Clinical trial: NCT04216251
Section: Alternatives
Subsections: 6. Will Being In This Study Benefit Me In Any Way?|7. What Are My Options?

We do not know if taking part in this study will benefit you. This study may help researchers learn information that could help people in the future.

Instead of being in this research study, you have other options which may include the following:
Receive standard treatment including follow-up colonoscopy at the appropriate surveillance interval as prescribed by your physician.  
Receive the same drugs, but not as part of a research study. Decide not to participate in this research study  
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BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 Participate in another research study.  
  
  
If you choose not to participate, are not eligible to participate, or withdraw from this research study, this will not affect your present or future care and will not cause any penalty or loss of benefits to which you are otherwise entitled. We encourage you to take some time to think this over, to discuss it with other people and your primary doctor, and to ask questions at any time.  
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Clinical trial: NCT04216251
Section: Confidentiality
Subsections: M. Confidentiality|O. Certificate Of Confidentiality (Coc)|Q. Privacy Of Protected Health Information (Hipaa Authorization)|2. Why Will Protected Information About Me Be Used Or Shared With Others?|3. Who Will Use Or Share Protected Health Information About Me?|4. With Whom Outside Of Df/Hcc May My Protected Health Information Be Shared?|5. For How Long Will Protected Health Information About Me Be Used Or Shared With Others?

We will take measures to protect the privacy and security of all your personal information, but we cannot guarantee complete confidentiality of study data. Medical information created by this research study may become part of your hospital medical record and may be forwarded to your primary doctor. Information that does not become part of your medical record will be stored in your study file. It may also become part of a research database. Participation in this study involves providing a specimen of your tissue; please know that if the research doctor leaves the institution, the research and the tissue might remain at the research doctor's current institute or might be transferred to another institution. The study team plans to publish the results of this research study and when we do, we may be asked to make the data we collect available to other researchers. We will not include information that identifies you in any publications or to the researchers who request the data to do additional research. Your de-dentified specimens or genetic data may also be placed into one or more publicly-accessible scientific databases. Through such databases, researchers from around the world will have access to de-identified samples or data for future research. There is a risk that de-identified research data that is shared with outside collaborators may be reidentified. When de-identified data and specimens are shared with outside collaborators agreements limit what the outside collaborators can do with the information to help prevent reidentification.

To help protect your privacy, we have been issued a Confidentiality Certificate from the National Institutes of Health (NIH). With this Certificate, the researchers on this study cannot be forced (for example, by court subpoena) to disclose information that may identify you in federal, state, or local civil, criminal, administrative, legislative or other proceedings. Disclosure will be necessary upon request of a United States federal or state government agency sponsoring the project that will be used for audit or program evaluation purposes or to meet the requirements of the federal Food and Drug Administration (FDA). You should understand that a Certificate of Confidentiality does not prevent you or a member of your family or even the research doctor from voluntarily releasing information about yourself or your involvement in this research. If an insurer, medical care provider, or employer learns about your participation, and obtains your consent to receive research information, then we cannot use the Certificate of Confidentiality to withhold this information. This means that you and your family must actively protect your own privacy. The Certificate of Confidentiality cannot be used to prevent disclosure to state or local authorities when there is a duty to report concerns of abuse, neglect, selfharm or a danger to others.

The Health Insurance Portability and Accountability Act (HIPAA) is a federal law that requires Dana-Farber/Harvard Cancer Center (DF/HCC) and its affiliated research doctors, health care providers, and physician network to protect the privacy of information that identifies you and relates to your past, present, and future physical and mental health conditions ("protected health information"). If you enroll in this research study, your "protected health information" will be used and shared with others as explained below.

The main reasons include the following:
To conduct and oversee the research described earlier in this form; To ensure the research meets legal, institutional, and accreditation requirements; To conduct public health activities (including reporting of adverse events or situations where you or others may be at risk of harm); and
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BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 To provide the study sponsor with information arising from an adverse event or other event that relates to the safety or toxicity of the drug(s) used in the study and for the purpose of this or other research relating the study drug(s) and their use in cancer; To better understand the diseases being studied and to improve the design of future studies; and, Other reasons may include for treatment, payment, or health care operations. For example, some medical information produced by this research study may become part of your hospital medical record because the information may be necessary for your medical care. (You will also be given a notice for use and sharing of protected health information.)

DF/HCC and its affiliated research doctors and entities participating in the research will use and share your protected health information. In addition, other DF/HCC offices that deal with research oversight, billing or quality assurance will be able to use and share your protected health information.

While all reasonable efforts will be made to protect the confidentiality of your protected health information, it may also be shared with the following entities:
Outside individuals or entities that have a need to access this information to perform functions relating to the conduct of this research such as analysis by outside laboratories on behalf of DF/HCC and its affiliates (for example, data storage companies, insurers, or legal advisors).  
The sponsor(s) of the study, its subcontractors, representatives, business partners, and its agent(s): Cancer Institute and the National Institutes of Health.  
Other research doctors and medical centers participating in this research, if applicable Federal and state agencies (for example, the Department of Health and Human Services, the Food and Drug Administration, the National Institutes of Health, and/or the Office for Human Research Protections), or Page 20 of 24  
  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 other domestic or foreign government bodies if required by law and/or necessary for oversight purposes. A qualified representative of the FDA and the National Cancer Institute may review your medical records.  
Hospital accrediting agencies A data safety monitoring board organized to oversee this research, if applicable Some who may receive your protected health information may not have to satisfy the privacy rules and requirements. They, in fact, may share your information with others without your permission.

There is no scheduled date at which your protected health information that is being used or shared for this research will be destroyed, because research is an ongoing process.
Clinical trial: NCT04216251
Section: Duration of Study Involvement
Subsections: 4. What Does This Research Study Involve And How Long Will It Last?

This research study involves intervention of AMR101 (VASCEPA) regimen (4 g/day) for 8-12 weeks with two study visits, including one prior to intervention and the other one after completion of the intervention.  
The names of the study drug involved in this study are/is:
A daily AMR101 (VASCEPA).  
AMR101 (icosapent ethyl) is a prescription medicine for adults to lower blood levels of triglycerides. It is supplied as a liquid-filled gel capsule for oral administration. The standard dose is 4 grams per day (administered as 8 halfgram capsules). Each 0.5-gram capsule of AMR101 contains 0.5 gram of icosapent ethyl, which is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). EPA possesses triglyceride-lowering and antiinflammatory activities and has been suggested to be beneficial for a variety of health outcomes in adults, including coronary heart disease, stroke, type 2 diabetes, depression, and inflammatory bowel disease, although the data are not univocal. Increasing evidence supports the anticancer effect of EPA. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits during which you will undergo a flexible sigmoidoscopy procedure, provide a blood draw, a urine sample, and complete a lifestyle questionnaire and a nutritional survey. Up to 24 mucosal biopsies will be taken, and a rectal brushing and stool specimen will also be collected. You will receive study treatment of AMR101 for a minimum of 8 weeks and will be followed for a maximum of 12 weeks. It is expected that about 80 people will take part in this research study. Information about you and your health is personal and private. Generally, it cannot be obtained without your written permission. By signing this form, you are providing that permission and your information may be obtained and used in Page 2 of 24  
  
accordance with this informed consent and as required or allowed by law. This means that researchers may obtain information regarding your past medical history, as well as specimens and samples from previous health care providers such as hospitals and labs.
Clinical trial: NCT04216251
Section: Participant's Rights
Subsections: 6. Statement Of Privacy Rights:

You have the right to withdraw your permission for the research doctors and participating DF/HCC entities to use or share your protected health information. We will not be able to withdraw all the information that already has been used or shared with others to carry out related activities such as oversight, or that is needed to ensure quality of the study. To withdraw your permission, you must do so in writing by contacting the researcher listed above in the section: "Whom do I contact if I have questions about the research study?"
You have the right to request access to your protected health information that is used or shared during this research and that is related to your treatment or payment for your treatment, but you may access this information only after the study is completed. To request this information, please contact the researcher listed above in the section: "Whom do I contact if I have questions about the research study?"
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Clinical trial: NCT04216251
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 5. What Are The Risks To Participating In This Study?|C. What Are The Risks Or Discomforts Of The Research Study?|Risks Associated With Flexible Sigmoidoscopy:|Risks Associated With Biopsies:|Risks Associated With Phlebotomy:|Reproductive Risks:|Risks Of Tissue Collection For Biobanking:|Non-Physical Risks:|E. What Are The Benefits Of This Research Study?|H. What Happens If I Am Injured Or Become Sick Because I Took Part In This Research Study?

There are risks to taking part in any research study. We want to make sure you know about a few key risks right now. There may also be rare, serious and potentially life-threatening side effects. More detailed information is provided in the "What are the risks or discomforts of the research study?" section. There is a risk that you could have side effects from the AMR101 drug. Some of the most common side effects associated with participating in the study that doctors know about are:
Arthralgia (or joint stiffness) associated with AMR101 treatment Dental pain and pain in the throat Mild to moderate gastrointestinal effects that include stomach pain, nausea, loss of appetite, constipation, or diarrhea.  
Perforation (or a hole) in the intestinal wall associated with flexible Sigmoidoscopy

There are risks to taking part in any research study. One risk is that you may get a study drug that does not help treat your disease or that makes your condition or disease worse. Another risk is that there may be side effects. All cancer treatments can have side effects, which can range from mild and reversible to severe, long lasting and possibly life-threatening. There is a great deal of variability among side effects of different cancer treatments and between individuals. In a research study, all of the risks or side effects may not be known before you start the study. You need to tell your doctor or a member of the study team immediately if you experience any side effects. Everyone in the research study will be watched carefully for side effects. You will be monitored during the administration of study drugs. If you experience side effects, they may go away after you stop taking the study drug. Some side effects can be mild; but others can be long lasting and may never go away. Some may be life-threatening or fatal. Since the effect of the study drug(s) taken with other medications may not be known, it is important that you tell the research doctor about all prescription and non-prescription drugs, herbal preparations and nutritional supplements that you are taking or planning to take. There may also be some foods that you should avoid while on this research study and your research doctor will review this information with you. During the research study, you will be notified of newly discovered side effects or significant findings, which may affect your health or willingness to participate. You may be asked to sign a new consent form that shows that you have been informed of new information relating to this research study.

Flexible sigmoidoscopy is generally a safe test although rare complications can occur. These can include some mild pain or discomfort, like a feeling of fullness, felt during this test. Even more rarely (less than 1 in 10,000 times), a hole (perforation) can be made in the side of the rectum or colon that can require surgical intervention.

Biopsies are normally performed under the guidance of an imaging technique. Each procedure requires a separate consent prior to the biopsy. Biopsies of the colon are performed by inserting biopsy forceps through the endoscope and removing a small piece of tissue. Minor bleeding or pain, the most common complications resulting from endoscopic biopsy, complicate less than 1 of every 3000 (0.03%) colonoscopic procedures. This study requires 24 biopsies per procedure. A study of the safety of research biopsies by the National Institutes of Health has determined that more than 20 biopsies per procedure, including as many as 85, is well tolerated and appears to have no more than minimal risk without increasing the risk of otherwise routine colonoscopy. The risks may include:
Pain and discomfort. The amount of pain and discomfort will vary, depending on the location of the biopsy site. These risks can be discussed with the study doctor.  
Minor bleeding at the biopsy site. Major bleeding episodes that require blood transfusions or hospitalization are extremely rare.  
Page 10 of 24 DFCI Protocol Number: 19-402 Approved Date (DFCI IRB Approval): 12/28/2021 Date Posted for Use: 12/29/2021  
  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 Tenderness at the biopsy site. Scarring at the biopsy site. Rarely, an infection at the biopsy site.  
Uncommonly, complications from biopsies can be life threatening. As with any interventional procedure, other potentially serious complications from bleeding or organ damage may occur. These might require additional surgical intervention.

You will have 2 blood draws during the study. A small amount of blood (12 mLs or approximately 2.5 teaspoons) will be taken at each blood draw and poses minimal risk. The total blood collected during the study will be 24 mLs. The risk of blood draws include:
Discomfort at the site of blood draw.  
Bruising, bleeding, infection.  
Rarely fainting.

The drugs used in this research study may affect a fetus. While participating in this research study, you should not:
become pregnant nurse a baby father a baby We can provide counseling about preventing pregnancy for either male or female study participants. Let your doctor know immediately if you become pregnant or find out that you are going to be the father of a child. If your partner becomes pregnant while you are on the study, it may be critical to share information regarding your participation in this research study with that person. Your research doctor should also be told if this happens.

Page 11 of 24 DFCI Protocol Number: 19-402 Approved Date (DFCI IRB Approval): 12/28/2021 Date Posted for Use: 12/29/2021  
  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 Generally, hospitals will keep some of your tissue. There is a small risk that when this tissue is collected and the sample is submitted to the biobank, your tissue could be used up and unavailable for use in the future.

Because of side effects or the time required for tests and clinic visits while you are on this research study, you may be unable to keep up with your normal daily activities. The questionnaires used in this study may be upsetting. If you find the questionnaires upsetting, you may speak with the research doctor or ask to be referred for additional emotional support.

Taking part in this research study may or may not benefit you. We hope the information learned from this research study will provide more information about the effect of daily 4-gram AMR101 treatment on fatty acid composition in colorectal tissue, on the gut microbiome and metabolome, and gene expression profile of colorectal tissue among individuals with a history of colorectal adenoma.

If you think you have been injured as a result of taking part in this research study, tell the person in charge of this research study as soon as possible. The research doctor's name and phone number are listed in this consent form.  
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 BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 The treating hospital will offer you the care needed to treat injuries directly resulting from taking part in this research. These treatments may be billed to you or your insurance company. You will be responsible for deductibles, co-payments and co-insurance. There are no plans to pay you or give you other compensation for the injury. You do not give up your legal rights by signing this form. We will need to collect certain personal information about you for insurance or payment reporting purposes, such as your name, date of birth, gender, social security number or Medicare identification number and information related to this research study. We may be required to report this information to the Centers for Medicare & Medicaid Services. We will not use this information for any other purpose. If you go to the Emergency Room or to another hospital or doctor it is important that you tell them that you are in this research. If possible, you should give them a copy of this consent form.
Clinical trial: NCT04216251
Section: Procedures
Subsections: Before The Research Starts (Screening):|Study Treatment Overview:|Study Visit: Initial (Baseline) Visit|This Visit Will Involve The Following:|Study Visit 2: Final Visit, Study Treatment Ends|Collection And Processing Of Biospecimens:

After signing this consent form, you will be asked to undergo some screening tests or procedures to find out if you can be in the research study. Many of these tests and procedures are likely to be part of regular care and may be done even if it turns out that you do not take part in the research study. If you have had Page 5 of 24  
  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 some of these tests or procedures recently, they may or may not have to be repeated.  
**A medical history,** which includes questions about your health, current medications, and any allergies.  
**Performance status**, which evaluates how you are able to carry on with your usual activities.  
If these tests show that you are eligible to participate in the research study, you may begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

**Oral Study Drug(s):** Each study treatment cycle lasts 8 weeks during which time you will be taking the study drug 2 times per day unless dose reduction is indicated. This will continue for up to 12 weeks.  
If you take part in this research study, you will be given a drug diary. You will be asked to document information in the drug diary about the study treatment you are being asked to take.

At the baseline visit, your physician will obtain written, informed consent for the study as well as a standard clinical consent to perform a flexible sigmoidoscopy. This flexible sigmoidoscopy is similar to your previous colonoscopy. During the procedure the endoscope is only inserted a few inches past your rectum. This flexible sigmoidoscopy will be performed without a bowel preparation, which means that you do not have to drink any laxative preparation in advance of the procedure. At this visit, you will undergo measurements of height, weight, waist and hip circumference and provide blood and urine specimens. A study gastroenterologist will then perform the flexible sigmoidoscopy, advancing only about 6-10 inches. Thus, you will not require any sedation for this procedure. No more than a total of 24 mucosal biopsies will be taken from the rectum and sigmoid colon and immediately placed in collection tubes.

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**Clinical Exams**: During this visit you will have a physical exam and you  
  
will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.  
**A lifestyle questionnaire and a nutritional survey.** Our research assistant will help you complete a questionnaire and a nutritional survey which evaluate your lifestyle risk factors, current nutritional intake, and dietary trends.  
**Blood samples drawn.** Approximately 2.5 teaspoons of blood (12 mLs)
**Flexible sigmoidoscopy,** where **up to 24 normal colon tissue biopsies**
will be collected.  
**Urine sample provided.** **Stool specimen collected** (during flexible sigmoidoscopy)
**Confirm or schedule final visit,** which will occur at least 8 weeks but no more than 12 weeks following this initial visit.

