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Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

Primary Purpose

Colorectal Adenoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Biospecimen Collection
Placebo Administration
Questionnaire Administration
Rectal Biopsy
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Adenoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vanderbilt University/Ingram Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm I (aspirin)

Arm II (aspirin, placebo)

Arm III (placebo)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index)

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
November 16, 2016
Last Updated
August 17, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02965703
Brief Title
Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma
Official Title
Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 16, 2018 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Adenoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (aspirin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (aspirin, placebo)
Arm Type
Experimental
Arm Description
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 Title
Arm III (placebo)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Acetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood, urine, stool, and rectal swab samples
Intervention Type
Other
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Procedure
Intervention Name(s)
Rectal Biopsy
Other Intervention Name(s)
Biopsy of Rectum
Intervention Description
Undergo rectal biopsy
Primary Outcome Measure Information:
Title
Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index)
Time Frame
Up to 3 months
Secondary Outcome Measure Information:
Title
Ratio of cell proliferation (Ki-67)/apoptosis (TdT-mediated dUTP nick end labeling [TUNEL]) in rectal biopsies
Description
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.
Time Frame
Up to 12 weeks
Title
Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) in rectal biopsies
Description
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.
Time Frame
Up to 12 weeks
Title
Fecal occult blood test (measures of adverse events) as measured by stool samples
Description
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.
Time Frame
Up to 12 weeks
Other Pre-specified Outcome Measures:
Title
COX-2 in rectal biopsies
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
BCL2-Associated X Protein (BAX) in rectal biopsies
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) in rectal biospies
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
Joint index of COX-2 with Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) expression in rectal biopsies
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
Joint index of BAX with TRPM7 expression in rectal biopsies
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
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
Description
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.
Time Frame
At baseline, 9, and 12 weeks
Title
Abundance of Escherichia coli and Fusobacterium and other microbiota in rectal swabs
Description
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.
Time Frame
At baseline, 9, and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qi Dai
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

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Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

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