Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Ratio of Cell Proliferation to Apoptosis Biomarkers (Ki67 Index and BAX Index)
研究概览
简要总结
This phase IIa trial studies how well aspirin works in preventing colorectal cancer in patients with colorectal adenoma. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To test for the equivalency of the two aspirin schedules.
SECONDARY OBJECTIVES:
I. To evaluate the effects of aspirin treatments on:
Ia. The ratio of cell proliferation (Ki-67)/apoptosis (TUNEL) in rectal biopsies; Ib. The ratio of cell proliferation (Ki-67)/necroptosis (pMLKL) in rectal biopsies; Ic. Fecal occult blood test (measures of adverse events) as measured by stool samples.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of colorectal adenoma of any grade
- •Age >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of aspirin in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- •Leukocytes >= 3,000/microliter
- •Absolute neutrophil count >= 1,500/microliter
- •Platelets >= 150,000/microliter
- •Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN
- •Creatinine =< 1.5 x institutional ULN
- •Blood hemoglobin >= 12.0 g/dL
- •Alkaline phosphatase =< 1.5 x institutional ULN
- •Blood urea nitrogen (BUN) =< 40 mg/dL
- •Estimated glomerular filtration rate (eGFR) >= 45 mL/min
- •Negative fecal occult blood test
- •The effects of aspirin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men 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
排除标准
- •Current (within three weeks of randomization) or planned use during the study intervention of the following:
- •Aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or COX-2 inhibitors
- •Anticoagulants, anti-platelet agents, or corticosteroids
- •Ethanol consumption > 1 standard drinks/day for women, or > 2 standard drinks/day for men
- •Methotrexate (MTX)
- •Study participants will be instructed to use Tylenol or some other non-excluded agent to treat common ailments (i.e. headache/minor aches and pains)
- •History of
- •Any invasive malignancy within the past 2 years, with the exception of non-melanoma skin cancer
- •Chronic renal diseases or liver cirrhosis
- •Diseases such as anemia, peptic ulcer, gastrointestinal bleeding, active colitis and inflammatory bowel disease
- •Hemorrhagic stroke or uncontrolled hypertension
- •Participants may not be receiving any other investigational agents
- •History of allergic reactions or intolerance attributed to aspirin or compounds of similar chemical or biologic composition
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
- •Women who are pregnant or breastfeeding; pregnant women are excluded from this study because aspirin has the potential for abortifacient effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with aspirin, breastfeeding should be discontinued if the mother is treated with aspirin
研究组 & 干预措施
Arm III (placebo)
Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm II (aspirin, placebo)
Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Rectal Biopsy (Procedure)
Arm II (aspirin, placebo)
Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Placebo Administration (Other)
Arm III (placebo)
Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Placebo Administration (Other)
Arm II (aspirin, placebo)
Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm I (aspirin)
Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (aspirin)
Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm II (aspirin, placebo)
Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (aspirin)
Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Rectal Biopsy (Procedure)
Arm III (placebo)
Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm III (placebo)
Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Rectal Biopsy (Procedure)
Arm I (aspirin)
Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Aspirin (Drug)
Arm II (aspirin, placebo)
Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity. Patients also undergo collection of blood, urine, stool, rectal swab samples, and rectal biopsies throughout the trial.
干预措施: Aspirin (Drug)
结局指标
主要结局
Ratio of Cell Proliferation to Apoptosis Biomarkers (Ki67 Index and BAX Index)
时间窗: Baseline to end of intervention up to 12 weeks
Change in the ratio of proliferation to apoptosis biomarkers (Ki67 density index: BAX density index, measured continuously after IHC staining) in colorectal mucosa of compliant participants
次要结局
- Ratio of Cell Proliferation (Ki-67)/Apoptosis (TdT-mediated dUTP Nick End Labeling [TUNEL]) in Rectal Biopsies(Baseline to end of intervention up to 12 weeks)
- Ratio of Cell Proliferation (Ki-67)/Necroptosis (MLKL) in Rectal Biopsies(Baseline to end of intervention up to 12 weeks)
- Fecal Occult Blood Test (Measures of Adverse Events) as Measured by Stool Samples(Baseline to end of intervention up to 12 weeks.)