Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
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Purpose
This randomized phase II trial is studying sulindac to see how well it works compared to a placebo in preventing lung cancer in current or former smokers with bronchial dysplasia. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of sulindac may prevent lung cancer from forming in patients with bronchial dysplasia. It is not yet known whether sulindac is more effective than a placebo in preventing lung cancer in patients with bronchial dysplasia.
| Condition | Intervention | Phase |
|---|---|---|
|
Precancerous Condition Stage I Non-small Cell Lung Cancer Tobacco Use Disorder |
Drug: sulindac Other: placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention |
| Official Title: | Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia |
- Response determined by change in histologic grade of bronchial dysplasia as measured by mucosal biopsy samples before and after treatment [ Time Frame: Baseline and 30 days ] [ Designated as safety issue: No ]Will be explored graphically within and across the two intervention arms. The two-sample Smirnov test (a non-linear rank test based on hypergeometric distribution) will be used to perform a more thorough analysis of ordered categories. Odds ratios along with 95% confidence intervals will be estimated.
- Change in number of dysplastic lesions as measured by mucosal biopsy samples before and after treatment [ Time Frame: Pre-intervention and post-intervention ] [ Designated as safety issue: No ]Will be analyzed within and between the two intervention groups using paired t-tests and two-sample t-tests. Univariate and multivariate regression models will be fit using percent change in the number of bronchial dysplastic lesions as the response variable and intervention group, smoking status, demographic features and other clinical characteristics as predictor variables, as appropriate. Pending distribution of the data, change in the number of dysplastic lesions within each participant will be categorized and compared by intervention group using Fisher's exact test or the chi-square test.
| Enrollment: | 132 |
| Study Start Date: | August 2006 |
| Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive oral sulindac twice daily for 6 months.
|
Drug: sulindac
Given orally
Other Names:
|
|
Placebo Comparator: Arm II
Patients receive oral placebo twice daily for 6 months.
|
Other: placebo
Given orally
Other Name: PLCB
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Compare the change in histologic grade of bronchial dysplasia, as determined from mucosal biopsy samples obtained during pre- and post-intervention autofluorescence bronchoscopy exams, in current or former smokers with bronchial dysplasia treated with sulindac vs placebo.
SECONDARY OBJECTIVES:
I. Compare the change in number of dysplastic lesions, as determined from mucosal biopsy samples obtained during pre- and post-intervention autofluorescence bronchoscopy exams, in patients treated with these regimens.
II. Compare changes in tissue-based biomarkers (cyclooxygenase [COX]-2, 15-lipoxygenase [LOX]-1, PPAR γ, Ki-67, caspase-3, cyclin D1, cyclin E) in patients treated with these regimens.
III. Determine the safety and adverse event profiles of these regimens in these patients.
IV. Describe the frequency and patterns of bronchial dysplasia as well as biomarker characteristics in patients treated with this regimen.
V. Establish a biospecimen repository archive for future correlative studies.
OUTLINE: This is a multicenter, double-blind, randomized, placebo-controlled study. Patients are stratified according to smoking status (current vs former), prior lung cancer (yes vs no), and number of baseline dysplastic lesions (1-3 vs > 3). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral sulindac twice daily for 6 months.
ARM II: Patients receive oral placebo twice daily for 6 months. Bronchoscopic examination and mucosal biopsy are performed at baseline and at completion of study treatment. Tissue samples are examined by immunohistochemistry for biological markers, including Ki-67, caspase-3, cyclooxygenase-2, cyclin D1, cyclin E, vascular endothelial growth factor, PPAR γ, and 15-lipoxygenase-1. Blood samples are collected for serum cotinine.
After completion of study treatment, patients are followed for up to 30 days.
Eligibility| Ages Eligible for Study: | 40 Years to 79 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Current or former smoker who has smoked at least 30 pack years AND meets 1 of the following criteria:
- No prior lung cancer
- Prior stage I non-small cell lung cancer(NSCLC) that was completely resected ≥ 1 year ago OR for which patient completed adjuvant chemotherapy ≥ 1 year ago
- Tissue blocks, blood, and sputum samples available for research purposes
- No carcinoma in situ
- ECOG performance status 0-1
- Hemoglobin ≥ 12.0 g/dL (women) or hemoglobin ≥ 13.5 g/dL (men)
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥30 mL/min
- Room air oxygen saturation ≥ 90%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Negative chest x-ray
- Negative electrocardiogram
No other cancer within the past 3 years except nonmelanoma skin cancer, localized prostate, carcinoma in situ of the cervix cancer, or superficial bladder cancer
- Treatment must have been completed > 6 months ago
- No prior gastrointestinal ulceration, bleeding, or perforation
No uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Myocardial infarction within the past 6 months
- Chronic renal disease
- Chronic liver disease
- Difficult to control hypertension
- Psychiatric illness or social situations that would limit study compliance
- No known HIV positivity
- No history of allergic reactions or hypersensitivity to sulindac or other NSAIDs, including aspirin-sensitive asthma or urticaria
- No known sensitivity to yellow dye FD&C Yellow #5
- No continuous or intermittent supplemental oxygen
- At least 6 months since prior participation in another chemoprevention trial
- At least 6 months since prior regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids (may be eligible after washout period of 12 weeks for NSAIDs and 6 weeks for corticosteroids)
- No prior pneumonectomy
- No prior solid organ transplantation
- No other concurrent investigational agents
No concurrent regular use of acetylsalicylic acid (aspirin) unless prescribed by a physician for prevention
- Maximum of 1 aspirin (81 mg) per day allowed
No concurrent use of any of the following:
- Methotrexate
- Corticosteroids
Antiplatelet agents:
- Warfarin
- Ticlopidine
- Clopidogrel bisulfate
- Aspirin
- Abciximab
- Dipyridamole
- Eptifibatide
- Tirofiban hydrochloride
- Lithium carbonate
- Cyclosporine
- Hydralazine
- Angiotensin-converting enzyme (ACE) inhibitors (ACE receptor antagonists are allowed)
- Angiotensin receptor blockers
Contacts and Locations| United States, Florida | |
| H. Lee Moffitt Cancer Center and Research Institute | |
| Tampa, Florida, United States, 33612 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| Principal Investigator: | James Jett | Mayo Clinic |
More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00368927 History of Changes |
| Other Study ID Numbers: | NCI-2009-00836, MAYO-03-1-02, CDR0000496457, MAY03-1-02, N01CN35000 |
| Study First Received: | August 24, 2006 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Federal Government |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Precancerous Conditions Tobacco Use Disorder Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Substance-Related Disorders Mental Disorders Sulindac |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Cyclooxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 23, 2013