Celecoxib and Docetaxel in Treating Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may slow the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy and celecoxib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of celecoxib and docetaxel in treating patients who have non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the efficacy and feasibility of celecoxib combined with docetaxel as first-line therapy in elderly or poor performance status patients with advanced non-small cell lung cancer. Determine the response rate of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral celecoxib twice daily (beginning on day -7 of the first course) and docetaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses after CR. Patients who achieve stable disease (SD) or a partial response (PR) receive a minimum of 2 additional courses after SD or PR. At the discretion of the treating physician, patients then receive maintenance therapy comprising celecoxib only. Patients who discontinue therapy for disease progression or unacceptable toxicity are followed for at least 6 months. PROJECTED ACCRUAL: A total of 21-39 patients will be accrued for this study within 13-28 months.

Official Title
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Evaluation Of Celecoxib In Combination With Weekly Docetaxel In Elderly (70 Years) Or Poor Performance Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Celecoxib
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of non-small cell lung cancer (NSCLC) Stage IIIB with pleural effusion or stage IV disease Age 70 years and over with SWOG performance status 0-2 OR age 18 to 69 with SWOG performance status 2 Measurable or evaluable disease No symptomatic or untreated brain or leptomeningeal metastases Previously treated patients must be neurologically stable for 4 weeks after completion of appropriate therapy PATIENT CHARACTERISTICS: Age: See Disease Characteristics 18 and over Performance status: See Disease Characteristics SWOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL Hepatic: Bilirubin no greater than upper limit of normal (ULN) AST/ALT no greater than ULN (or no greater than 2.5 times ULN if alkaline phosphatase no greater than ULN) Alkaline phosphatase no greater than ULN (or no greater than 5 times ULN if AST/ALT no greater than ULN) No history of chronic hepatitis Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No uncontrolled congestive heart failure No uncontrolled angina No myocardial infarction and/or stroke within the past 6 months No active thromboembolic event within the past 4 weeks Gastrointestinal: No gastrointestinal bleeding within the past 6 months No history of peptic ulcer disease Other: No prior hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 No prior allergy to any non-steroidal anti-inflammatory drug No other prior or concurrent malignancy within the past 3 years except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix No grade 2 or greater peripheral neuropathy No other serious concurrent medical illness No history of dementia, active psychiatric disorder, or other condition that would interfere with ability to take oral medication or preclude compliance with study HIV negative Must weigh at least 50 kg (110 pounds) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for NSCLC Chemotherapy: No prior chemotherapy for NSCLC Endocrine therapy: At least 3 days since prior steroids Radiotherapy: At least 4 weeks since prior radiotherapy No prior radiotherapy to target lesion Surgery: At least 4 weeks since prior major surgery Other: Prior intermittent use of non-steroidal anti-inflammatory drugs (NSAIDs), including rofecoxib or celecoxib, allowed At least 1 week since prior fluconazole No recent prior NSAIDs, including rofecoxib or celecoxib, for a duration of more than 30 consecutive days No concurrent fluconazole or lithium No concurrent NSAIDs except aspirin administered at a dose of no more than 325 mg/day for cardiovascular conditions No other concurrent cyclo-oxygenase-2 inhibitors No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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: Celecoxib & Docetaxel<br>Celecoxib: On day -7 of the first cycle, patients will start, Celecoxib 400 mg po bid daily, each dose to give with meals Docetaxel: On day 1, 8, and 15 of each cycle patients will receive: Docetaxel 36mg/m2 over 60 minutes, duration of each cycle will be 28 days. | Drug: Celecoxib<br>* On day -7 of the first cycle, patients will start, Celecoxib 400 mg po bid daily, each dose to give with meals<br>* Other names: Celebra;Drug: Docetaxel<br>* On day 1, 8, and 15 of each cycle patients will receive: Docetaxel 36mg/m2 over 60 minutes, duration of each cycle will be 28 days.<br>* Other names: Taxotere®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of combining celecoxib with docetaxel in elderly (> or = 70 yrs old) or poor performance status (PS)of 2 | Blood levels of VEGF & PGE2 | Weeks 1, 2, and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of Celecoxib and Docetaxel | CT Chest/Abdomen | Every 2 cycles (or every 42 days); After therapy is completed or if the patient is only on Celecosxib, will be assessed for progression every month by clinical exam and every 3 months by radiological evaluation. | 
| Toxicity of Celecoxib and Docetaxel | Routine bloodwork | Weeks 1, 2, and 3 of each 28 day cycle | 
| Expression of cyclooxygenase-2 (COX-2) in tumors | Tissue sample from initial diagnosis, parrafin embedded tissue block | Pre-Study | 
| Changes in plasma levels of prostaglandin E2(PGE2) & vascular endothelial growth factor (VEGF) | Collecting blood plasma | Pre-study, Weeks 1, 2 and 5 | 

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