Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

PRIMARY OBJECTIVES:

I. To test for the equivalency of the two aspirin schedules.

SECONDARY OBJECTIVES:

I. To evaluate the effects of aspirin treatments on the ratio of cell proliferation
(Ki-67)/apoptosis (TUNEL) in rectal biopsies.

II. To evaluate the effects of aspirin treatments on the ratio of cell proliferation
(Ki-67)/necroptosis (MLKL) in rectal biopsies.

III. To evaluate the effects of aspirin treatments on fecal occult blood test (measures of
adverse events) as measured by stool samples.

IV. To evaluate the effects of aspirin treatments on 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.

V. To evaluate the effects of aspirin treatments on colorectal mucosal nanoscale cellular
structural changes measured by PWS (partial wave spectroscopy) obtained through rectal
brushings.

VI. To evaluate the effects of aspirin treatments on abundance of E. coli and Fusobacterium
in rectal swabs.

VII. 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.

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.

ARM III: Patients receive placebo PO daily for 12 weeks.

After completion of study, patients are followed up at 6 months.

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 within normal institutional limits

- 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