- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02965703
Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma
Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
Study Overview
Status
Conditions
Detailed Description
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.
EXPLORATORY OBJECTIVES:
I. To evaluate the effects of aspirin treatments on:
Ia. Cyclooxygenase-2 (COX-2) in rectal biopsies; Ib. Bcl-2-like protein 4 (BAX) in rectal biopsies; Ic. Transient receptor potential cation channel subfamily M member (7TRPM7) in rectal biopsies; Id. Joint index of COX-2 with TRPM7 expression in rectal biopsies; Ie. Joint index of TRPM7 with BAX in rectal biopsies; If. Methylation assays using the MethylationEPIC BeadChip to identify methylation biomarkers in genes (i.e. CDKN2A [cell cycle regulation], MGMT [deoxyribonucleic acid (DNA) repair], DAPK1 [apoptosis], CDH1 [cell invasion], WNT16 [Wnt pathway] and RASSF1 [RAS signaling]) involved in colorectal carcinogenesis, and other epigenome-wide methylation biomarkers as measured in rectal biopsies; Ig. Metagenomics analysis to measure abundance of Escherichia coli (E. coli) and Fusobacterium and other microbiota in rectal swabs.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive aspirin orally (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.
ARM II: 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.
ARM III: 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.
After completion of study, patients are followed up at 1 month.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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
- Gingko
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Given PO
Other Names:
Ancillary studies
Undergo collection of blood, urine, stool, and rectal swab samples
Other Names:
Undergo rectal biopsy
Other Names:
|
Experimental: 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.
|
Given PO
Other Names:
Ancillary studies
Given PO
Undergo collection of blood, urine, stool, and rectal swab samples
Other Names:
Undergo rectal biopsy
Other Names:
|
Placebo Comparator: 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.
|
Ancillary studies
Given PO
Undergo collection of blood, urine, stool, and rectal swab samples
Other Names:
Undergo rectal biopsy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index)
Time Frame: Up to 3 months
|
Up to 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ratio of cell proliferation (Ki-67)/apoptosis (TdT-mediated dUTP nick end labeling [TUNEL]) in rectal biopsies
Time Frame: Up to 12 weeks
|
All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes).
Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars.
Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context.
Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.
|
Up to 12 weeks
|
Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) in rectal biopsies
Time Frame: Up to 12 weeks
|
All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes).
Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars.
Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context.
Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.
|
Up to 12 weeks
|
Fecal occult blood test (measures of adverse events) as measured by stool samples
Time Frame: Up to 12 weeks
|
All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes).
Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars.
Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context.
Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.
|
Up to 12 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
COX-2 in rectal biopsies
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre- and post-treatment values will beexamined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
BCL2-Associated X Protein (BAX) in rectal biopsies
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre- and post-treatment values will be examined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) in rectal biospies
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre-and post-treatment values will beexamined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
Joint index of COX-2 with Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) expression in rectal biopsies
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre-and post-treatment values will be examined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
Joint index of BAX with TRPM7 expression in rectal biopsies
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre-and post-treatment values will be examined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
Methylation in CDKN2A (cell cycle regulation), MGMT (deoxyribonucleic acid [DNA] repair), DAPK1 (apoptosis), CDH1 (cell invasion), WNT16 (Wnt pathway), and RASSF1 (RAS signaling) assessed by pyrosequencing method
Time Frame: At baseline, 9, and 12 weeks
|
All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes).
Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars.
Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context.
Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.
|
At baseline, 9, and 12 weeks
|
Abundance of Escherichia coli and Fusobacterium and other microbiota in rectal swabs
Time Frame: At baseline, 9, and 12 weeks
|
Will be summarized using descriptive statistics including means and standard deviations or medians and interquartile range, as well as graphical methods such as "spaghetti plots" that depict change patterns over time.
Distributions of each marker will be examined, and values may be transformed as needed to stabilize the variance or satisfy the normality assumption.
Correlation between biomarkers, and between pre-and post-treatment values will be examined using scatterplots with overlayed smoother plots for ease of visual interpretation.
|
At baseline, 9, and 12 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Qi Dai, Northwestern University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Adenoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Aspirin
Other Study ID Numbers
- NCI-2016-01642 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA060553 (U.S. NIH Grant/Contract)
- N01-CN-2012-00035
- N01CN00035 (U.S. NIH Grant/Contract)
- NCI2015-06-01 (Other Identifier: Northwestern University)
- NWU2015-06-01 (Other Identifier: DCP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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