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

Pancreatic Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01019382
• Other study ID #: 09/H0408/51
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 2
• First received: October 27, 2009
• Last updated: December 3, 2014
• Start date: October 2009
• Est. completion date: June 2014

Study information

• Verified date: December 2014
• Source: University Hospitals, Leicester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United Kingdom	University Hospitals of Leicester : Leicester Royal Infirmary	Leicester	Leicestershire

Sponsors (2)

Lead Sponsor	Collaborator
University Hospitals, Leicester	B. Braun Medical Inc.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

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. Review. — View Citation

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 Mar;30(3):1033. Anticancer Res.2010 Jan;30(1):277. — View Citation

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. — View Citation

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. Epub 2007 Sep 26. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (complete and partial response) on CT according to RECIST criteria		Every 2 months	No
Secondary	Overall survival		measured once for each patient	No
Secondary	Progression free survival		Measured once for each patient	No
Secondary	Safety / tolerability of fish oil and gemcitabine		weekly	Yes
Secondary	Quality of life scores		weekly	No
Secondary	brief pain inventory scores		weekly	No
Secondary	Pharmacokinetic analysis of blood samples		weekly (before and after treatment)	No