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

NCT ID: NCT01019382

Last Updated: 2014-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-06-30

Brief 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.

Detailed 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.

Conditions

Pancreatic Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All patients

All patients entering the trial

Group Type: EXPERIMENTAL

Lipidem fish oil infusion + Gemcitabine chemotherapy

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Gemzar

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

B. Braun Medical Inc.

INDUSTRY

Sponsor Role: collaborator

University Hospitals, Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashley Dennison, MD FRCS

Role: PRINCIPAL_INVESTIGATOR

University Hospitals, Leicester

William Steward, Phd FRCP

Role: STUDY_DIRECTOR

University Hospitals, Leicester

Matthew Metcalfe, MA MD FRCS

Role: STUDY_CHAIR

University Hospitals, Leicester

Locations

University Hospitals of Leicester : Leicester Royal Infirmary

Leicester, Leicestershire, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 19723085 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19667153 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19493674 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18437081 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17896154 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16201853 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16157238 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15361649 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23458624 (View on PubMed)

Other Identifiers

EudraCT number 2009-009470027

Identifier Type: -

Identifier Source: secondary_id

UHL trial number 10720

Identifier Type: -

Identifier Source: secondary_id

09/H0408/51

Identifier Type: -

Identifier Source: org_study_id