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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
Hull, M.A. Ow, P.L. Ruddock, S. Brend, T. Smith, A.F. Marshall, H. Song, M. Chan, A.T. Garrett, W.S. Yilmaz, O.
Hull, M.A.
Ow, P.L.
Ruddock, S.
Brend, T.
Smith, A.F.
Marshall, H.
Song, M.
Chan, A.T.
Garrett, W.S.
Yilmaz, O.
Publication Date
2023-11
End of Embargo
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Rights
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2023-10-26
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Department
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Additional title
Abstract
There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal
cancer (CRC). The omega-3 polyunsaturated fatty acid
eicosapentaenoic acid (EPA) is safe, well-tolerated and
has anti-inflammatory as well as antineoplastic properties.
A phase 2 randomised trial of preoperative EPA free fatty
acid 2 g daily in patients undergoing surgery for CRC liver
metastasis showed no difference in the primary endpoint
(histological tumour proliferation index) compared with
placebo. However, the trial demonstrated possible benefit
for the prespecified exploratory endpoint of postoperative
disease-free survival. Therefore, we tested the hypothesis
that EPA treatment, started before liver resection surgery
(and continued postoperatively), improves CRC outcomes
in patients with CRC liver metastasis.
Methods and analysis: The EPA for Metastasis Trial 2 trial
is a randomised, double-blind, placebo-controlled, phase 3
trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa))
daily in patients undergoing liver resection surgery for
CRC liver metastasis with curative intent. Trial treatment
continues for a minimum of 2 years and maximum of
4 years, with 6monthly assessments, including quality
of life outcomes, as well as annual clinical record review
after the trial intervention. The primary endpoint is CRC
progression-free survival. Key secondary endpoints are
overall survival, as well as the safety and tolerability of IPE.
A minimum 388 participants are estimated to provide 247
CRC progression events during minimum 2-year follow-up,
allowing detection of an HR of 0.7 in favour of IPE, with a
power of 80% at the 5% (two sided) level of significance,
assuming drop-out of 15%.
Ethics and dissemination: Ethical and health research
authority approval was obtained in January 2018. All data
will be collected by 2025. Full trial results will be published
in 2026. Secondary analyses of health economic data,
biomarker studies and other translational work will be
published subsequently.
Trial registration number NCT03428477.
Version
Published version
Citation
Hull MA, Ow PL, Ruddock S et al (2023) 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. 13(11): e077427.
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Article