A Randomized Phase II Trial of Low Dose Aspirin Versus Placebo in High-Risk Individuals With CT-Detected Subsolid Lung Nodules
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 2
- 主要终点
- Change in the Sum of Longest Diameters of Baseline Target Nodules (Person-specific Analysis)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm I (acetylsalicylic acid)
Patients receive acetylsalicylic acid PO QD for 12 months.
干预措施: Aspirin (Drug)
Arm I (acetylsalicylic acid)
Patients receive acetylsalicylic acid PO QD for 12 months.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients receive placebo PO QD for 12 months.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients receive placebo PO QD for 12 months.
干预措施: Placebo (Other)
结局指标
主要结局
Change in the Sum of Longest Diameters of Baseline Target Nodules (Person-specific Analysis)
时间窗: Twelve-month treatment
Difference (12 month-baseline) in the sum of longest diameters of baseline target nodules.
次要结局
- Change in Lesion Volume(Baseline to 1 year)
- Change in the Sum of Baseline Target Nodules Diameters (Per Nodules Analysis)(Baseline up to 1 year)
- Change in Lesion Density(Baseline up to 1 year)
- Modulation of Thromboxane B2(Baseline up to 1 year)
- Modulation of Leukotriene E4 (Normalized to Urinary Creatinine Concentration)(Baseline up to 1 year)
- Modulation of High Sensitive CRP(Baseline up to 1 year)
- Modulation of Prostaglandin E Metabolites (Normalized to Urinary Creatinine Concentration)(Baseline up to 1 year)
- Modulation of miRNA Prediction Risk Score(Baseline up to 1 year)