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

NCT02348203 | Completed Phase 2 Results DMC

• 6 other identifiers: NCI-2015-00061N01-CN-2012-000311403269898UAZ2013-02-01N01CN00031P30CA023074
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Tobacco Use Disorder

Outcome Measures

Primary Outcomes (1)

• Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers

  Change in a nasal smoking-related gene expression signature score derived from prior research was compared between the two study arms. Prior research showed that a higher score was observed in never smokers compared to current smokers. An increased score implicated a more favorable intervention effect. There is no minimum or maximum score.

  Baseline to 12 weeks (End-of-intervention)

Secondary Outcomes (10)

• Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers

  Baseline to 12 weeks (End of Intervention)

• Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention

  Baseline to 14 days post intervention

• Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention

  Baseline to 14 days post intervention

• Change in Urinary PGE-M Levels

  Baseline to 12 weeks (End-of-intervention)

• Change in Urinary LTE (4) Levels

  Baseline to 12 weeks (End-of-intervention)

Study Arms (2)

Arm I (aspirin, zileuton)

EXPERIMENTAL

Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.

Drug: Aspirin; Other: Laboratory Biomarker Analysis; Drug: Zileuton

Arm II (double placebo)

PLACEBO COMPARATOR

Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.

Other: Laboratory Biomarker Analysis; Other: Placebo Administration

Interventions

Aspirin DRUG

Given PO

Also known as: Acetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin

Arm I (aspirin, zileuton)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (aspirin, zileuton); Arm II (double placebo)

Placebo Administration OTHER

Given aspirin placebo PO

Arm II (double placebo)

Zileuton DRUG

Given PO

Also known as: Zyflo

Arm I (aspirin, zileuton)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current tobacco smokers with \>= 20 pack years of self-reported smoking exposure and an average use of \>= 10 cigarettes/day
• Karnofsky \>= 70%
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Hematocrit \>= the lower institutional limit
• Platelets \>= the lower institutional limits
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) within normal institutional limits
• Creatinine =\< the upper institutional limits
• Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional limits
• Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• History of allergic reaction to aspirin or attributed to compounds of similar chemical or biologic composition to aspirin, including other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Gastric intolerance attributable to ASA or NSAIDs
• History of gastric ulcer within the past 5 years (with or without bleeding)
• Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment
• Not willing or are unable to refrain from use of any non-study ASA, NSAIDs and leukotriene antagonists during the study period
• Adult asthma
• Chronic, current or recent (within the past three months) use of leukotriene antagonists
• Require chronic anticoagulation or anti-platelet therapy
• History of bleeding disorder or hemorrhagic stroke
• Chronic, current or recent (within the past three months) use of glucocorticoids (systemic, topical and/or nasal sprays or steroid topical creams to large body surface area); use of steroid topical creams for small body areas (=\< 10% body surface) during study intervention is allowed
• History of chronic sinusitis or recent nasal polyps
• History of, or current, active or chronic liver disease even if transaminases have normalized
• History of allergic reaction to zileuton or attributed to compounds of similar chemical or biologic composition to zileuton
• Are taking drugs known to interact with zileuton, including theophylline, warfarin, and propranolol
• Not willing or are unable to limit alcohol consumption to =\< 2 alcoholic beverages a day during the study period

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Aspirin; zileuton

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Sherry Chow
• Organization: University of Arizona

schow@azcc.arizona.edu

520-626-3358

Study Officials

• Linda L Garland

  The University of Arizona Medical Center-University Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: January 28, 2015
• Study Start: January 13, 2016
• Primary Completion: February 22, 2019
• Study Completion: March 9, 2021
• Last Updated: June 2, 2022
• Results First Posted: March 23, 2020

Record last verified: 2022-06

Locations

US (2)