Acetylsalicylic Acid Compared to Placebo in Treating High-Risk Patients With Subsolid Lung Nodules

Study Overview
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Brief Summary
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This randomized phase II trial studies acetylsalicylic acid compared to placebo in treating high-risk patients with subsolid lung nodules. A nodule is a growth or lump that may be malignant (cancer) or benign (not cancer). Chemoprevention is the use of drugs to keep cancer from forming or coming back. The use of acetylsalicylic acid may keep cancer from forming in patients with subsolid lung nodules.

Detailed Description
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PRIMARY OBJECTIVES: I. The evaluation of the effect of aspirin (acetylsalicylic acid) as a chemopreventive agent for lung cancer. SECONDARY OBJECTIVES: I. The modulation of biological markers after treatment and the correlation of these findings with modification of lung nodules diameters. II. The per-lesion analysis including the evaluation of lung nodule density before and after treatment, the number and size of non target lesions including solid nodules and evaluation of response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive acetylsalicylic acid orally (PO) once daily (QD) for 12 months. ARM II: Patients receive placebo PO QD for 12 months. After completion of study treatment, patients are followed up for 1 month.

Official Title
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A Randomized Phase II Trial of Low Dose Aspirin Versus Placebo in High-Risk Individuals With CT-Detected Subsolid Lung Nodules

Conditions
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Current Smoker, Former Smoker, Multiple Pulmonary Nodules, Tobacco Use Disorder

Intervention / Treatment
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* Drug: Aspirin
* Other: Laboratory Biomarker Analysis
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic current or former smokers (having stopped within the last 20 years) Smoking history >= 20 pack/years; subjects must be included in an ongoing annual screening with low dose CT scan or must have two consecutive CT outside the context of a screening program confirming subsolid nodules Subjects must have subsolid (non solid or partially solid) nodules with size between 4 and 10 mm with any volume doubling time (VDT) not candidate to surgical excision and/or subsolid (non solid or partially solid) nodule larger than 10 mm with VDT higher than 400 days and not candidate to surgical excision All nodules should be persistent at least after three months follow up with 1 dimension (1d)-CT; a reduction up to 15% of the diameter of the largest target nodule from the previous CT scan is allowed All current smokers should accept to receive support for smoking cessation Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Leukocytes >= 3,000/microliter Absolute neutrophil count >= 1,500/microliter Platelets >= 100,000/microliter Total bilirubin =< 2 x institutional upper limit of normal (ULN) and/or history of Gilbert's syndrome Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN Serum creatinine =< institutional ULN Women of child-bearing potential (from first menstruation to 1 year after last menstruation) 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 Ability to understand and the willingness to sign a written informed consent document Signed informed consent Exclusion Criteria: Subjects with chronic treatment (at least twice/week for more than 3 months) with aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) History of allergic reactions attributed to compounds of similar chemical or biological composition to aspirin, NSAIDs, cyclooxygenase-2 (COX2) inhibitors Invasive malignancy (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization; stage I-II invasive malignancies that were diagnosed more than 2 years prior to randomization and have been treated curatively are allowed as long as all treatment is finished at least 18 months prior to randomization History of therapeutic doses of anticoagulants including warfarin and low molecular weight heparin (e.g. for prior deep venous thrombosis and pulmonary embolisms) in the preceding year 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 Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with aspirin Individual may not be receiving any other investigational agents, antiplatelet agents (e.g. aspirin, clopidogrel [Plavix or others]), anticoagulants (e.g. heparin or heparinoids, Coumadin, or others), methotrexate, lithium Participants with bleeding diathesis, history of gastric/duodenal ulcers in the last 5 years, NSAID-precipitated bronchospasm, patients unwilling or unable to limit alcohol consumption to i.e. =< 3 alcohol drinks a day Participants who in the opinion of the principal investigator (PI) will be at higher risk of acetylsalicylic acid (ASA)-related complications Participants with known inability to adequately absorb oral medication

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (acetylsalicylic acid)<br>Patients receive acetylsalicylic acid PO QD for 12 months. | Drug: Aspirin<br>* Given PO<br>* Other names: Measurin;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO QD for 12 months. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Placebo<br>* Given PO<br>* Other names: sham therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Sum of Longest Diameters of Baseline Target Nodules (Person-specific Analysis) | Difference (12 month-baseline) in the sum of longest diameters of baseline target nodules. | Twelve-month treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Sum of Baseline Target Nodules Diameters (Per Nodules Analysis) | Difference (12 month-baseline) in the sum of baseline target nodules diameters | Baseline up to 1 year | 
| Change in Lesion Volume | Difference (12 month-baseline) in lesion volume | Baseline to 1 year | 
| Change in Lesion Density | Difference (12 month-baseline) in lesion density | Baseline up to 1 year | 
| Modulation of Thromboxane B2 | Difference (12 month-baseline) in biomarker concentration | Baseline up to 1 year | 
| Modulation of Prostaglandin E Metabolites (Normalized to Urinary Creatinine Concentration) | Difference (12 month-baseline) in biomarker concentration | Baseline up to 1 year | 
| Modulation of Leukotriene E4 (Normalized to Urinary Creatinine Concentration) | Difference (12 month-baseline) in biomarker concentration | Baseline up to 1 year | 
| Modulation of High Sensitive CRP | Difference (12 month-baseline) in biomarker concentration | Baseline up to 1 year | 
| Modulation of miRNA Prediction Risk Score | Difference (12 month-baseline) of the score on a scale (scale from -20 to +30 which measure the risk of lung cancer. Higher values indicate higher risk. A value<0 is considered negative, a value ≥0 positive for lung cancer). | Baseline up to 1 year |