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

NCT01019382 | Completed Phase 2

• 3 other identifiers: 09/H0408/51EudraCT number 2009-009470027UHL trial number 10720
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Neoplasms

Keywords

pancreatic; carcinoma; cancer; fish; alternative

Outcome Measures

Primary Outcomes (1)

• Objective response rate (complete and partial response) on CT according to RECIST criteria

  Every 2 months

Secondary Outcomes (6)

• 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

Study Arms (1)

All patients

EXPERIMENTAL

All patients entering the trial

Drug: Lipidem fish oil infusion + Gemcitabine chemotherapy

Interventions

Lipidem fish oil infusion + Gemcitabine chemotherapy 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

Also known as: Gemzar

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals, Leicester: lead
• B. Braun Medical Inc.: collaborator

Study Sites (1)

University Hospitals of Leicester : Leicester Royal Infirmary

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Related Publications (9)

• 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.

  PMID: 19723085 BACKGROUND

• 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.

  PMID: 19667153 BACKGROUND

• 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.

  PMID: 19493674 BACKGROUND

• 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.

  PMID: 18437081 BACKGROUND

• 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.

  PMID: 17896154 BACKGROUND

• 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.

  PMID: 16201853 BACKGROUND

• 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.

  PMID: 16157238 BACKGROUND

• 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.

  PMID: 15361649 BACKGROUND

• 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.

  PMID: 23458624 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma; Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Ashley Dennison, MD FRCS

  University Hospitals, Leicester

  PRINCIPAL INVESTIGATOR

• William Steward, Phd FRCP

  University Hospitals, Leicester

  STUDY DIRECTOR

• Matthew Metcalfe, MA MD FRCS

  University Hospitals, Leicester

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2009
• First Posted: November 25, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 4, 2014

Record last verified: 2014-12

Locations

GB (1)