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