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

Primary Purpose

Pancreatic Neoplasms

Status

Completed

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Lipidem fish oil infusion + Gemcitabine chemotherapy

About this trial

This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring pancreatic, carcinoma, cancer, fish, alternative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospitals of Leicester : Leicester Royal Infirmary

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm Description

All patients entering the trial

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival

Progression free survival

Safety / tolerability of fish oil and gemcitabine

Quality of life scores

brief pain inventory scores

Pharmacokinetic analysis of blood samples

Full Information

NCT ID

NCT01019382

First Posted

October 27, 2009

Last Updated

December 3, 2014

Sponsor

University Hospitals, Leicester

Collaborators

B. Braun Medical Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01019382

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospitals, Leicester

Collaborators

B. Braun Medical Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Neoplasms

Keywords

pancreatic, carcinoma, cancer, fish, alternative

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All patients

Arm Type

Experimental

Arm Description

All patients entering the trial

Intervention Type

Drug

Intervention Name(s)

Lipidem fish oil infusion + Gemcitabine chemotherapy

Other Intervention Name(s)

Gemzar

Intervention Description

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 Measure Information:

Title

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

Time Frame

Every 2 months

Secondary Outcome Measure Information:

Title

Overall survival

Time Frame

measured once for each patient

Title

Progression free survival

Time Frame

Measured once for each patient

Title

Safety / tolerability of fish oil and gemcitabine

Time Frame

weekly

Title

Quality of life scores

Time Frame

weekly

Title

brief pain inventory scores

Time Frame

weekly

Title

Pharmacokinetic analysis of blood samples

Time Frame

weekly (before and after treatment)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ashley Dennison, MD FRCS

Organizational Affiliation

University Hospitals, Leicester

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

William Steward, Phd FRCP

Organizational Affiliation

University Hospitals, Leicester

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Matthew Metcalfe, MA MD FRCS

Organizational Affiliation

University Hospitals, Leicester

Official's Role

Study Chair

Facility Information:

Facility Name

University Hospitals of Leicester : Leicester Royal Infirmary

City

Leicester

State/Province

Leicestershire

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

19723085

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.

Results Reference

background

PubMed Identifier

19667153

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

Results Reference

background

PubMed Identifier

19493674

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.

Results Reference

background

PubMed Identifier

18437081

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.

Results Reference

background

PubMed Identifier

17896154

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. doi: 10.1245/s10434-007-9556-8. Epub 2007 Sep 26.

Results Reference

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PubMed Identifier

16201853

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. doi: 10.1207/s15327914nc5202_12.

Results Reference

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PubMed Identifier

16157238

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. doi: 10.1016/j.nut.2004.12.013.

Results Reference

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PubMed Identifier

15361649

Citation

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.

Results Reference

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PubMed Identifier

23458624

Citation

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.

Results Reference

derived

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

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