Lung cancer increased risk in current or former heavy smokers, with CT SCAN screen detected subsolid lung nodules (Cosmos Project) MedDRA version: 17.0 Level: PT Classification code 10025065 Term: Lung carcinoma cell type unspecified recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cardioaspirin
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Istituto Europeo Oncologia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Asymptomatic current or former smokers (having stopped within the last 20 years), • Age > 50 years (risk of lung cancer in subjects under 50 is low thus screening is not indicated by actual international guidelines). • Smoking history > 20 pack/years, subjects must be included in an ongoing annual screening with low dose CT scan (Cosmos 1 or Cosmos 2). • Subjects must have subsolid (non solid or partially solid) nodules with size between 4 and 10 mm with any Volume Doubling Time (VDT) 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 ld-CT • ECOG performance status =1 (Karnofsky =70%; see Appendix A) • Participants must have normal organ and marrow function • Ability to understand and the willingness to sign a written informed consent document. • Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: • Subjects with chronic treatment (at least twice/week for more than 3 months) with Aspirin or other NSAIDs (representing 15% of Cosmos 1 population) • History of allergic reactions attributed to compounds of similar chemical or biological composition to aspirin, NSAIDs, COX2 inhibitors • Invasive malignancy (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization • History of therapeutic doses of anticoagulants • 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 because Aspirin is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Aspirin, breastfeeding should be discontinued if the mother is treated with Aspirin • Participants with bleeding diathesis, history of gastric/duodenal ulcers, NSAID-precipitated bronchospasm, patients unwilling or unable to limit alcohol consumption to i.e. = 2 alcohol drinks a day. • Participants who in the opinion of the PI will be at higher risk of ASA-related complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Size reduction of pulmonary nodules evaluated with the by subject analysis. For single nodules clinically meaningful reduction of 30% or more of the larger diameter will be considered remission after one year of treatment. The growth of 20% or more with a minimum of 2mm will be considered progression. In the case of multiple lesions will be considered the sum of the maximum diameters of all nodules target, using the same parameters to define remission or progression (respectively 30% reduction and 20% increase).;Timepoint(s) of evaluation of this end point: 12 months;Main Objective: To evaluate the effect on the diameter and the number of pulmonary non-solid or partially solid nodules, after one year treatment in an for subject analysis.;Secondary Objective: Secondary objective of the study will be the modulation of biological markers after treatment and the correlation of these findings with modification of lung nodules diameters. In particular we will evaluate the effect of Aspirin on a signature of serum microRNA correlated to subsolid nodules. 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 RECIST criteria. Modulation of ultrasensitive circulating hs-CRP, the evaluation of urinary cotinine as marker of tobacco exposure and investigation of the potential effect of aspirin according to its concentration, the measurement of urinary prostaglandin metabolites (PGEM) and leukotriene (LTE4), both normalized normalized to urinary creatinine concentration. Serum concentration of thromobxane B2 (TXB2) will be determined as a measure of compliance. Tolerability of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be the modulation of biological markers after treatment and the correlation of these findings with modification of lung nodules diameters. In particular we will evaluate the effect of Aspirin on a signature of serum miRNA correlated to subsolid nodules. Other secondary endpoints will be the per-lesion analysis including the evaluation of lung nodule density before and after treatment and the number and size of non target lesions. Additional biomarkers will include the modulation of hs-CRP, the evaluation of urinary cotinine as marker of tobacco exposure and investigation of the potential effect of aspirin according to its concentration, the measurement of urinary prostaglandin metabolites (PGEM) and urine leukotriene E4 (LTE4) both normalized to urinary creatinine concentration. Serum concentration of thromboxane B2 (TXB2) will be determined as a measure of compliance. We will also evaluate the tolerability of Aspirin at dose of 100 mg/day.;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
Italy
Contacts
Public ContactUfficio studi clinici & Att. Regola
Istituto Europeo Oncologia
Outcome results
None listed