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

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.

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 ? 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