Clinical trial NCT00368927: Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
Official title: Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Precancerous Condition
Stage I Non-small Cell Lung Cancer
Tobacco Use Disorder
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-08-29
Enrollment: 61
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
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
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Percent Change in Number of Dysplastic Lesions (DL) as Measured by Mucosal Biopsy Samples Before and After the Intervention
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Vancouver
country: Canada
facility: British Columbia
state: British Columbia
Study officials:
affiliation: Mayo Clinic
name: James Jett
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.