Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT02965703
Collaborator
(none)
81
Enrollment
1
Location
3
Arms
59.5
Anticipated Duration (Months)
1.4
Patients Per Site Per Month

Study Details

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Aspirin
  • Other: Laboratory Biomarker Analysis
  • Other: Placebo Administration
  • Other: Questionnaire Administration
Phase 2

Detailed Description

PRIMARY OBJECTIVE:
  1. 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 (MLKL) in rectal biopsies.

Ic. Fecal occult blood test (measures of adverse events) as measured by stool samples.

Id. 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, as measured in rectal biopsies.

Ie. Abundance of Escherichia (E.) coli and Fusobacterium in rectal swabs. II. To evaluate if the effects of aspirin arms may be modified by dietary intake of calcium as measured by the Food Frequency Questionnaire (FFQ).

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.

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.

ARM III: Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity.

After completion of study, patients are followed up at 1 month.

Study Design

Study Type:
Interventional
Actual Enrollment :
81 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
Actual Study Start Date :
Jan 16, 2018
Actual Primary Completion Date :
Dec 22, 2021
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I (aspirin)

Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity.

Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Questionnaire Administration
    Ancillary studies

    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.

    Drug: Aspirin
    Given PO
    Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Placebo Administration
    Given PO

    Other: Questionnaire Administration
    Ancillary studies

    Placebo Comparator: Arm III (placebo)

    Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity.

    Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Placebo Administration
    Given PO

    Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index) [Up to 3 months]

    Secondary Outcome Measures

    1. Ratio of cell proliferation (Ki-67)/apoptosis (TdT-mediated dUTP nick end labeling [TUNEL]) assessed in rectal biopsies [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.

    2. Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) assessed in rectal biopsies [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.

    3. Fecal occult blood test assessed in stool samples [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.

    4. 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 [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.

    5. Abundance of Escherichia coli and fusobacterium assessed by rectal swabs [Up to 9 months]

      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.

    6. Dietary intake of calcium measured by the Food Frequency Questionnaire [Up to 9 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of colorectal adenoma of any grade

    • 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Vanderbilt University/Ingram Cancer CenterNashvilleTennesseeUnited States37232

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Qi Dai, Northwestern University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02965703
    Other Study ID Numbers:
    • NCI-2016-01642
    • NCI-2016-01642
    • N01-CN-2012-00035
    • NCI2015-06-01
    • NWU2015-06-01
    • N01CN00035
    • P30CA060553
    First Posted:
    Nov 17, 2016
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022