloride or imatinib mesylate No uncontrolled illness that would preclude study compliance, including any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia requiring therapy Myocardial infarction within the past 6 months Active infection No New York Heart Association class III-IV congestive heart failure No chronic liver disease (i.e., chronic active hepatitis, cirrhosis) No HIV positivity No other primary malignancies within the past 5 years, except carcinoma in situ of the cervix or nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy and recovered At least 3 weeks since prior radiotherapy and recovered More than 28 days since prior and no other concurrent investigational or commercial agents More than 2 weeks since prior major surgery No prior gemcitabine hydrochloride or imatinib mesylate for metastatic disease No prior tyrosine kinase inhibitor, except for gefitinib or erlotinib hydrochloride No concurrent therapeutic warfarin (prophylactic warfarin therapy ≤ 1 mg daily allowed) No other concurrent medications that would preclude study compliance No concurrent chronic systemic corticosteroids

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: Gemcitabine hydrochloride and imatinib mesylate<br> | Drug: gemcitabine hydrochloride<br>* 1000 mg/m2 given intravenously at a FDR of 10 mg/m2/min on Days 3 and 10, every 21 days.<br>Drug: imatinib mesylate<br>* 400 mg/day orally, given Days 1-5 and 8-12 every 21 days<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Meet Critieria for Response | Response is considered Partial Response or Complete Response as per RECIST criteria. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression |  | 2 years | 
| 1-year Survival | Accrual duration is 2 years with an additional year for assessment of 1-year survival. Outcome measure time frame is about 3 years. | 3 years | 

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