Liver MetastasisPhase 3EMT2NCT03428477
EPA for Metastasis Trial 2
A Phase 3 study testing Icosapent Ethyl in people with Liver Metastasis and Colon Cancer, run by Mark A Hull, PhD FRCP at 13 sites in United Kingdom.
Trial summary
A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastasis, Colon Cancer
- What is being tested?
- Icosapent Ethyl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 418 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- 2 May 2018to 30 Apr 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 years
- Able to provide written informed consent
- Histological diagnosis of colorectal cancer with evidence of liver metastases
- Planned liver resection surgery for colorectal cancer liver metastases with curative intent, including repeat 're-do' colorectal cancer liver metastases surgery (a second independent resection for a separate colorectal cancer liver recurrence)
- Intention to receive IMP prior to colorectal cancer liver metastases surgery
Who cannot join
- Previous CRCLM surgery for the management of the current metastatic disease
- Incurable extra-hepatic metastases
- Current (in the last 2 months) or planned regular (>3 doses per week) use of O3FA-containing drugs or supplements, including Vazkepa®, Omacor®, fish oil and cod-liver oil supplements
- Fish/seafood allergy
- Diagnosis of hereditary fructose intolerance
- Soya or peanut allergy
Show all 17Show fewer
- Inability to comply with trial treatment and follow-up schedule
- Known bleeding tendency/condition (e.g. von Willebrand disease)
- A previous malignancy within the last 5 years other than:
- colorectal cancer
- non-melanoma skin cancer where treatment consisted of resection only or radiotherapy
- ductal carcinoma in situ (DCIS) where treatment consisted of resection only
- cervical carcinoma in situ where treatment consisted of resection only
- superficial bladder carcinoma where treatment consisted of resection only
- A previous malignancy where the patient has been disease free for ≤ 5 years
- Pregnant or breastfeeding women or women of childbearing potential not willing to use effective contraceptive measures. Women of childbearing potential are defined as fertile, following menarche and until becoming post-menopausal, unless permanently sterile
- Men defined as fertile (post-pubescent and not permanently sterile by vasectomy or bilateral orchidectomy) and not willing to use effective contraceptive measures if appropriate.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United Kingdom13 sites
Aintree University Hospitals NHS Foundation Trust
Aintree
Hampshire Hospitals NHS Foundation Trust
Basingstoke, Royal Hampshire, RG24 9NA
University Hospitals Birmingham NHS Foundation Trust
Birmingham
Cambridge UniversityHospitals NHS Foundation Trust
Cambridge
University Hospital of Wales
Cardiff
Leeds Teaching Hospitals NHS Foundation Trust
Leeds
King's College London
London
Royal Free London NHS Foundation Trust
London
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle
Nottingham University Hospitals NHS Trust
Nottingham
Oxford University Hospital NHS Foundation Trust
Oxford, Oxfordshire, OX3 9DU
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield
University Hospital Southampton NHS Foundation Trust
Southampton
About this study
Official title: A Randomised Placebo-controlled Phase III Trial of the Effect of the Omega-3 Fatty Acid Eicosapentaenoic Acid (EPA) on Colorectal Cancer Recurrence and Survival After Surgery for Resectable Liver Metastases
A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. A previous small study (the EMT study) suggested a possible survival benefit in patients who took the naturally-occurring omega-3 fatty acid EPA (a fish oil supplement) before liver surgery. The EMT2 study is a larger study which will recruit 448 men and women with liver metastases from bowel cancer. Trial participants will receive either Icosapent Ethyl (pure EPA derived from fish oil) or placebo (dummy capsules). EMT2 will investigate whether patients who take this supplement before liver surgery and for up to four years after surgery, remain free of recurrence for longer than those who take placebo (dummy capsules)
Read the detailed description
Despite significant advances in diagnosis and treatment of colorectal cancer (CRC), it remains the second most common cause of cancer-related death in the UK. The majority of deaths from CRC are related to distant metastasis, predominantly to the liver. Overall 5-year survival following liver resection and adjuvant chemotherapy for colorectal cancer liver metastases (CRCLM) is, at best, 40-60%. Despite surgery with curative intent, up to 60% of patients develop recurrence within 2 years of surgery. The preliminary EMT study was a Phase II RCT of EPA 2 g daily in patients (n=88) undergoing liver resection surgery for CRCLM. Although there was no difference in the primary endpoint (tumour proliferation index), metastases from the EPA arm had a lower vascularity score (suggesting possible anti-angiogenic activity) than placebo-treated tumours. Although EPA (or placebo) treatment was limited to the pre-operative period, overall survival (OS) and disease-free survival (DFS) were specified as exploratory end-points on the basis that oral dosing with EPA before liver surgery would provide tissue EPA exposure in the immediate peri-operative period with prolonged bioavailability in the post-operative period due to the slow tissue 'washout' kinetics of EPA. Survival analysis demonstrated that the median DFS in the EPA group was 22.6 months compared with 14.7 months in the placebo group. Any DFS benefit was explained by a reduction in CRC recurrence from 12 months after surgery onwards.
