Eicosapentaenoic Acid (EPA) for Treatment of Colorectal Cancer Liver Metastases (EMT)

The Effects of Eicosapentaenoic Acid (EPA) on Biomarkers of Growth and Vascularity in Human Colorectal Cancer Liver Metastases (The EPA for Metastasis Trial)

Eicosapentaenoic acid (EPA) is a naturally occuring omega-3 polyunsaturated fatty acid found in oily fish. EPA has anti-colorectal (bowel) cancer activity in experimental models. This trial will test whether EPA reduces markers of tumour growth, and is safe and well tolerated,in patients with colorectal cancer liver metastases awaiting surgery.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Eicosapentaenoic acid free fatty acid

Detailed Description

A double-blind, randomised, placebo-controlled trial of eicosapentaenoic acid (EPA), in the free fatty acid form, 2g daily in patients who will undergo liver resection surgery for colorectal cancer liver metastases.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Leeds Institute of Molecular Medicine, St James's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than or equal to 18 years
• Either sex
• Liver resection deemed clinically appropriate for management of metastatic colorectal cancer
• Duration between decision to perform liver resection and surgery greater than 2 weeks
• Ability to give written informed consent and follow study protocol
• Telephone contact possible

Exclusion Criteria:

• Neo-adjuvant chemotherapy for colorectal cancer (CRC) liver metastasis
• Chemotherapy for any cancer in the previous 3 months
• Known bleeding diathesis or anticoagulation therapy
• Fish or seafood allergy
• Use of fish oil supplements (eg. cod liver oil) and unwilling to stop for the duration of the study
• Pregnancy
• Non-aspirin non-steroidal anti-inflammatory (NSAID) or corticosteroid use
• Renal impairment (serum creatinine >150)
• Active inflammatory disease (e.g. Inflammatory Bowel Disease, Rheumatoid Arthritis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 2 capsules twice daily	Drug: Placebo; 2 capsules taken twice daily for 2-6 weeks before liver resection.
Active Comparator: Eicosapentaenoic acid free fatty acid; 2g daily (2 x 500mg capsules twice daily)	Drug: Eicosapentaenoic acid free fatty acid; An enteric-coated preparation of 99% pure omega-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid as the free fatty acid. 500mg capsules, 2 taken twice daily for 2-6 weeks before liver resection.; Other Names: ALFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Histological Ki67 cancer cell proliferation index	at surgery 2-6 weeks after randomisation

Secondary Outcome Measures

Outcome Measure	Time Frame
Histological neo-CK18 cancer cell apoptosis index	at surgery 2-6 weeks after randomisation
Histological tumour CD31-positive cell microvessel density	at surgery 2-6 weeks after randomisation
Safety and tolerability of EPA treatment	Every 2 weeks whilst patient is taking study medication
Metastatic tissue and healthy liver tissue fatty acid composition and prostaglandin levels	at surgery 2-6 weeks after randomisation
Plasma markers of prostaglandin metabolism	1. Baseline 2. after approx 4 weeks of study medication (immediately prior to surgery). 3. Six weeks after liver resection (no study medication)
Platelet aggregation	1. Baseline 2. after approx 4 weeks of study medication (immediately prior to surgery). 3. Six weeks after liver resection (no study medication)
Urinary markers of prostaglandin metabolism	1. Baseline 2. after 2 weeks of study medication 3. after approx 4 weeks of study medication (immediately prior to surgery). 4. Six weeks after liver resection (no study medication)

Collaborators and Investigators

• Sponsor: University of Leeds
• Investigators: Principal Investigator: Mark A Hull, PhD, FRCP, Leeds Institute of Molecular Medicine, University of Leeds

Publications and helpful links

General Publications

• Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, Loadman PM, Toogood GJ, Hull MA. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut. 2014 Nov;63(11):1760-8. doi: 10.1136/gutjnl-2013-306445. Epub 2014 Jan 27.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 12, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): October 21, 2011
• Last Update Submitted That Met QC Criteria: October 20, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Colorectal Neoplasms; Liver Metastases; Eicosapentaenoic Acid; Randomised Controlled Trial; Fatty Acids, Omega-3; Fish Oils
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: GA09/9094; 2009-015903-22 (EudraCT Number)