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OMega-3 Fatty Acid for the Immune Modulation of Colorectal Cancer (OMICC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03661047
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : May 12, 2020
Sponsor:
Collaborator:
Harvard School of Public Health
Information provided by (Responsible Party):
Mingyang Song, Massachusetts General Hospital

Brief Summary:
This is a prospective, double-blind, placebo-controlled, randomized clinical trial to assess the effects of daily 4-gram marine omega-3 polyunsaturated fatty acid (MO3PUFA), through treatment with AMR101 (VASCEPA, icosapent ethyl) on the tumor immune microenvironment and gut microbiome in patients who are diagnosed with colorectal cancer or with a colorectal mass or polyp suspected to be a cancer or advanced adenoma and will undergo surgical resection or interventional endoscopy at the Massachusetts General Hospital (MGH). It uses the novel "window-of-opportunity" clinical trial design to take advantage of the window of time between cancer/mass/polyp diagnosis and surgery to examine the effect of therapeutic agents on tumor pathologic and molecular features unperturbed by prior therapies.

Condition or disease Intervention/treatment Phase
Colon Cancer Drug: AMR101 (VASCEPA, icosapent ethyl) Phase 2

Detailed Description:

This research study is evaluating the effect of AMR101, as a chemopreventive agent to reduce risk of colorectal cancer in individuals with a history of colorectal cancer, colorectal mass or polyp(s).

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 during which participants will complete a lifestyle questionnaire and a nutritional survey. A drug diary will be provided to be completed. Measurements will be taken, and blood and stool specimens will be collected. Tumor, colorectal mass, or polyp tissue will be collected for research purposes at the time of surgery or interventional endoscopy.

AMR101 administered daily, orally for up to 30 days and it is expected that 36 participants will take part in this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled, stratified, randomized clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: OMICC: OMega-3 Fatty Acid for the Immune Modulation of Colorectal Cancer
Actual Study Start Date : November 30, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Omega-3 treatment
Daily 4-gram marine omega-3 polyunsaturated fatty acid (MO3PUFA), through treatment with AMR101 (VASCEPA, icosapent ethyl)
Drug: AMR101 (VASCEPA, icosapent ethyl)
Oral administration, 4 grams per day
Other Name: Omega-3 fatty acid

Placebo Comparator: Placebo
Identical placebo
Drug: AMR101 (VASCEPA, icosapent ethyl)
Oral administration, 4 grams per day
Other Name: Omega-3 fatty acid




Primary Outcome Measures :
  1. The change in the marine omega-3 polyunsaturated fatty acid (MO3PUFA) composition in colorectal tissues as a result of the AMR101 treatment for up to 30 days. [ Time Frame: An average of 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 :
  1. The change in Tumor CD8+ T cells in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The influence of MO3PUFA treatment on the balance of Teff and Treg cells will be measured by the ratio of CD8+/Treg in the tumor microenvironment.

  2. The change in gene expression profile of colorectal tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 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.

  3. The change in protein levels of FOXP3 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell inhibitory markers will be measured before and after intervention.

  4. The change in protein levels of IL10 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell inhibitory markers will be measured before and after intervention.

  5. The change in protein levels of LAG-3 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell inhibitory markers will be measured before and after intervention.

  6. The change in protein levels of CD49b in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell inhibitory markers will be measured before and after intervention.

  7. The change in protein levels of CTLA-4 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell immune checkpoints will be measured before and after intervention.

  8. The change in protein levels of TIGIT in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell immune checkpoints will be measured before and after intervention.

  9. The change in protein levels of TIM-3 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell immune checkpoints will be measured before and after intervention.

  10. The change in protein levels of PD-1 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell immune checkpoints will be measured before and after intervention.

  11. The change in protein levels of PD-L1 in the tumor tissue between pre- and post- AMR101 treatment period. [ Time Frame: An average of 2 years after study completion ]
    The changes in protein levels of T cell immune checkpoints will be measured before and after intervention.

  12. The change in the gut microbiome composition and function between pre- and post- AMR101 treatment period [ Time Frame: An average of 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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

Participants have histologically confirmed adenocarcinoma of the colon that is localized, with no evidence of distant metastasis (stage I, II, or III), and for which surgical resection of the primary tumor is being planned;

OR

Participants may have a colon biopsy that is suspicious for adenocarcinoma if clinical and/or endoscopic findings strongly support the presence of malignancy, and if surgical resection is being planned. NOTE: In the unlikely event that the final pathology of the surgical resection specimen is consistent with high-grade adenoma or dysplasia, the patient will not be considered ineligible and collected research samples will still be utilized.

OR

Participants have a diagnosis of a colorectal mass or polyp suspected to be a cancer or advanced adenoma at the most recent colonoscopy and are being referred to an advanced endoscopist to undergo interventional endoscopy within 30 days.

Age >= 18 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.

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

Patients must be sufficiently healthy to undergo surgery/interventional endoscopy.

The effects of AMR101 on the developing human fetus 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 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.

Prior systemic or radiotherapy treatment for colorectal cancer.

Participants who are receiving any other investigational agents.

Concurrent use of other anti-cancer therapy, including chemotherapy agents, targeted agents, biological agents, immunotherapy, or investigational agents not otherwise specified in this protocol.

Inability or unwillingness to swallow pills.

History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease that could interfere with absorption of oral medications.

History of allergic reactions attributed to fish or compounds of similar chemical or biologic composition to MO3PUFA.

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.

Known bleeding tendency/condition (e.g. von Willebrand disease)

Current use of anticoagulants or antiplatelet therapies, including aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs, including Ibuprofen [Advil, Motrin], Naproxen [Aleve, Anaprox DS, Naprosyn], and Celecoxib [Celebrex]), Heparin, Warfarin, Dalteparin sodium, Bivalirudin, Argatroban, Lepirudin, Heparin Sodium, Heparin/Dextrose, and an unwillingness or inability to discontinue anticoagulants.

Any 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, in the opinion of the investigator, may increase the risks associated with study participation or study treatment, limit compliance with study requirements, or interfere with the interpretation of study results.

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.

Presence of synchronous (at the same time) malignancy for which the patient is currently receiving active treatment.

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.

Inclusion of Women and Minorities

Women and minorities will be eligible for this study without alteration in eligibility criteria. Enrollment of these underrepresented populations to this trial will be encouraged.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03661047


Contacts
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Contact: Mingyang Song, MD, ScD 6176434464 mis911@mail.harvard.edu
Contact: Marina Magicheva-Gupta, MPH mmagicheva-gupta@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Mingyang Song, MD, ScD    617-643-4464    mis911@mail.harvard.edu   
Sponsors and Collaborators
Mingyang Song
Harvard School of Public Health
Investigators
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Principal Investigator: Mingyang Song, MD, ScD Massachusetts General Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mingyang Song, Prinicipal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03661047    
Obsolete Identifiers: NCT03419455
Other Study ID Numbers: 18-097
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: May 12, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mingyang Song, Massachusetts General Hospital:
Nutrition
Omega-3 fatty acid
Fish oil
Tumor microenvironment
Immune response
Gut microbiota
Polyp
Colorectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Intestinal Diseases
Digestive System Diseases
Gastrointestinal Diseases
Rectal Diseases
Eicosapentaenoic acid ethyl ester
Platelet Aggregation Inhibitors