Celecoxib in Preventing Lung Cancer in Former Heavy Smokers

University of California, Los Angeles (UCLA)

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Other: placebo

Drug: celecoxib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00055978

U01CA096134 (U.S. NIH Grant/Contract)

UCLA-0108074

CDR0000271912

P30CA016042 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Chemoprevention therapy uses certain drugs to try to prevent the development or recurrence of cancer. Celecoxib may be effective in preventing the development or recurrence of lung cancer in former heavy smokers.

PURPOSE: Randomized phase II trial to study the effectiveness of celecoxib in preventing the development or recurrence of lung cancer in former heavy smokers who are at risk of developing cancer.

Full description

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.

Enrollment

112 patients

Sex

All

Ages

45+ years old

Volunteers

No Healthy Volunteers

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