Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

• ClinicalTrials.gov Identifier: NCT02965703
• Recruitment Status: Active, not recruiting
• First Posted: November 17, 2016
• Last Update Posted: April 6, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

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 disease	Intervention/treatment	Phase
Colorectal Adenoma	Drug: Aspirin; Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration	Phase 2

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 (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 (Clinical Trial)
• 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: January 16, 2018
• Actual Primary Completion Date: December 22, 2021
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/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) [ Time Frame: 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 [ 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.
2. Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) assessed 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.
3. Fecal occult blood test assessed in 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.
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 [ 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.
5. Abundance of Escherichia coli and fusobacterium assessed by rectal swabs [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Tennessee

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Qi Dai; Northwestern University

  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

Study Protocol and Statistical Analysis Plan  [PDF] February 2, 2021

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02965703
• Other Study ID Numbers: NCI-2016-01642; NCI-2016-01642 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); N01-CN-2012-00035; NCI2015-06-01 ( Other Identifier: Northwestern University ); NWU2015-06-01 ( Other Identifier: DCP ); N01CN00035 ( U.S. NIH Grant/Contract ); P30CA060553 ( U.S. NIH Grant/Contract )
• First Posted: November 17, 2016
• Last Update Posted: April 6, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Aspirin; Adenoma; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics