Study of Gleevec and Weekly Paclitaxel in Patients Aged 70 or Older With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will evaluate the clinical efficacy of combining Gleevec (imatinib mesylate), a PDGFR antagonist, with front-line, single-agent paclitaxel in a cohort of elderly patients with advanced, non-small cell lung cancer.

Detailed Description
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Paclitaxel 90 mg/m2 IV on days 3, 10, 17 Imatinib 600 mg/day, oral administration in 4-day pulses bracketing each paclitaxel infusion (days 1-4; 8-11; 15-18) Cycle length: 28 days Number of cycles: up to 6

Official Title
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A Phase II Study of Intermittent Gleevec® (Imatinib Mesylate) and Weekly Paclitaxel in Patients Aged 70 or Older With Advanced Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Imatinib mesylate
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 70 years Histologic or cytologic diagnosis of non-small cell lung cancer At least one site of measurable disease, as defined by the modified RECIST criteria (See section 7.6) Stage IIIB with pleural effusion or Stage IV disease. Includes patients who received surgery alone for early stage disease, now in relapse with advanced disease. Staging is according to the American Joint Committee on Cancer classification scheme, 6th edition.48 Adequate hepatic, renal and marrow function Liver function tests: total bilirubin < 1.25 x upper limit of normal (ULN), AST and ALT < 2.5 x ULN, Creatinine < 1.5 x ULN Baseline absolute neutrophil count > 1500/μL Baseline platelet count > 100,000/μL ECOG Performance Status 0, 1 or 2 at the time of informed consent. (See Appendix 1) Written, voluntary consent Patients with reproductive potential must use an acceptable contraceptive method. Such methods include: 1) Male hormonal contraception; 2) Partner without reproductive potential, including post-menopausal status or history of tubal ligation; 3) Partner with intrauterine device (IUD) or contraceptive vaginal ring; 4) Partner takes oral contraceptive pill, wears contraceptive patch, or has contraceptive implant; 5) Routine use of barrier method, such as condoms or diaphragm, during sexual intercourse. Exclusion Criteria: Uncontrolled brain metastasis. Patients with known brain metastasis must have completed treatment with surgery, radiation or both. In addition, they must be off corticosteroids. Symptomatic neuropathy (Grade 2 or higher) Prior chemotherapy for advanced non-small cell lung cancer. (Prior adjuvant, neoadjuvant, or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence.) Patient is < 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention Prior radiation therapy to > 25% of bone marrow Grade III/IV congestive heart failure, as defined by NYHA criteria, or myocardial infarction within 6 months. Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study. Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis. Major surgery two weeks prior to study treatment Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent Any condition requiring continuous administration of systemic corticosteroids. The patient is on therapeutic anti-coagulation with warfarin.

Ages Eligible for Study
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Minimum Age: 70 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: Imatinib mesylate + Paclitaxel<br>Paclitaxel 90 mg/m2 IV on days 3, 10, 17 Imatinib (Gleevec) 600 mg/day, oral administration in 4-day pulses bracketing each paclitaxel infusion (days 1-4; 8-11; 15-18) Cycle length: 28 days Number of cycles: up to 6 | Drug: Imatinib mesylate<br>* Imatinib (Gleevec) 600 mg/day, oral administration in 4-day pulses(days 1-4; 8-11; 15-18) Cycle length: 28 days Number of cycles: up to 6<br>* Other names: Gleevec;Drug: Paclitaxel<br>* Paclitaxel 90 mg/m2 IV on days 3, 10, 17 Cycle length: 28 days Number of cycles: up to 6<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response rates according to RECIST criteria (version 1.0) expressed as percentage of evaluable patients. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival as measured by the Kaplan-Meier method | 12 Months | 
| Progression Free Survival | Number of months post treatment without measurable progression according to RECIST criteria (version 1.0) | 12 months | 
| Toxicities | Adverse events of grade 3 or higher, according to CTCAE version 3 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Lung cancer,, Non-small cell lung cancer, Metastatic, Gleevec, elderly