PREPARE: PRevention Using EPA Against coloREctal Cancer

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04216251

Collaborator

National Institutes of Health (NIH) (NIH)

Enrollment

Location

Arm

31.4

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Adenoma Colorectal Cancer Endoscopic Surgery Eicosapentaenoic Acid Gastrointestinal Microbiome	Drug: AMR101	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

PREPARE: PRevention Using EPA Against coloREctal Cancer

Actual Study Start Date :

Mar 19, 2020

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMR101 Study procedures include screening for eligibility and study treatment including ARM101 Lifestyle questionnaire, Nutritional survey. Flexible sigmoidoscopy (24 biopsies of normal colorectal mucosa, one stool sample),blood, evaluations, and follow up visits. - AMR101-oral predetermined protocol dosage, daily for a minimum of 8 weeks and maximum of 12 weeks	Drug: AMR101 AMR101-oral predetermined protocol dosage, daily for a minimum of 8 weeks and maximum of 12 weeks Other Names: VASCEPA

Arm

Intervention/Treatment

Experimental: AMR101

Study procedures include screening for eligibility and study treatment including ARM101 Lifestyle questionnaire, Nutritional survey. Flexible sigmoidoscopy (24 biopsies of normal colorectal mucosa, one stool sample),blood, evaluations, and follow up visits. - AMR101-oral predetermined protocol dosage, daily for a minimum of 8 weeks and maximum of 12 weeks

Drug: AMR101

AMR101-oral predetermined protocol dosage, daily for a minimum of 8 weeks and maximum of 12 weeks

Other Names:

VASCEPA

Outcome Measures

Primary Outcome Measures

The change in the marine omega-3 polyunsaturated fatty acid (MO3PUFA) composition in colorectal tissues as a result of the AMR101 treatment for at least 28 days. [2 years after study completion]
The effect of daily 4-gram AMR101 treatment on MO3PUFA composition in colorectal tissue will be measured through the extraction of fatty acid with gas chromatography-mass spectrometry from the biopsy tissue.

Secondary Outcome Measures

The change in the gut microbiome composition and function between pre- and post- AMR101 treatment period. [2 years after study completion]
Metagenomic and metatranscriptomic sequencing of microbial DNA and RNA on pre- and post-treatment stool samples will be performed to examine the biomolecular mechanisms by which gut microbial activity may be altered or respond to AMR101 treatment.

Other Outcome Measures

The change in stool metabolomics between pre- and post- AMR101 treatment period. [2 years after study completion]
Non-targeted global metabolomics and lipidomics analysis on pre- and post-treatment stool samples will be performed to examine the changes in the stool metabolite profile as a result of the AMR101 treatment.
The change in gene expression profile of colorectal tissue between pre- and post- AMR101 treatment period. [2 years after study completion]
RNA-seq analysis to profile gene expression in the mucosal tissue collected before and after AMR101 treatment will be performed to examine whether the AMR101 treatment reduces the gene expression of inflammatory cytokines, chemokines (e.g., TNFα, IL6 and CCL2), and immunosuppressive factors.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.