A Study Of The Effect Of Gemcitabine With Fish Oil In Patients With Advanced Pancreatic Cancer

Study Overview

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

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.

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.

Pancreatic Neoplasms

DRUG: Lipidem fish oil infusion + Gemcitabine chemotherapy

09/H0408/51
EudraCT number 2009-009470027
UHL trial number 10720

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-10-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-12-03
First Submitted that Met QC Criteria 2009-11-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-12-04
First Posted (ESTIMATED) 2009-11-25	Results First Posted N/A	Last Verified 2014-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: All patients All patients entering the trial	DRUG: Lipidem fish oil infusion + Gemcitabine chemotherapy 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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: All patients

All patients entering the trial

DRUG: Lipidem fish oil infusion + Gemcitabine chemotherapy

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

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

Secondary Outcome Measures	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)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

B. Braun Medical Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Ashley Dennison, MD FRCS, University Hospitals, Leicester

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Park KS, Lim JW, Kim H. Inhibitory mechanism of omega-3 fatty acids in pancreatic inflammation and apoptosis. Ann N Y Acad Sci. 2009 Aug;1171:421-7. doi: 10.1111/j.1749-6632.2009.04887.x.
Chiang KC, Persons KS, Istfan NW, Holick MF, Chen TC. Fish oil enhances the antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 on liver cancer cells. Anticancer Res. 2009 Sep;29(9):3591-6. Erratum In: Anticancer Res.2010 Jan;30(1):277. Anticancer Res.2010 Mar;30(3):1033.
Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer. 2009 Aug;45(12):2077-86. doi: 10.1016/j.ejca.2009.04.026. Epub 2009 Jun 1.
Funahashi H, Satake M, Hasan S, Sawai H, Newman RA, Reber HA, Hines OJ, Eibl G. Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth. Pancreas. 2008 May;36(4):353-62. doi: 10.1097/MPA.0b013e31815ccc44.
Hering J, Garrean S, Dekoj TR, Razzak A, Saied A, Trevino J, Babcock TA, Espat NJ. Inhibition of proliferation by omega-3 fatty acids in chemoresistant pancreatic cancer cells. Ann Surg Oncol. 2007 Dec;14(12):3620-8. doi: 10.1245/s10434-007-9556-8. Epub 2007 Sep 26.
Merendino N, Loppi B, D'Aquino M, Molinari R, Pessina G, Romano C, Velotti F. Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation. Nutr Cancer. 2005;52(2):225-33. doi: 10.1207/s15327914nc5202_12.
Shirota T, Haji S, Yamasaki M, Iwasaki T, Hidaka T, Takeyama Y, Shiozaki H, Ohyanagi H. Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid. Nutrition. 2005 Oct;21(10):1010-7. doi: 10.1016/j.nut.2004.12.013.
Brown TT, Zelnik DL, Dobs AS. Fish oil supplementation in the treatment of cachexia in pancreatic cancer patients. Int J Gastrointest Cancer. 2003;34(2-3):143-50. doi: 10.1385/IJGC:34:2-3:143.
Arshad A, Chung WY, Steward W, Metcalfe MS, Dennison AR. Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil. HPB (Oxford). 2013 Jun;15(6):428-32. doi: 10.1111/hpb.12002. Epub 2012 Nov 22.

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