NCT02348203

Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers

Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers.

Detailed description

PRIMARY OBJECTIVES: I. To analyze the impact of combined treatment of acetylsalicylic acid (ASA) (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control. SECONDARY OBJECTIVES: I. To assess the impact of ASA and zileuton on three lung cancer gene signatures (an 80-gene bronchial signature, a phosphatidylinositol 3-kinase \[PI3K\] pathway gene signature and a nasal diagnostic gene signature) and to compare this to placebo control. II. To determine whether the change in the smoking-related gene expression signature and the three lung cancer gene signatures of nasal epithelium persists 10-14 days off agent intervention. III. To measure urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE\[4\]) levels in current smokers after ASA and zileuton. IV. To assess the safety in current smokers of 12 week exposure to ASA and zileuton. V. To evaluate a gender effect in the modulatory effects of ASA and zileuton on smoking related-gene expression signature. VI. To explore the effect of ASA and zileuton on the metabolomics profile of the arachidonic acid pathway. VII. To explore, in a discovery-driven fashion, the effect of ASA and zileuton on whole-genome gene expression. VIII. To analyze the impact of ASA and zileuton on karyometric analysis of buccal cells. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive aspirin orally (PO) once daily (QD) and zileuton PO twice daily (BID) for 12 weeks in the absence of unacceptable toxicity. ARM II: Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks. After completion of study treatment, patients are followed up for 2 weeks.

Conditions

• Tobacco Use Disorder

Interventions

Type	Name	Description
DRUG	Aspirin	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Placebo Administration	Given aspirin placebo PO
OTHER	Placebo Administration	Given zileuton placebo PO
DRUG	Zileuton	Given PO

Timeline

• Start date: 2016-01-13
• Primary completion: 2019-02-22
• Completion: 2021-03-09
• First posted: 2015-01-28
• Last updated: 2022-06-02
• Results posted: 2020-03-23

Locations

2 sites across 1 country: United States