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: November 20, 2013
Last verified: November 2013

August 24, 2006
November 20, 2013
August 2006
May 2010   (final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00368927 on ClinicalTrials.gov Archive Site
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.
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Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Precancerous Condition
  • Stage I Non-small Cell Lung Cancer
  • Tobacco Use Disorder
  • Drug: sulindac
    Given orally
    Other Names:
    • Aflodac
    • Algocetil
    • Clinoril
    • SULIN
  • Other: placebo
    Given orally
    Other Name: PLCB
  • Experimental: Arm I
    Patients receive oral sulindac twice daily for 6 months.
    Intervention: Drug: sulindac
  • Placebo Comparator: Arm II
    Patients receive oral placebo twice daily for 6 months.
    Intervention: Other: placebo
Limburg PJ, Mandrekar SJ, Aubry MC, Ziegler KL, Zhang J, Yi JE, Henry M, Tazelaar HD, Lam S, McWilliams A, Midthun DE, Edell ES, Rickman OB, Mazzone P, Tockman M, Beamis JF, Lamb C, Simoff M, Loprinzi C, Szabo E, Jett J; Cancer Prevention Network. Randomized phase II trial of sulindac for lung cancer chemoprevention. Lung Cancer. 2013 Mar;79(3):254-61. doi: 10.1016/j.lungcan.2012.11.011. Epub 2012 Dec 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
132
Not Provided
May 2010   (final data collection date for primary outcome measure)

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
Both
40 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00368927
NCI-2009-00836, NCI-2009-00836, CDR0000496457, MAY03-1-02, MAYO-03-1-02, MAY03-1-02, N01CN35000
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: James Jett Mayo Clinic
National Cancer Institute (NCI)
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP