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

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ClinicalTrials.gov Identifier: NCT02169271
Recruitment Status : Active, not recruiting
First Posted : June 23, 2014
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Current Smoker Former Smoker Multiple Pulmonary Nodules Tobacco Use Disorder Drug: Aspirin Other: Laboratory Biomarker Analysis Other: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized Phase II Trial of Low Dose Aspirin Versus Placebo in High-Risk Individuals With CT-Detected Subsolid Lung Nodules
Actual Study Start Date : November 21, 2014
Actual Primary Completion Date : July 13, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Arm I (acetylsalicylic acid)
Patients receive acetylsalicylic acid PO QD for 12 months.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for 12 months.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy




Primary Outcome Measures :
  1. Difference in sum of longest diameters of baseline target lesions in a person-specific analysis [ Time Frame: Baseline to 1 year ]
    Target lesions will be defined as non-solid or partially solid nodules. New lesions identified during follow-up satisfying the same criteria for the definition of target lesion will also be included in the analysis. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Nodule density measured by quantitative changes in mean and maximum Hounsfields Unit [ Time Frame: Baseline to 1 year ]
    All tests will be two-sided and considered significant at the 5% level.

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ? 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02169271


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Italy
European Institute of Oncology
Milano, Italy, 20141
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Bernardo Bonanni M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02169271     History of Changes
Obsolete Identifiers: NCT02135497
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 )
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
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Multiple Pulmonary Nodules
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics