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

NCT03661047 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 18-097
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer

Keywords

Nutrition; Omega-3 fatty acid; Fish oil; Tumor microenvironment; Immune response; Gut microbiota; Polyp; Colorectal cancer

Outcome Measures

Primary Outcomes (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.

  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.

  An average of 2 years after study completion

Secondary Outcomes (12)

• The change in Tumor CD8+ T cells in the tumor tissue between pre- and post- AMR101 treatment period.

  An average of 2 years after study completion

• The change in gene expression profile of colorectal tissue between pre- and post- AMR101 treatment period.

  An average of 2 years after study completion

• The change in protein levels of FOXP3 in the tumor tissue between pre- and post- AMR101 treatment period.

  An average of 2 years after study completion

• The change in protein levels of IL10 in the tumor tissue between pre- and post- AMR101 treatment period.

  An average of 2 years after study completion

• The change in protein levels of LAG-3 in the tumor tissue between pre- and post- AMR101 treatment period.

  An average of 2 years after study completion

Study Arms (2)

Omega-3 treatment

ACTIVE COMPARATOR

Daily 4-gram marine omega-3 polyunsaturated fatty acid (MO3PUFA), through treatment with AMR101 (VASCEPA, icosapent ethyl)

Drug: AMR101 (VASCEPA, icosapent ethyl)

Placebo

PLACEBO COMPARATOR

Identical placebo

Drug: AMR101 (VASCEPA, icosapent ethyl)

Interventions

AMR101 (VASCEPA, icosapent ethyl) DRUG

Oral administration, 4 grams per day

Also known as: Omega-3 fatty acid

Omega-3 treatment; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Harvard School of Public Health (HSPH): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Hang D, Kvaerner AS, Ma W, Hu Y, Tabung FK, Nan H, Hu Z, Shen H, Mucci LA, Chan AT, Giovannucci EL, Song M. Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals. Am J Clin Nutr. 2019 Mar 1;109(3):635-647. doi: 10.1093/ajcn/nqy295.

  PMID: 30834441 DERIVED

• Kvaerner AS, Hang D, Giovannucci EL, Willett WC, Chan AT, Song M. Trajectories of body fatness from age 5 to 60 y and plasma biomarker concentrations of the insulin-insulin-like growth factor system. Am J Clin Nutr. 2018 Aug 1;108(2):388-397. doi: 10.1093/ajcn/nqy103.

  PMID: 30101328 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Polyps; Colorectal Neoplasms

Interventions

eicosapentaenoic acid ethyl ester; Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Rectal Diseases

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• Andrew T. Chan, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Model Details: Double-blind, placebo-controlled, stratified, randomized clinical trial

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 7, 2018
• Study Start: November 30, 2019
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: November 17, 2021

Record last verified: 2021-11

Locations

US (1)