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.

Autor:	Hull MA; Leeds Institute of Medical Research, University of Leeds, Leeds, UK m.a.hull@leeds.ac.uk., Ow PL; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Ruddock S; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Brend T; Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Smith AF; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Marshall H; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Song M; Harvard TH Chan School of Public Health, Boston, Massachusetts, USA., Chan AT; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA., Garrett WS; Harvard TH Chan School of Public Health, Boston, Massachusetts, USA., Yilmaz O; Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Boston, Massachusetts, USA., Drew DA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA., Collinson F; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Cockbain AJ; Leeds Teaching Hospitals NHS Trust, Leeds, UK., Jones R; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK., Loadman PM; Institute of Cancer Therapeutics, University of Bradford, Bradford, UK., Hall PS; Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK., Moriarty C; Leeds Teaching Hospitals NHS Trust, Leeds, UK., Cairns DA; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK., Toogood GJ; Leeds Institute of Medical Research, University of Leeds, Leeds, UK.; Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2023 Nov 29; Vol. 13 (11), pp. e077427. Date of Electronic Publication: 2023 Nov 29.
DOI:	10.1136/bmjopen-2023-077427
Abstrakt:	Introduction: 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 6 monthly 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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu