PRevention Using EPA Against coloREctal Cancer
PRevention Using EPA Against coloREctal Cancer
This research study is evaluating the effect of AMR101 as a possible chemopreventive agent to
 reduce risk of colorectal cancer in individuals with a history of colorectal adenoma.

 - The name of the study drug involved in this study is:

 -- AMR101 (VASCEPA).
This prospective, single-arm, research study evaluating the effect of AMR101, as a
 chemopreventive agent to reduce risk of colorectal cancer in individuals with a history of
 colorectal adenoma.

 -  AMR101 is made of marine omega-3 fatty acid, which is a family of natural substances
 found in the oil of certain fish, such as salmon and mackerel. Marine omega-3 fatty acid
 cannot be produced in sufficient amount by the human body and has to be obtained through
 diet or supplemented to maintain normal function in the body.

 -  The U.S. Food and Drug Administration (FDA) has not approved AMR101 as a treatment for
 any disease.

 -  AMR101 is commercially available in the US as VASCEPA (icosapent ethyl)

 -  The research study procedures include screening for eligibility and study treatment
 including evaluations and follow up visits, including:

 -  Lifestyle questionnaire,

 -  Nutritional survey

 -  Flexible sigmoidoscopy (24 biopsies of normal colorectal mucosa, one stool sample)

 -  Blood samples,

 -  AMR101 administered daily, orally for 8-12 weeks and it is expected 80 participants will
 take part.
Inclusion Criteria:

 Participants must meet the following criteria on screening examination to be eligible to
 participate in the study:

 -  Underwent screening or surveillance colonoscopy 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
 AMR101 over the age of 80 have not yet been well-characterized.

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

 -  The effects of AMR101 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.

 -  Subjects must be able and willing to follow study procedures and instructions.

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

 Exclusion Criteria:

 Participants who exhibit any of the following conditions at screening will not be eligible
 for admission into the study

 -  Currently using or have used any fish oil supplement at any dose more than once per
 week within the last month

 -  Regularly consuming more than three servings of fish per week.

 -  History of allergic reactions attributed to fish or compounds of similar chemical or
 biologic composition to omega-3 fatty acid.

 -  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
 nonmelanoma skin) in which there has been any active treatment within the last three
 years.

 -  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.

 -  Known bleeding tendency/condition (e.g. von Willebrand disease) or history of peptic
 ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to
 colonoscopy.

 -  Current use of anticoagulant therapies, including Heparin, Warfarin, Dalteparin
 sodium,Bivalirudin, Argatroban, Lepirudin, Heparin Sodium, Heparin/Dextrose, and an
 unwillingness or inability to discontinue anticoagulants.

 -  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.

 -  Inability or unwillingness to abstain from non-protocol use of fish oil supplements or
 to provide blood or stool samples or colon biopsies during the study.

 -  Participants who are receiving any other investigational agents.

 -  Inability or unwillingness to swallow pills.

 -  Pregnant or breastfeeding. The effects of AMR101 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. Similarly, lactating women are excluded from this
 study because there is an unknown but potential risk of adverse events in nursing
 infants secondary to treatment of the mother with AMR101. Consequently, breastfeeding
 should be discontinued if the mother is enrolled on the study.

 -  Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or
 acute or chronic hepatitis B infection. Participants with these infections are
 ineligible because they are at increased risk of significant complications in the
 perioperative period, and because fresh tissue from patients with these infections
 cannot be harvested for research purposes, per institutional policy. Appropriate
 studies will be undertaken in participants receiving combination antiretroviral
 therapy when indicated.