Celecoxib in Preventing Lung Cancer in Former Heavy Smokers

OBJECTIVES:

• Determine the feasibility of chemoprevention of lung cancer with celecoxib in former heavy smokers at risk for developing primary or second primary lung cancer.
• Determine the safety and side effects of this drug in these patients.
• Determine the quality of life of patients treated with this drug.
• Determine the role of COX-2-specific inhibitors (e.g., celecoxib) on antitumor immunity within the lung microenvironment of these patients.
• Determine the effects of COX-2 inhibition on angiogenesis in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to presence of preinvasive lesions (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral placebo twice daily for 6 months.
• Arm II: Patients receive oral celecoxib twice daily for 6 months. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed every 6 months during treatment and then annually for up to 4 years.

Patients are followed annually for up to 4 years.

PROJECTED ACCRUAL: A total of 180 patients (90 per treatment arm) will be accrued for this study.

Inclusion criteria

• Heavy former smokers without prior history of NSCLC

• Age > 45
• Smoked for minimum of 30 pack years
• Former smokers with prior curative resection of surgical stage I NSCLC will be recruited and must be:

• Age > 18
• Smoked > 10 pack years
• Must have had pathological staging and the extent of disease documented. At least one nodal station each must have been biopsied and all biopsies must have been negative
• At least 6 months post curative resection of Stage I prior NSCLC, without evidence for recurrence or second primary lung cancer
• Normal blood chemistry and cell counts
• Negative pregnancy test

Exclusion criteria

• Framingham 10-year-risk for coronary artery disease score > 10%
• History of cardiovascular disease
• Evidence of diffuse coronary calcification on screening CT
• Concurrent use of NSAIDs. The use of cardiac (baby) Aspirin is permitted
• Hypersensitivity to celecoxib, sulfonamides, aspirin or other NSAIDs
• Liver dysfunction [abnormally elevated liver function tests [transaminases (ALT, AST) > ULN, alkaline phosphatase (ALKP) > 1.5 ULN]] or history of cirrhosis
• No peptic ulcer disease (PUD) diagnosis nor active symptoms in the last 2 years or, if PUD was diagnosed < 2 years, there must be no active symptoms, and endoscopic confirmation of healing
• Renal dysfunction [abnormally elevated blood urea nitrogen (BUN) > 1.5 ULN and creatinine > ULN]
• End state respiratory disease
• Unstable angina or a history of significant coronary artery disease
• Other malignancies excluding non-melanoma type skin cancer and in situ cervical cancer. Persons with stage I/II head and neck cancer must be disease free for at least 12 months
• Pregnancy
• Lactation
• Unwillingness to practice contraception
• On systemic corticoid steroid therapy
• Coagulopathy
• Use of Coumadin
• Concurrent use of medication know to alter or be affected by alteration of hepatic p450 2C9 enzymes.
• Patients with concurrent medical conditions that may interfere with completion of tests, therapy, or the follow up schedule
• Patients who had received photosensitizing agents such as hematoporphyrin derivative or chemopreventive drugs such as retinoids within 3 months prior to the bronchoscopic procedure, radiotherapy to the chest, or cytotoxic chemotherapy agents
• Subject found to have CIS during screening bronchoscopy will be treated with local therapy prior to randomization