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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
81
Given PO
Undergo collection of blood, urine, stool, and rectal swab samples
Given PO
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Ratio of Cell Proliferation to Apoptosis Biomarkers (Ki67 Index and BAX Index)
Change in the ratio of proliferation to apoptosis biomarkers (Ki67 density index: BAX density index, measured continuously after IHC staining) in colorectal mucosa of compliant participants
Time frame: Baseline to end of intervention up to 12 weeks
Ratio of Cell Proliferation (Ki-67)/Apoptosis (TdT-mediated dUTP Nick End Labeling [TUNEL]) in Rectal Biopsies
Change in the ratio of proliferation to apoptosis biomarkers (Ki67 density index: TUNEL density index, measured continuously after IHC staining) in colorectal mucosa of compliant participants.
Time frame: Baseline to end of intervention up to 12 weeks
Ratio of Cell Proliferation (Ki-67)/Necroptosis (MLKL) in Rectal Biopsies
Change in the ratio of proliferation to necroptosis biomarkers (Ki67 density index: pMLKLdensity index, measured continuously after IHC staining) in colorectal mucosa of compliant participants
Time frame: Baseline to end of intervention up to 12 weeks
Fecal Occult Blood Test (Measures of Adverse Events) as Measured by Stool Samples
The number of participants who started intervention and had a positive fecal occult blood test result
Time frame: Baseline to end of intervention up to 12 weeks.
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Ancillary studies
Undergo rectal biopsy