ASPirin Intervention for the REDuction of Colorectal Cancer Risk

This research study, is investigating the use of aspirin as a potential chemopreventive agent
to reduce risk of colorectal cancer. Within the gastroenterology practice of Massachusetts
General Hospital (MGH), we will conduct a prospective, double-blind, placebo-controlled,
randomized clinical trial to measure the effects of daily low-dose (81 mg/day) and
standard-dose (325 mg/day) aspirin on urine, plasma, stool, and tissue biomarkers associated
with colorectal cancer.

Aspirin is part of the non-steroidal anti-inflammatory drug (NSAID) family, which are drugs
routinely used for their pain-killing (analgesic), fever-reducing (antipyretic), or
anti-inflammatory properties. Most NSAIDs are available as over-the-counter formulations.
Substantial evidence has conclusively demonstrated that aspirin reduces the risk of
colorectal neoplasia, yet there remains uncertainty surrounding its mode of action. Aspirin
has already been established to reduce the risk of cardiovascular disease. Prospective
studies as well as randomized clinical trials demonstrate that aspirin reduces the risk of
precancerous polyps and colorectal cancer.

Inclusion Criteria:

- Underwent screening or surveillance colonoscopy at MGH within the last 9 months with
removal of at least one adenoma.

- Age 18-80 years.

- This study will only include adult participants because colorectal carcinogenesis in
children is more likely to be related to a cancer predisposition syndrome with
distinct biological mechanisms compared with sporadic colorectal cancer in adults.
Patients over age 80 will not be enrolled since the benefits and risks of a daily
aspirin regimen over the age of 80 have not yet been well-characterized.

- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

- Not currently taking aspirin (any dose) within the last 6 months.

- The effects of aspirin on the developing human fetus are unknown. For this reason,
women of child-bearing potential 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 she is participating in this study, she should inform her treating physician
immediately.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID) at any dose at
least three times a week during the two months prior to randomization.

- Diagnosis of inflammatory bowel disease, liver or kidney disease, bleeding diathesis

- Any prior diagnosis of gastrointestinal cancer (including esophageal, small intestine,
colon, pancreatic), or any diagnosis of other cancers (with the exception of non-
melanoma skin) in which there has been any active treatment within the last three
years

- Participants who are receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to aspirin.

- Known diagnosis of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis
Colorectal Cancer (HNPCC, Lynch Syndrome).

- Any adenoma that was not completely removed during previous colonoscopy.

- History of aspirin intolerance, bleeding diathesis, peptic ulcer or gastrointestinal
bleed, endoscopic complications, or contraindication to colonoscopy.

- Inability or unwillingness to abstain from non-protocol use of aspirin or NSAIDs or to
provide blood, urine, or stool samples or colon biopsies during the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant or breastfeeding.

- Pregnant women are excluded from this study because aspirin is an FDA Category D agent
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with aspirin, breastfeeding should be discontinued if the
mother is treated with aspirin.

- Participant must be able to swallow pills.

- Participant is taking any anticoagulant agent (e.g. warfarin) or antiplatelet agent
(e.g. clopidogrel).