This visit will involve the following:
**Return drug bottle with any remaining pills.**
**Clinical exams**: During this visit you will have a brief physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.  
**A second lifestyle questionnaire and a nutritional survey**
**Blood samples drawn.** Approximately 2.5 teaspoons of blood (12 mLs)
**Urine sample provided.**
**Flexible sigmoidoscopy,** where **up to 24 normal colon tissue biopsies**
will be collected.  
**Stool specimen collected** (during flexible sigmoidoscopy)

Immediately following each flexible sigmoidoscopy, urine specimens will be aliquoted and blood specimens will be centrifuged into plasma and buffy coat. Stool specimens will be stored in a cryovial and immediately frozen. Colon Page 8 of 24  
  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 biopsies will be immediately frozen for future RNA-seq analysis. Yield from these procedures typically exceeds requirements for RNA-seq. Thus, any excess colon tissue will be banked for future studies. All aliquots of stool, urine, plasma, buffy coat, and tissue will be frozen at -80°C until analysis which will be conducted by a third party.
Clinical trial: NCT04216251
Section: Purpose of Research
Subsections: 1. Why Am I Being Invited To Take Part In A Research Study?|A. Why Is This Research Study Being Done?

You are invited to take part in this research study, because you have previously undergone a colonoscopy at Massachusetts General Hospital and had an adenoma removed during this previous procedure.

This research study is a chemoprevention clinical trial, designed tests the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved AMR101 as a treatment for any disease. In this research study, we are investigating the use of AMR101 as a potential chemopreventive agent to reduce risk of colorectal cancer. 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 our human body and has to be obtained through diet or supplemented to maintain normal function of our body. Marine omega-3 fatty acid is well known to reduce inflammation. Substantial evidence has demonstrated that people with higher intake of marine omega-3 fatty acid have a lower likelihood of developing colon cancer. However, there remains uncertainty surrounding this mode of action. By performing this research study, we hope to investigate the mode of action of marine omega-3 fatty acid on the gut bacteria and the immune system, which may lead to the use of marine omega-3 fatty acid as an effective agent to prevent colon cancer.
Clinical trial: NCT04216251
Section: Voluntary Participation
Subsections: R. Documentation Of Consent

My signature below indicates:
I have had enough time to read the consent and think about participating in this study; I have had all of my questions answered to my satisfaction; I am willing to participate in this study; I have been told that my participation is voluntary, and I can withdraw at any time Signature of Participant Date or Legally Authorized Representative Relationship of Legally Authorized Representative to Participant Page 22 of 24 DFCI Protocol Number: 19-402 Approved Date (DFCI IRB Approval): 12/28/2021  
  
Date Posted for Use: 12/29/2021  
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 To be completed by person obtaining consent:
Clinical trial: NCT04216251
Section: Withdrawal from Study
Subsections: D. What Will Happen If I Am Removed From The Study Or Decide To End My Participation In The Research?

You may be taken off the research study for any reason including:
It is considered to be in your best interest The study treatment or procedures are found to be unsafe or ineffective There is any problem with following study treatments and procedures You are a female and become pregnant or plan to become pregnant Your condition worsens A decision is made to end the study Or for other unforeseen reasons that make it necessary to stop your participation in the research study
You can also choose to stop participating in the research study at any time. Tell the research doctor if you are thinking about stopping or decide to stop. He or she will tell you how to stop. Leaving the research study will not affect your medical care outside of the research study. It is important to tell the research doctor if you are thinking about stopping so your research doctor can evaluate the risks from stopping the drug.  
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BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates OHRS Version: 1.31.2020 It is important to note that although you may withdraw from study participation, the FDA requires that any information collected up to the point of your withdrawal cannot be removed from study records. Additionally, the research doctor may consult public records after you have withdrawn from the study. If you decide to withdraw from a study that involves de-identified samples, it will not be possible to remove the samples and data that have already been submitted to a database or biobank.