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

Tobacco Use Disorder Clinical Trial

Official title:

Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00368927
• Other study ID #: NCI-2009-00836
• Secondary ID: NCI-2009-00836CD
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2006
• Last updated: May 7, 2014
• Start date: August 2006
• Est. completion date: December 2010

Study information

• Verified date: October 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: December 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 79 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Precancerous Condition
• Precancerous Conditions
• Stage I Non-small Cell Lung Cancer
• Tobacco Use Disorder

Intervention

Drug:
• sulindac
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
Canada	British Columbia	Vancouver	British Columbia
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Response Determined by Change in Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples Before and After Treatment	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	Baseline and 6 months	No
Secondary	Percent Change in Number of Dysplastic Lesions (DL) as Measured by Mucosal Biopsy Samples Before and After the Intervention	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.	Baseline and 6 months	No