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

• ClinicalTrials.gov Identifier: NCT02169271
• Recruitment Status: Completed
• First Posted: June 23, 2014
• Results First Posted: May 21, 2020
• Last Update Posted: May 21, 2020
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: June 19, 2014
• First Posted Date: June 23, 2014
• Results First Submitted Date: December 20, 2019
• Results First Posted Date: May 21, 2020
• Last Update Posted Date: May 21, 2020
• Actual Study Start Date: November 21, 2014
• Actual Primary Completion Date: July 13, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2020)

Change in the Sum of Longest Diameters of Baseline Target Nodules (Person-specific Analysis) [ Time Frame: Twelve-month treatment ]

Difference (12 month-baseline) in the sum of longest diameters of baseline target nodules.

Original Primary Outcome Measures (submitted: June 19, 2014)

Difference of the sum of longest diameters of subsolid (non-solid or partially solid) lung nodules [ Time Frame: At 1 year ]

A two-sided paired t-test will be used to compare the average change in the dimension of sub-solid nodules in the aspirin group compared to the placebo group.

Current Secondary Outcome Measures (submitted: May 6, 2020)

• Change in the Sum of Baseline Target Nodules Diameters (Per Nodules Analysis) [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in the sum of baseline target nodules diameters
• Change in Lesion Volume [ Time Frame: Baseline to 1 year ]
  Difference (12 month-baseline) in lesion volume
• Change in Lesion Density [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in lesion density
• Modulation of Thromboxane B2 [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in biomarker concentration
• Modulation of Prostaglandin E Metabolites (Normalized to Urinary Creatinine Concentration) [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in biomarker concentration
• Modulation of Leukotriene E4 (Normalized to Urinary Creatinine Concentration) [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in biomarker concentration
• Modulation of High Sensitive CRP [ Time Frame: Baseline up to 1 year ]
  Difference (12 month-baseline) in biomarker concentration
• Modulation of miRNA Prediction Risk Score [ Time Frame: Baseline up to 1 year ]
  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).

Original Secondary Outcome Measures (submitted: June 19, 2014)

• Evaluation of response according to modified RECIST criteria [ Time Frame: Up to 1 year ]
  The per-lesion analysis and per-subject analysis will be done according to modified RECIST criteria. In case of multiple lesions, treatment will be considered successful when a complete response or partial response occurs according to modified RECIST criteria, while treatment will be considered a failure when progression of disease or stable disease occurs according to the same criteria.
• Change in the number and size of non target lesions [ Time Frame: Baseline to 1 year ]
  All tests will be two-sided and considered significant at the 5% level.
• Nodule density measured by quantitative changes in mean and maximum Hounfields Unit [ Time Frame: Baseline to 1 year ]
  All tests will be two-sided and considered significant at the 5% level.
• Sensitivity of micro ribonucleic acid (miRNA) to identify patients with ground glass opacities (GGO) or with partially solid nodules and predict aspirin treatment response [ Time Frame: Up to 1 year ]
  All tests will be two-sided and considered significant at the 5% level.
• Specificity of miRNA to identify patients with GGO or with partially solid nodules and predict aspirin treatment response [ Time Frame: Up to 1 year ]
  All tests will be two-sided and considered significant at the 5% level.
• Accuracy of miRNA to identify patients with GGO or with partially solid nodules and predict aspirin treatment response [ Time Frame: Up to 1 year ]
  All tests will be two-sided and considered significant at the 5% level.
• Biomarker analysis [ Time Frame: Up to 1 year ]
  Will include the modulation of high sensitivity-C-reactive protein (hs-CRP) as marker of inflammation, 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 metabolite (PGEM) and leukotriene E4 (LTE4) normalized to urinary creatinine concentration. Serum thromboxane B2 (TXB2) will be determined as a measure of compliance. Results will be compared between the two treatment arms (aspirin and placebo).
• Tolerability, defined by the incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 13 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Acetylsalicylic Acid Compared to Placebo in Treating High-Risk Patients With Subsolid Lung Nodules
• Official Title: A Randomized Phase II Trial of Low Dose Aspirin Versus Placebo in High-Risk Individuals With CT-Detected Subsolid Lung Nodules
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Current Smoker
• Former Smoker
• Multiple Pulmonary Nodules
• Tobacco Use Disorder

Intervention

• Drug: Aspirin
  Given PO
  Other Names:

  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Other: Placebo
  Given PO
  Other Names:

  • placebo therapy
  • PLCB
  • sham therapy

Study Arms

• Experimental: Arm I (acetylsalicylic acid)
  Patients receive acetylsalicylic acid PO QD for 12 months.
  Interventions:

  • Drug: Aspirin
  • Other: Laboratory Biomarker Analysis
• Placebo Comparator: Arm II (placebo)
  Patients receive placebo PO QD for 12 months.
  Interventions:

  • Other: Laboratory Biomarker Analysis
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2020): 109
• Original Estimated Enrollment (submitted: June 19, 2014): 128
• Actual Study Completion Date: February 14, 2020
• Actual Primary Completion Date: July 13, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, United States

Administrative Information

• NCT Number: NCT02169271
• Other Study ID Numbers: NCI-2014-01311; NCI-2014-01311 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); IEO-833/13F; HHSN261201200034I; EIO 833/13F; 2013-004862-32; TO-RFP A; N01-CN-2012-00034; IEO 833/13F (IEO37); MDACC: 2013-0732; IEO 37; 2013-0732 ( Other Identifier: M D Anderson Cancer Center ); MDA2013-01-01 ( Other Identifier: DCP ); N01CN00034 ( U.S. NIH Grant/Contract ); P30CA016672 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Cancer Institute (NCI)
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bernardo Bonanni; M.D. Anderson Cancer Center

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2020