Prebiotic Effect of Eicosapentaenoic Acid Treatment for Colorectal Cancer Liver Metastases
NCT ID: NCT04682665
Last Updated: 2024-12-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
81 participants
OBSERVATIONAL
2021-09-16
2024-07-31
Brief Summary
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Detailed Description
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There are observational and laboratory data supporting the notion that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has anti-CRC activity. These include a phase 2 'window of opportunity' randomised, placebo-controlled trial of EPA provided before surgery for resection of CRC liver metastasis (called the EMT study). A signal that EPA improved progression-free and overall survival after liver surgery provided the rationale for the EMT2 trial, which is a randomised, double-blind placebo-controlled phase 3 trial of the effect of EPA (started before surgery but continued post-operatively) on CRC recurrence and survival after surgery for resectable liver metastases \[ClinicalTrials.gov NCT03428477 and EudraCT Number: 2016-000628-24\].
The mechanism(s) by which EPA might influence post-operative survival are not well understood. Recent data support the idea that the anti-CRC benefit of EPA may be mediated by modulating the intestinal microbiota and ameliorating tumour-permissive immunosuppressive mechanisms, including inhibition of the activity of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as reduced synthesis of inflammatory mediators such as prostaglandin (PG) E2 and chemokine (C-C motif) ligand 2 (CCL2). Mice fed with a high-EPA-containing diet demonstrate 1) increased abundance of gut bacteria, such as Bifidobacterium and Lactobacillus genera that support the host anti-tumour immune response and improve the efficacy of cancer immunotherapy, and 2) decreased abundance of lipopolysaccharide (LPS)-producing bacteria that trigger chronic inflammation and can promote CRC. These data support a hypothesis that a prebiotic effect of EPA abrogates intra-tumoural immunosuppression and ameliorates systemic inflammation to improve survival of CRCLM patients.
EMT2 trial participants are ideally placed to provide biospecimens that can be analysed in order to understand the mechanism(s) of action of EPA given that the laboratory data can eventually be linked to the clinical outcomes from the trial. Biospecimens can be obtained without interference with the EMT2 trial protocol. Stool, urine, and blood samples will be obtained 1) after EMT2 trial randomization, before starting EPA or placebo, 2) just before surgery, and 3) at 6-monthly intervals thereafter, plus liver metastases tumour tissue during surgery. Using these biospecimens, the microbiome and immune pathways altered by EPA will be investigated in relation to participant survival. Mechanistic insights about the anti-CRC activity of EPA from the biospecimen collection project will maximize the knowledge and insights gained from the EMT2 trial and its participants, thereby leading to personalized use of EPA, which will be targeted at those most likely to benefit.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Experimental
Patients randomized to the experimental arm of the EMT2 trial, receiving Icosapent Ethyl (EPA-EE) according to the EMT2 protocol.
Icosapent Ethyl Oral Capsule
Soft gelatin capsules containing 1g pure EPA-EE. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening.
Placebo comparator
Patients randomized to the placebo comparator arm of the EMT2 trial, receiving placebo capsules according to the EMT2 protocol.
Placebo
Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening).
Interventions
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Icosapent Ethyl Oral Capsule
Soft gelatin capsules containing 1g pure EPA-EE. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening.
Placebo
Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening).
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Massachusetts General Hospital
OTHER
Massachusetts Institute of Technology
OTHER
Harvard School of Public Health (HSPH)
OTHER
University of Bradford
OTHER
University of Leeds
OTHER
Responsible Party
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Mark A Hull, PhD FRCP
Professor of Gastroenterology
Principal Investigators
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Mark Hull
Role: PRINCIPAL_INVESTIGATOR
University of Leeds
Locations
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St James's University Hospital
Leeds, , United Kingdom
University of Liverpool
Liverpool, , United Kingdom
Countries
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Other Identifiers
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20/YH/0306
Identifier Type: -
Identifier Source: org_study_id