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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00368927
First received: August 24, 2006
Last updated: May 7, 2014
Last verified: October 2011
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of Participants With Response Determined by Change in Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples Before and After Treatment [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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:
  • Percent Change in Number of Dysplastic Lesions (DL) as Measured by Mucosal Biopsy Samples Before and After the Intervention [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 61
Study Start Date: August 2006
Study Completion Date: December 2010
Primary Completion Date: May 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:
  • Aflodac
  • Algocetil
  • Clinoril
  • SULIN
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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368927

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Massachusetts
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States, 01805
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Canada, British Columbia
British Columbia
Vancouver, British Columbia, Canada, V5Z 1L3
Sponsors and Collaborators
Investigators
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, NCI-2009-00836, CDR0000496457, MAY03-1-02, MAYO-03-1-02, MAY03-1-02, P30CA015083, N01CN35000
Study First Received: August 24, 2006
Results First Received: November 14, 2013
Last Updated: May 7, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Tobacco Use Disorder
Precancerous Conditions
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Sulindac
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014