Lung CarcinomaPhase 2NCT02123849
Intermittent or Continuous Acetylsalicylic Acid and Gene Expression in the Nasal Tissue of Current Smokers
A Phase 2 study testing Aspirin and Laboratory Biomarker Analysis in people with Lung Carcinoma and Tobacco Use Disorder, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lung Carcinoma, Tobacco Use Disorder
- What is being tested?
- Aspirin and Laboratory Biomarker Analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2014to Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston University School of Medicine
Boston, Massachusetts, 02118
The University of Arizona Medical Center-University Campus
Tucson, Arizona, 85724
About this study
Official title: The Effect of Intermittent Versus Continuous Dose Aspirin (ASA) on Nasal Epithelium Gene Expression in Current Smokers
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- Aspirin, Laboratory Biomarker Analysis, Placebo
- Medical subject headings
- Lung Neoplasms, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called Acetylsalicylic Acid, ASA, Aspergum, Ecotrin
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (continuous aspirin) | Experimental | Participants receive aspirin PO QD for 12 weeks. Receives: Drug: Aspirin; Other: Laboratory Biomarker Analysis |
| Arm II (intermittent aspirin) | Experimental | 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. Receives: Drug: Aspirin; Other: Laboratory Biomarker Analysis; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
Change in 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.
Measured: Baseline to 12 weeks (End-of-Intervention)
Secondary outcomes (9)
Changes in Urine Leukotriene E4 (LTE(4)) Levels
Urinary LTE(4) was used as a biomarker 5-lipoxygenase (5-LOX) mediated arachidonic acid metabolism. Decreased LTE4 implicated inhibition of the 5-LOX mediated pathway.
Measured: Baseline to 12 weeks (End-of-Intervention)
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
Urinary PGE-M was used as a biomarker of cyclooxygenase (COX) mediated arachidonic acid metabolism. Decreased PGE-M implicated inhibition of COX mediated pathway.
Measured: Baseline to 12 weeks (End-of-Intervention)
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Measured: Up to 2 weeks post-treatment
Gender Effect on Smoking-related Gene Expression Signature Score
Change in nasal smoking-related gene expression signature score was compared between male and female participants. The gender comparison was not stratified by arm because of the small sample size. 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.
Measured: Baseline to 12 weeks (End-of-Intervention)
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
Change in lung cancer-related gene expression signature score derived from prior research was compared between the two study arms. Prior research showed that the score was higher in lung cancer cases than healthy controls. A decreased score implicated a more favorable intervention effect. There is no minimum or maximum score.
Measured: Baseline to 12 weeks (End-of-Intervention)
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Change in the lung cancer-related gene expression signature score from baseline to one week off agent intervention was compared between the two study arms. Prior research showed that higher scores were observed in lung cancer cases than healthy controls. A decreased score implicated a favorable intervention effect. There is no minimum or maximum score.
Measured: Baseline to 1 week post-intervention
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Change in nasal smoking-related gene expression signature score from baseline to 1 week post-intervention 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.
Measured: Baseline to 1 week post-intervention
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
Gene set enrichment analysis was performed on the MSigDB canonical pathways with the intent to discover differentially expressed genes after aspirin intervention.
Measured: Baseline to 12 weeks
Change in Buccal Cells Via Karyometric Analysis
Measured: Baseline to up to one week post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2014 (estimated)
- Study startJun 2014
- Primary completionSep 2016
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Linda Garland, Principal investigator, The University of Arizona Medical Center-University Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02123849
- Sponsor's protocol ID
- NCI-2014-01006
- Other IDs
- NCI-2014-01006, N01-CN-2012-00031, HHSN2612012000311, 1300000502, UAZ2013-01-01, N01CN00031, P30CA023074
- Status last verified
- Jul 2018
- First submitted
- 24 Apr 2014
- Last updated
- 29 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Intermittent Versus Continuous Dose Aspirin (ASA) on Nasal Epithelium Gene Expression in Current Smokers
- ClinicalTrials.gov ID
- NCT02123849
- Acronym / sponsor ID
- NCI-2014-01006
- Conditions
- Lung Carcinoma, Tobacco Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 28 Apr 2014 (estimated)
- Results
- Posted 29 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (continuous aspirin) | Experimental | Drug: Aspirin, Other: Laboratory Biomarker AnalysisParticipants receive aspirin PO QD for 12 weeks. |
| Arm II (intermittent aspirin) | Experimental | Drug: Aspirin, Other: Laboratory Biomarker Analysis, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAlso: Acetylsalicylic Acid, ASA, Aspergum, EcotrinGiven PO | Drug | Arm I (continuous aspirin), Arm II (intermittent aspirin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (continuous aspirin), Arm II (intermittent aspirin) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | Arm II (intermittent aspirin) |
Primary outcome
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
Time frame: Baseline to 12 weeks (End-of-Intervention)
Change in 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.
9 secondary outcomes
Changes in Urine Leukotriene E4 (LTE(4)) Levels
Time frame: Baseline to 12 weeks (End-of-Intervention)
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
Time frame: Baseline to 12 weeks (End-of-Intervention)
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Time frame: Up to 2 weeks post-treatment
Gender Effect on Smoking-related Gene Expression Signature Score
Time frame: Baseline to 12 weeks (End-of-Intervention)
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
Time frame: Baseline to 12 weeks (End-of-Intervention)
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Time frame: Baseline to 1 week post-intervention
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Time frame: Baseline to 1 week post-intervention
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
Time frame: Baseline to 12 weeks
Change in Buccal Cells Via Karyometric Analysis
Time frame: Baseline to up to one week post-intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda Garland principal investigator
The University of Arizona Medical Center-University Campus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin and Laboratory Biomarker Analysis in people with Lung Carcinoma and Tobacco Use Disorder, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium (time frame: Baseline to 12 weeks (End-of-Intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.