Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Prevention Active 40 to 79 NCI MAYO-03-1-02 MAY03-1-02, NCT00368927

Objectives

Primary

1. 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

1. 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.
2. 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.
3. Determine the safety and adverse event profiles of these regimens in these patients.
4. Describe the frequency and patterns of bronchial dysplasia as well as biomarker characteristics in patients treated with this regimen.
5. Establish a biospecimen repository archive for future correlative studies.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

• See Disease Characteristics
• 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
• No continuous or intermittent supplemental oxygen

Patient Characteristics:

• 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

Expected Enrollment

A total of 132 patients will be accrued for this study.

Outcomes

Change in histologic grade of bronchial dysplasia as measured by mucosal biopsy samples before and after treatment

Change in number of dysplastic lesions as measured by mucosal biopsy samples before and after treatment
Changes in tissue-based biomarkers (cyclooxygenase-2, 15-lipoxygenase-1, PPAR γ, Ki-67, caspase-3, cyclin D1, cyclin E, and vascular endothelial growth factor) by immunohistochemistry
Safety and adverse events
Frequency and patterns of bronchial dysplasia
Establishment of a biospecimen repository

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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

James Jett, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

U.S.A.
Florida
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute	Ph:  800-456-7121
			Email: canceranswers@moffitt.org
Massachusetts
	Burlington
	Lahey Clinic Medical Center - Burlington
		Clinical Trials Office - Lahey Clinic Medical Center - Burlington	Ph:  781-744-8027
Michigan
	Detroit
	Josephine Ford Cancer Center at Henry Ford Hospital
		Michael Simoff, MD	Ph:  313-916-4406 888-734-5322
			Email: msimoff1@hfhs.org
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Ohio
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100
Pennsylvania
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Clinical Trials Office - Fox Chase Cancer Center - Philadelphia	Ph:  215-728-4790
Canada
British Columbia
	Vancouver
	British Columbia Cancer Agency - Vancouver Cancer Centre
		Stephen Lam, MD	Ph:  604-877-6000 ext. 2080

Registry Information
Official Title		Randomized, Phase IIb Trial of Sulindac in Smokers with Bronchial Dysplasia
Trial Start Date		2006-08-04
Trial Completion Date		2010-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00368927
Date Submitted to PDQ		2006-07-13
Information Last Verified		2008-03-30
NCI Grant/Contract Number		CN35000