EPA for Metastasis Trial 2 (EMT2)
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|ClinicalTrials.gov Identifier: NCT03428477|
Recruitment Status : Recruiting
First Posted : February 9, 2018
Last Update Posted : May 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Liver Metastasis Colon Cancer||Drug: Icosapent Ethyl Other: Placebo||Phase 3|
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 minimum of 2 weeks 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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||448 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||March 16, 2018|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||January 2023|
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.
Drug: Icosapent Ethyl
Composition: soft amber to light yellow, oblong gelatin capsules. One capsule contains 1g pure EPA-EE Dose: 4 capsules per day
Other Name: Vascepa
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
- 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
- Overall Survival (OS) [ Time Frame: Minimum of 2 years follow-up ]The time from randomisation to death, from any cause (key secondary endpoint)
- Safety and Tolerability of Icosapent Ethyl [ Time Frame: Minimum of 2 years follow-up ]The number of participants with treatment-emergent adverse events as defined by CTCAE v4.0
- Patient reported quality of life 1 [ Time Frame: Minimum of 2 years follow-up ]Measured using the EQ-5D questionnaire
- Patient reported quality of life 2 [ Time Frame: Minimum of 2 years follow-up ]Measured using the EORTC QLQ-C30 questionnaire
- Patient reported quality of life 3 [ Time Frame: Minimum of 2 years follow-up ]Measured using the QLQ-LMC21 questionnaire
- 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)
- Red Blood Cell Membrane EPA content (exploratory endpoint) [ Time Frame: Samples taken at baseline, surgery and 6 months after surgery ]EPA content measured at baseline, surgery and 6 months after surgery. Samples taken at selected sites only
- 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
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): NCT03428477
|Contact: Mark Hull||0113 343 firstname.lastname@example.org|
|Hampshire Hospitals NHS Foundation Trust||Recruiting|
|Basingstoke, Royal Hampshire, United Kingdom, RG24 9NA|
|Contact: Fenella Welsh|
|University Hospital Southampton NHS Foundation Trust||Recruiting|
|Southampton, United Kingdom|
|Contact: Zaed Hamady|
|Principal Investigator:||Mark Hull||University of Leeds|