Intermittent or Continuous Acetylsalicylic Acid and Gene Expression in the Nasal Tissue of Current Smokers

NCT ID: NCT02123849

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2018-02-28

Brief Summary

This randomized phase II trial studies the safety and effects of acetylsalicylic acid (aspirin) taken continuously or intermittently on gene expression in the nasal tissue of current smokers. Smokers are at increased risk of developing lung cancer. Acetylsalicylic acid may be useful in preventing lung cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To analyze the impact of a 12-week intervention of intermittent and continuous acetylsalicylic acid (ASA) on a smoking-related gene expression signature in the nasal epithelium of current smokers and to analyze any difference between the intermittent and continuous ASA interventions.

SECONDARY OBJECTIVES:

I. To determine whether the change in the smoking-related gene expression signature of nasal epithelium persists one week off agent intervention.

II. To compare the change in urinary prostaglandin E metabolite (PGE-M) and leukotriene E (4) (LTE [4]) between the continuous and intermittent dosing arms and to determine whether the change persists one week off agent intervention.

III. To analyze the impact of intermittent and continuous ASA on a three lung cancer-related gene signatures (an 80-gene signature, a phosphoinositide 3-kinase [PI3K] gene signature, and a nasal epithelium cancer signature) in the nasal epithelium and to analyze any difference between the intermittent and continuous ASA interventions.

IV. To determine whether the change, if any, in the lung cancer-related gene expression signatures of nasal epithelium persists one week off agent intervention.

V. To compare the safety in current smokers of 12 week exposure to continuous versus intermittent ASA.

VI. To evaluate a gender effect in the modulatory effects of intermittent and continuous ASA on smoking-related gene expression signature.

VII. To explore in a discovery-driven fashion the effect of ASA intervention on whole-genome gene expression.

VIII. To analyze the impact of intermittent and continuous ASA on karyometric analysis of buccal cells and to analyze any difference between intermittent and continuous ASA interventions.

OUTLINE: Participants are randomized to 1 of 2 treatment arms.

ARM I (CONTINUOUS): Participants receive aspirin orally (PO) once daily (QD) for 12 weeks.

ARM II (INTERMITTENT): Participants receive placebo PO QD during weeks 1, 3, 5, 7, 9, and 11 and aspirin PO QD during weeks 2, 4, 6, 8, 10, and 12.

After completion of study treatment, participants are followed up for 2 weeks.

Conditions

Lung Carcinoma; Tobacco Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm I (continuous aspirin)

Participants receive aspirin PO QD for 12 weeks.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Arm II (intermittent aspirin)

Participants receive placebo PO QD during weeks 1, 3, 5, 7, 9, and 11 and aspirin PO QD during weeks 2, 4, 6, 8, 10, and 12.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Placebo

Intervention Type: OTHER

Given PO

Interventions

Aspirin

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Placebo

Given PO

Intervention Type: OTHER

Other Intervention Names

Acetylsalicylic Acid; ASA; Aspergum; Ecotrin; Empirin; Entericin; Extren; Measurin; placebo therapy; PLCB; sham therapy

Eligibility Criteria

Inclusion Criteria

• Male or female 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 within normal institutional limits
• Platelets within normal institutional limits
• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 × institutional ULN
• 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
• 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

Exclusion Criteria

• 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 or NSAIDs 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)
• History of chronic sinusitis or recent nasal polyps
• Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
• Pregnant or lactating women; breastfeeding should be discontinued if the mother is treated with aspirin; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Have a known history of inability to absorb an oral agent
• Invasive cancer within the past five years except non-melanoma skin cancer
• Urine cotinine level, if collected at screening, does not confirm active smoking status

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda Garland

Role: PRINCIPAL_INVESTIGATOR

The University of Arizona Medical Center-University Campus

Locations

The University of Arizona Medical Center-University Campus

Tucson, Arizona, United States

Boston University School of Medicine

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

NCI-2014-01006

Identifier Type: REGISTRY

Identifier Source: secondary_id

N01-CN-2012-00031

Identifier Type: -

Identifier Source: secondary_id

HHSN2612012000311

Identifier Type: -

Identifier Source: secondary_id

1300000502

Identifier Type: OTHER

Identifier Source: secondary_id

UAZ2013-01-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN00031

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2014-01006

Identifier Type: -

Identifier Source: org_study_id