Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

Colorectal Adenoma Clinical Trial

Official title:

Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02965703
• Other study ID #: NCI-2016-01642
• Secondary ID: NCI-2016-01642N0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 16, 2018
• Est. completion date: July 31, 2024

Study information

• Verified date: October 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 81
• Est. completion date: July 31, 2024
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenoma
• Colorectal Adenoma

Intervention

Drug:
• Aspirin
Given PO

Procedure:
• Biospecimen Collection
Undergo collection of blood, urine, stool, and rectal swab samples

Other:
• Placebo Administration
Given PO
• Questionnaire Administration
Ancillary studies

Procedure:
• Rectal Biopsy
Undergo rectal biopsy

Locations

Country	Name	City	State
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	COX-2 in rectal biopsies	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
Other	BCL2-Associated X Protein (BAX) in rectal biopsies	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
Other	Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) in rectal biospies	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
Other	Joint index of COX-2 with Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) expression in rectal biopsies	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
Other	Joint index of BAX with TRPM7 expression in rectal biopsies	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
Other	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	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
Other	Abundance of Escherichia coli and Fusobacterium and other microbiota in rectal swabs	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
Primary	Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index)		Up to 3 months
Secondary	Ratio of cell proliferation (Ki-67)/apoptosis (TdT-mediated dUTP nick end labeling [TUNEL]) in rectal biopsies	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
Secondary	Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) in rectal biopsies	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
Secondary	Fecal occult blood test (measures of adverse events) as measured by stool samples	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