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

INTERVENTION: Product Name: Icosapent Ethyl Pharmaceutical Form: Capsule, soft INN or Proposed INN: Icosapent Ethyl CAS Number: 73310‐10‐8 Other descriptive name: IPE Concentration unit: g gram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Capsule, soft Route of administration of the placebo: Oral use CONDITION: Colorectal cancer liver metastases ; MedDRA version: 20.0 Level: LLT Classification code 10007095 Term: Cancer of liver, secondary System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: The trial aims to determine whether oral IPE therapy, started at least 2 weeks before surgery and continued for a minimum of 2 years, improves colorectal cancer recurrence in patients undergoing liver resection surgery for colorectal cancer liver metastases. Primary end point(s): The primary endpoint is progression free survival (PFS) during a 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.; ; The date of clinical progression is defined as the date of the CT scan or relevant assessment at which disease progression or new recurrence is identified. This can be clinical progression or, for RECIST evaluable disease, radiological progression by RECIST principles. For participants who have clear clinical symptoms of disease progression without confirmatory imaging, the date of progression is defined as the date of the clinical assessment.; Secondary Objective: To determine whether IPE treatment improves survival.; ; To confirm the safety and tolerability of IPE before and after surgery, including during chemotherapy.; ; To determine whether IPE treatment improves quality of life after colorectal cancer liver metastasis surgery, as reported by participants.; ; To determine the cost effectiveness of IPE treatment.; ; To determine whether IPE treatment has an effect on the diagnosis of new cancers.; Timepoint(s) of evaluation of this end point: The primary endpoint is evaluated at every visit from visit 3 onwards. 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 metastasis with curative intent, including repeat ‘re‐do’ colorectal cancer liver metastasis liver surgery (a second independent resection for a separate colorectal cancer liver recurrence) • Intention to receive =2 weeks treatment with IMP prior to colorectal cancer liver metastasis surgery Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0 SECONDARY OUTCOME: Secondary end point(s): The secondary endpoints are:; • Overall Survival (OS), defined as the time from randomisation to death, from any cause (key secondary endpoint); • Safety and tolerability of IPE before and after CRCLM surgery, including during chemotherapy; • Patient reported quality of life, measured using the EQ‐5D, EORTC QLQ‐C30 and QLQ‐LMC21 questionnaires; • Cost‐effectiveness of IPE; • 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); ; The exploratory endpoints are:; • Red blood cell membrane EPA content, measured at baseline, surgery and 6 months after surgery (only patients from Leeds and Sheffield); • Change in lean body mass measured by CT scanning during follow up as assessed by the L3 skeletal muscle index score; Timepoint(s) of evaluation of this end point: Overall survival is evaluated at every visit from visit 2 onwards.; ; Safety and tolerability of IPE is evaluated at every visit from visit 2 onwards and at fornightly telephone calls with the research nurse between visit 1 and visit 2 and at the telephone call with the research nurse at 60 days after visit 10/exit visit.; ; Patient reported quality of life is collected at visit 1, visit 3 and all visits thereafter. ; ; Health economic data is collected at all visits and information on hospital resource activity will also be collected at fornightly telephone calls with the research nurse between visit 1 and visit 2.; ; Evaluation for new primary cancers will take place at every visit from visit 3 onwards.;