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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Eicosapentaenoic acid free fatty acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>2 capsules twice daily | Drug: Placebo<br>* 2 capsules taken twice daily for 2-6 weeks before liver resection.<br>|
| Active Comparator: Eicosapentaenoic acid free fatty acid<br>2g daily (2 x 500mg capsules twice daily) | Drug: Eicosapentaenoic acid free fatty acid<br>* 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.<br>* Other names: ALFA;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Neoplasms, Fish Oils, Fatty Acids, Omega-3, Eicosapentaenoic Acid, Liver Metastases, Randomised Controlled Trial