The EMT2 study is a randomised, double-blind, placebo-controlled, multi-centre, phase III trial of the omega-3 fatty acid (O3FA) eicosapentaenoic acid (EPA) as the ethyl ester (icosapent ethyl [IPE; Vascepa®]) in patients undergoing liver resection surgery for colorectal cancer liver metastasis (CRCLM) with curative intent designed to determine whether EPA treatment improves Progression-Free Survival (PFS). A key secondary objective is overall survival (OS).
Investigators will recruit adult individuals listed for CRCLM resection with curative intent.
Randomisation will be 1:1 to receive either IPE capsules or placebo capsules. 4 capsules per day containing IPE (equivalent to 4 g EPA-ethyl ester [EE] daily) or 4 placebo capsules per day. Participants will start treatment a prior to CRCLM surgery and will continue to receive treatment for a minimum of 2 years and a maximum of 4 years post-liver resection. Participants are followed up for 60 days beyond the end of treatment.
Participants are clinically assessed 6 months post-operatively (from liver resection) and at 6-monthly intervals thereafter for disease progression/recurrence.
- Conditions
- Liver Metastasis, Colon Cancer
- Being tested
- Icosapent Ethyl, Placebo
- Keywords
- Liver metastases, Colon Cancer
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Icosapent EthylDrug
Also called Vascepa
Composition: soft amber to light yellow, oblong gelatin capsules. One capsule contains 1g pure EPA-EE Dose: 4 capsules per day
PlaceboOther
Composition: soft, amber to light yellow, oblong gelatin capsules containing light mineral oil:
Dose: 4 capsules per day
| Study group | Role | What they receive |
|---|---|---|
| Icosapent Ethyl (EPA-EE) | Experimental | Soft gelatin capsules containing 1g pure EPA-EE equivalent to 914mg EPA-FFA. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening. Receives: Drug: Icosapent Ethyl |
| Placebo | Placebo comparator | Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from randomisation to death (from any cause), first documented evidence of disease progression, new recurrence or clinical deterioration unequivocally due to disease progression
Measured: Minimum of 2 years follow-up
Secondary outcomes (6)
Overall Survival (OS)
The time from randomisation to death, from any cause (key secondary endpoint)
Measured: Minimum of 2 years follow-up
Safety and Tolerability of Icosapent Ethyl
The number of participants with treatment-emergent adverse events as defined by CTCAE v4.0
Measured: Minimum of 2 years follow-up
Patient reported quality of life 1
Measured using the EQ-5D questionnaire
Measured: Minimum of 2 years follow-up
Patient reported quality of life 2
Measured using the EORTC QLQ-C30 questionnaire
Measured: Minimum of 2 years follow-up
Patient reported quality of life 3
Measured using the QLQ-LMC21 questionnaire
Measured: Minimum of 2 years follow-up
New Primary Cancers
Excluding DCIS, cervical carcinoma in situ, superficial bladder carcinoma where treatment consisted of resection only and non-melanoma skin cancer where treatment consisted of resection or radiotherapy only)
Measured: Minimum of 2 years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2018
- Study start2 May 2018
- Primary completion30 Nov 2025 (estimated)
- Study completion30 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark A Hull, PhD FRCP
- Sponsor type
- University, hospital or other
- Collaborators
- Yorkshire Cancer Research, Amarin Pharma Inc.
- Responsible party
- Sponsor-investigator, Mark A Hull, PhD FRCP, University of Leeds
- Investigators
- Mark Hull, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03428477
- Sponsor's protocol ID
- MO16/053
- Acronym
- EMT2
- Status last verified
- Apr 2025
- First submitted
- 11 Jan 2018
- Last updated
- 18 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets generated during the current study will be available upon request from the Clinical Trials Research Unit at the University of Leeds. De-identified individual participant data datasets generated during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance).
Publications
Hull MA, Ow PL, Ruddock S, Brend T, Smith AF, Marshall H, Song M, Chan AT, Garrett WS, Yilmaz O, Drew DA, Collinson F, Cockbain AJ, Jones R, Loadman PM, Hall PS, Moriarty C, Cairns DA, Toogood GJ. Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol. BMJ Open. 2023 Nov 29;13(11):e077427. doi: 10.1136/bmjopen-2023-077427.
PubMed 38030258
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Placebo-controlled Phase III Trial of the Effect of the Omega-3 Fatty Acid Eicosapentaenoic Acid (EPA) on Colorectal Cancer Recurrence and Survival After Surgery for Resectable Liver Metastases
- ClinicalTrials.gov ID
- NCT03428477
- Acronym / sponsor ID
- EMT2 / MO16/053
- Conditions
- Liver Metastasis, Colon Cancer
- Keywords
- Liver metastases, Colon Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 418 participants (actual)
- Lead sponsor
- Mark A Hull, PhD FRCPUniversity, hospital or other
- Collaborators
- Yorkshire Cancer Research, Amarin Pharma Inc.
- Study start
- 2 May 2018 (actual)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 9 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. A previous small study (the EMT study) suggested a possible survival benefit in patients who took the naturally-occurring omega-3 fatty acid EPA (a fish oil supplement) before liver surgery. The EMT2 study is a larger study which will recruit 448 men and women with liver metastases from bowel cancer. Trial participants will receive either Icosapent Ethyl (pure EPA derived from fish oil) or placebo (dummy capsules). EMT2 will investigate whether patients who take this supplement before liver surgery and for up to four years after surgery, remain free of recurrence for longer than those who take placebo (dummy capsules)
Detailed description
Despite significant advances in diagnosis and treatment of colorectal cancer (CRC), it remains the second most common cause of cancer-related death in the UK. The majority of deaths from CRC are related to distant metastasis, predominantly to the liver. Overall 5-year survival following liver resection and adjuvant chemotherapy for colorectal cancer liver metastases (CRCLM) is, at best, 40-60%. Despite surgery with curative intent, up to 60% of patients develop recurrence within 2 years of surgery. The preliminary EMT study was a Phase II RCT of EPA 2 g daily in patients (n=88) undergoing liver resection surgery for CRCLM. Although there was no difference in the primary endpoint (tumour proliferation index), metastases from the EPA arm had a lower vascularity score (suggesting possible anti-angiogenic activity) than placebo-treated tumours. Although EPA (or placebo) treatment was limited to the pre-operative period, overall survival (OS) and disease-free survival (DFS) were specified as exploratory end-points on the basis that oral dosing with EPA before liver surgery would provide tissue EPA exposure in the immediate peri-operative period with prolonged bioavailability in the post-operative period due to the slow tissue 'washout' kinetics of EPA. Survival analysis demonstrated that the median DFS in the EPA group was 22.6 months compared with 14.7 months in the placebo group. Any DFS benefit was explained by a reduction in CRC recurrence from 12 months after surgery onwards.
