A Study of the Effect of Gemcitabine With Fish Oil in Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Over 7000 patients are diagnosed with pancreas cancer every year in the UK. Only 10% have it caught early enough to have surgery to cure it. The rest at best can undergo chemotherapy to extend survival, but current treatments offer at best an improvement of only a few months compared to no treatment at all. In addition only about a quarter of patients will respond to the treatment. In addition these patients often experience profound weight loss, loss of appetite and energy primarily because of the cancer process itself. Our hypothesis is that the addition of fish oil infusion to gemcitabine chemotherapy will result in an improved rate of tumour response on CT imaging. Fish oils, or specifically the omega-3 fatty acid component, appear to have a range of powerful anti-cancer actions. This is supported by evidence from a wide range of sources, from laboratory experiments to basic human studies. Although this evidence specifically includes many pancreatic cancer studies in the laboratory it has not yet been confirmed in human trials. Contrary to conventional chemotherapy, fish oil is a naturally occuring non-toxic compound and so is not associated with the side-effects of chemotherapy. In fact a number of clinical studies have demonstrated significant improvements in quality of life for pancreas cancer patients treated with fish oil, particularly with reference to improvements in appetite and energy levels. This is of course in addition to the anti-cancer actions.

Detailed Description
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Our trial will involve recruiting patients who have unresectable pancreatic cancer and who are suitable for the current standard of care which is gemcitabine chemotherapy. They will be assessed for suitability and then offered entry into the trial. This essentially consists of a 4 hour long infusion of purified omega-3 fish oil immediately after their gemcitabine chemotherapy has finished. This will occur once a week for three weeks, with a rest on the fourth week. The cycle then continues until the cancer has shown progression on a CT scan, the gemcitabine chemotherapy is stopped due to toxicity or the patient withdraws or dies. CT scans to assess this are performed every 2 months. Blood tests will be taken before and after each treatment and analysed for changes in inflammatory markers. The patients will be asked to fill in a quality of life and pain questionnaire each week during the 4 hour infusion.

Official Title
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Phase II Trial of the Effect of Gemcitabine With Intravenous Omega-3 Fish Oil Infusion in Patients With Unresectable Pancreatic Adenocarcinoma

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: Lipidem fish oil infusion + Gemcitabine chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >18 years Able to give informed written consent ECOG performance status of 0 or 1 (Appendix 1) Life expectancy >12 weeks Adequate hepatic and renal function documented within 14 days prior to treatment AST and ALT ≤2.5x upper limit of normal (ULN), unless liver metastases present, in which case ≤5.0xULN Total bilirubin ≤2.5xULN Serum creatinine ≤1.5xULN or calculated creatinine clearance ≥60ml/min Urinary protein <1+ by urine dipstick. If ≥1+, then 24-hour urine collection should be done and may only be enrolled if urine protein is <2g/24hours Adequate bone marrow function Haemoglobin ≥9g/dL (can have transfusion or growth factors) Platelets ≥100,000cells/mm3 Neutrophil count ≥1500cells/mm3 No significant hyperlipidaemia Patients without severe blood coagulation disorders (anticoagulants allowed) Women of childbearing age must have a negative pregnancy test (urine or serum) at commencement of treatment Willingness to comply with scheduled visits, treatment, laboratory test, and other aspects of the trial Exclusion Criteria: Prior treatment with any systemic chemotherapy for metastatic disease Prior adjuvant radio- or chemotherapy within 4 weeks of starting the study Previous treatment with gemcitabine Hypersensitivity to fish-, egg-, or soy protein, or to any of the active substances or constituents in the lipid emulsion Any general contra-indications to infusion therapy - pulmonary oedema, hyperhydration, decompensated cardiac insufficiency Any unstable medical conditions - uncontrolled diabetes mellitus, acute myocardial infarction, stroke, embolic disease, metabolic acidosis, sepsis, pancreatitis Known HIV or AIDS Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with requirements of the protocol History of malignancy other than pancreatic cancer, with the exception of curative treatment for skin cancer (other than melanoma) or in situ breast or cervical carcinoma, or those treated with curative intent for any other cancer with no evidence of disease for 5 years Major surgical procedure or significant traumatic injury within 4 weeks of treatment Female patients must be surgically sterilised or postmenopausal or agree to use two adequate contraception measures during the period of therapy and continued for 6 months after the last dose of gemcitabine. Male patients must be surgically sterilised or agree to use adequate contraception for the same period. Patients deemed unsuitable for gemcitabine chemotherapy

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>All patients entering the trial | Drug: Lipidem fish oil infusion + Gemcitabine chemotherapy<br>* 500mls intravenous infusion once a week of lipidem in addition to standard starting dose of gemcitabine (1000mg/m2) Dose can be reduced if poorly tolerated<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete and partial response) on CT according to RECIST criteria |  | Every 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | measured once for each patient | 
| Progression free survival |  | Measured once for each patient | 
| Safety / tolerability of fish oil and gemcitabine |  | weekly | 
| Quality of life scores |  | weekly | 
| brief pain inventory scores |  | weekly | 
| Pharmacokinetic analysis of blood samples |  | weekly (before and after treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic, carcinoma, cancer, fish, alternative