Imatinib Mesylate and Paclitaxel in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well giving imatinib mesylate together with paclitaxel works in treating older patients with stage IIIB or stage IV non-small cell lung cancer. 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 paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with paclitaxel may kill more tumor cells

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the clinical efficacy of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer. SECONDARY OBJECTIVES: I. To evaluate the safety profile of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer. II. To collect paraffin tissue blocks for a companion project evaluating the expression of platelet derived growth factor (PDGF) by original tumor specimens, and its relationship to response rate and survival. OUTLINE: Patients receive paclitaxel intravenously (IV) on days 3, 10, and 17 and imatinib mesylate orally (PO) once daily (QD) on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

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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Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV 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: Histologic or cytologic diagnosis of non-small cell lung cancer At least one site of measurable disease, as defined by the modified RECIST criteria 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 Total bilirubin < 1.25 x upper limit of normal (ULN) Baseline absolute neutrophil count >= 1500/uL Baseline platelet count >= 100,000/uL ECOG Performance Status 0, 1 or 2 at the time of informed consent 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 AST and ALT =< 2.5 x ULN Creatinine =< 1.5 x ULN 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 The administration of any other anticancer agents including chemotherapy and biologic agents is NOT permitted The use of other concurrent investigational drugs is not allowed Participants in this study must avoid grapefruit juice or other grapefruit-containing products for the duration of treatment with imatinib

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: Treatment (enzyme inhibitor, chemotherapy)<br>Patients receive paclitaxel IV on days 3, 10, and 17 and imatinib mesylate PO QD on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. | Drug: imatinib mesylate<br>* Given PO<br>* Other names: Glivec;Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Baseline, Week 4 of courses 2, 4 and 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Baseline and every 2 months post treatment until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed up to 5 years. | 
| Overall Survival |  | Every 3 months for 5 years |