The EMT2 study is a randomised, double-blind, placebo-controlled, multi-centre, phase III trial of the omega-3 fatty acid (O3FA) eicosapentaenoic acid (EPA) as the ethyl ester (icosapent ethyl [IPE; Vascepa®]) in patients undergoing liver resection surgery for colorectal cancer liver metastasis (CRCLM) with curative intent designed to determine whether EPA treatment improves Progression-Free Survival (PFS). A key secondary objective is overall survival (OS).
Investigators will recruit adult individuals listed for CRCLM resection with curative intent.
Randomisation will be 1:1 to receive either IPE capsules or placebo capsules. 4 capsules per day containing IPE (equivalent to 4 g EPA-ethyl ester [EE] daily) or 4 placebo capsules per day. Participants will start treatment a prior to CRCLM surgery and will continue to receive treatment for a minimum of 2 years and a maximum of 4 years post-liver resection. Participants are followed up for 60 days beyond the end of treatment.
Participants are clinically assessed 6 months post-operatively (from liver resection) and at 6-monthly intervals thereafter for disease progression/recurrence.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Icosapent Ethyl (EPA-EE) | Experimental | Drug: Icosapent EthylSoft gelatin capsules containing 1g pure EPA-EE equivalent to 914mg EPA-FFA. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening. |
| Placebo | Placebo comparator | Other: PlaceboSoft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged ≥ 18 years
- Able to provide written informed consent
- Histological diagnosis of colorectal cancer with evidence of liver metastases
- Planned liver resection surgery for colorectal cancer liver metastases with curative intent, including repeat 're-do' colorectal cancer liver metastases surgery (a second independent resection for a separate colorectal cancer liver recurrence)
- Intention to receive IMP prior to colorectal cancer liver metastases surgery
Key exclusion criteria (17 listed)
- Previous CRCLM surgery for the management of the current metastatic disease
- Incurable extra-hepatic metastases
- Current (in the last 2 months) or planned regular (>3 doses per week) use of O3FA-containing drugs or supplements, including Vazkepa®, Omacor®, fish oil and cod-liver oil supplements
- Fish/seafood allergy
- Diagnosis of hereditary fructose intolerance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Icosapent EthylAlso: VascepaComposition: soft amber to light yellow, oblong gelatin capsules. One capsule contains 1g pure EPA-EE Dose: 4 capsules per day | Drug | Icosapent Ethyl (EPA-EE) |
| PlaceboComposition: soft, amber to light yellow, oblong gelatin capsules containing light mineral oil: Dose: 4 capsules per day | Other | Placebo |
Primary outcome
Progression Free Survival (PFS)
Time frame: Minimum of 2 years follow-up
PFS is defined as the time from randomisation to death (from any cause), first documented evidence of disease progression, new recurrence or clinical deterioration unequivocally due to disease progression
6 secondary outcomes
Overall Survival (OS)
Time frame: Minimum of 2 years follow-up
Safety and Tolerability of Icosapent Ethyl
Time frame: Minimum of 2 years follow-up
Patient reported quality of life 1
Time frame: Minimum of 2 years follow-up
Patient reported quality of life 2
Time frame: Minimum of 2 years follow-up
Patient reported quality of life 3
Time frame: Minimum of 2 years follow-up
New Primary Cancers
Time frame: Minimum of 2 years follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Derived from this study: PubMed 38030258Hull MA, Ow PL, Ruddock S, Brend T, Smith AF, Marshall H, Song M, Chan AT, Garrett WS, Yilmaz O, Drew DA, Collinson F, Cockbain AJ, Jones R, Loadman PM, Hall PS, Moriarty C, Cairns DA, Toogood GJ. Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol. BMJ Open. 2023 Nov 29;13(11):e077427. doi: 10.1136/bmjopen-2023-077427.
- Individual participant dataSharing planned: Yes. The datasets generated during the current study will be available upon request from the Clinical Trials Research Unit at the University of Leeds. De-identified individual participant data datasets generated during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Hull principal investigator
University of Leeds
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Icosapent Ethyl in people with Liver Metastasis and Colon Cancer, run by Mark A Hull, PhD FRCP at 13 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Minimum of 2 years follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03428477, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2025.