Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

Phase 2

Completed

Conditions: Tobacco Use Disorder
Precancerous Condition
Stage I Non-small Cell Lung Cancer

Interventions: Drug: sulindac
Other: placebo

Registration Number: NCT00368927

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	sulindac	Patients receive oral sulindac twice daily for 6 months.
Arm II	placebo	Patients receive oral placebo twice daily for 6 months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Response Determined by Change in Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples Before and After Treatment	Baseline and 6 months	Definition of response: complete response = regression of all dysplastic lesions (DL) to normal, hyperplasia or metaplasia with no new DL identified; partial response = regression of one or more, but not all of the DL with no new DL identified and no lesions worsening; progression = worsening at one or more sites by at least 2 histologic grades or appearance of any new DL that were not previously biopsied; stable disease = participants not classified as having a complete response, partial response, or progressive disease

Secondary Outcome Measures

Name	Time	Method
Percent Change in Number of Dysplastic Lesions (DL) as Measured by Mucosal Biopsy Samples Before and After the Intervention	Baseline and 6 months	The number of dysplastic lesions was recorded pre-intervention and post-intervention for each participant in each group. Change in the number of lesions was compared between the two intervention groups.

Trial Locations

Locations (6): British Columbia
🇨🇦
Vancouver, British Columbia, Canada
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸
Tampa, Florida, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Lahey Hospital and Medical Center
🇺🇸
Burlington, Massachusetts, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States