- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03428477
EPA for Metastasis Trial 2 (EMT2)
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Mark Hull
- Phone Number: 0113 343 8650
- Email: m.a.hull@leeds.ac.uk
Study Locations
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-
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Aintree, United Kingdom
- Aintree University Hospitals NHS Foundation Trust
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Birmingham, United Kingdom
- University Hospitals Birmingham NHS Foundation Trust
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Cambridge, United Kingdom
- Cambridge UniversityHospitals NHS Foundation Trust
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Cardiff, United Kingdom
- University Hospital of Wales
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Leeds, United Kingdom
- Leeds Teaching Hospitals NHS Foundation Trust
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London, United Kingdom
- Royal Free London NHS Foundation Trust
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London, United Kingdom
- King's College London
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Newcastle, United Kingdom
- Newcastle Upon Tyne Hospitals NHS Foundation Trust
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Nottingham, United Kingdom
- Nottingham University Hospitals NHS Trust
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Sheffield, United Kingdom
- Sheffield Teaching Hospitals NHS Foundation Trust
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Southampton, United Kingdom
- University Hospital Southampton NHS Foundation Trust
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Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 9DU
- Oxford University Hospital NHS Foundation Trust
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Royal Hampshire
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Basingstoke, Royal Hampshire, United Kingdom, RG24 9NA
- Hampshire Hospitals NHS Foundation Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Icosapent Ethyl (EPA-EE)
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.
|
Composition: soft amber to light yellow, oblong gelatin capsules.
One capsule contains 1g pure EPA-EE Dose: 4 capsules per day
Other Names:
|
Placebo Comparator: Placebo
Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening).
|
Composition: soft, amber to light yellow, oblong gelatin capsules containing light mineral oil: Dose: 4 capsules per day |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Minimum of 2 years follow-up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: Minimum of 2 years follow-up
|
The time from randomisation to death, from any cause (key secondary endpoint)
|
Minimum of 2 years follow-up
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Safety and Tolerability of Icosapent Ethyl
Time Frame: Minimum of 2 years follow-up
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The number of participants with treatment-emergent adverse events as defined by CTCAE v4.0
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Minimum of 2 years follow-up
|
Patient reported quality of life 1
Time Frame: Minimum of 2 years follow-up
|
Measured using the EQ-5D questionnaire
|
Minimum of 2 years follow-up
|
Patient reported quality of life 2
Time Frame: Minimum of 2 years follow-up
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Measured using the EORTC QLQ-C30 questionnaire
|
Minimum of 2 years follow-up
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Patient reported quality of life 3
Time Frame: Minimum of 2 years follow-up
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Measured using the QLQ-LMC21 questionnaire
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Minimum of 2 years follow-up
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New Primary Cancers
Time Frame: Minimum of 2 years follow-up
|
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)
|
Minimum of 2 years follow-up
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Red Blood Cell Membrane EPA content (exploratory endpoint)
Time Frame: Samples taken at baseline, surgery and 6 months after surgery
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EPA content measured at baseline, surgery and 6 months after surgery.
Samples taken at selected sites only
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Samples taken at baseline, surgery and 6 months after surgery
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Change in lean body mass (exploratory endpoint)
Time Frame: 6 months and up to 4 years follow up
|
Change in lean body mass measured by CT scanning during follow-up as assessed by the L3 skeletal muscle index score.
Scans reviewed from selected sites only
|
6 months and up to 4 years follow up
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mark Hull, University of Leeds
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Liver Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Neoplastic Processes
- Colorectal Neoplasms
- Neoplasm Metastasis
- Liver Neoplasms
- Colonic Neoplasms
- Platelet Aggregation Inhibitors
- Lipid Regulating Agents
- Eicosapentaenoic acid ethyl ester
Other Study ID Numbers
- MO16/053
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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).
IPD Sharing Time Frame
IPD Sharing Access Criteria
Data will be released for secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (scientific rigour and information governance and security), and that suitable resources are available. Data will be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject. No IPD will be released before an appropriate agreement is in place governing data retention, usually stipulating that data recipients must delete their copy of the data at the end of the project.
The CTRU believes it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, key trial documents and any other information required to reuse the datasets.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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