Physiological Effects of Altering Cancer-related Inflammation
Primary Purpose
Colon Cancer
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Aspirin
Ibuprofen
Sponsored by
About this trial
This is an interventional basic science trial for Colon Cancer focused on measuring colon, cancer, NSAID, inflammation
Eligibility Criteria
Inclusion Criteria:
- aged 18 to 75 years old
- histologically confirmed colon cancer
- evidence of systemic inflammation (C-reactive protein >10mg/l)
- candidate for elective primary curative resection
Exclusion Criteria:
- Age <18yrs or >75yrs
- emergency presentation
- rectal cancer
- distal metastatic disease at presentation
- provision of neo-adjuvant chemo-radiotherapy
- long-term use of aspirin or anti-inflammatory medications (NSAIDS, or steroids
- hypersensitivity to product or excipients or evidence of previous hypersensitivity reactions such as asthma, rhinitis, angioedema or urticaria in response to aspirin, ibuprofen or other NSAID
- intolerance of NSAIDs/ aspirin due to allergy or side effects
- active peptic ulcer disease
- previous history of recurrent gastrointestinal bleeding or bleeding/perforation secondary to previous NSAID use
- previous treatment for gastrointestinal cancer
- alcohol excess (above recommended guidelines)
- chronic renal impairment
- moderate to severe heart failure
- hepatic impairment
Sites / Locations
- Glasgow Royal Infirmary - Walton Building
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
No Intervention
Arm Label
Aspirin
Ibuprofen
Control
Arm Description
20 patients randomised to aspirin 75mg PO once daily
20 patients randomised to ibuprofen 400mg PO three times daily
20 patients randomised to receive no treatment
Outcomes
Primary Outcome Measures
Klintrup-Makinen immune score
To evaluate the local inflammatory effects associated with down-regulation of the systemic inflammatory response prior to curative surgery as measured by Klintrup-Makinen immune score
Secondary Outcome Measures
Systemic inflammatory response
Comprehensive assessment of the systemic inflammatory response prior to curative surgery as measured by C-reactive protein (CRP), differential white cell count, albumin and cytokines (IL-1, 6,8 and 10, TNF-alpha)
Assessment of gene inflammatory profile
Local inflammatory response
Immunohistochemical analysis of immune cells infiltrates in colonic and tumour tissue will be performed quantitatively. Cell surface antigens evaluated include CD4+, CD8+, CD68+, CD45RO+ and FOXP3+.
Full Information
NCT ID
NCT01786200
First Posted
January 29, 2013
Last Updated
February 5, 2013
Sponsor
NHS Greater Glasgow and Clyde
Collaborators
Academy of Medical Sciences, Wellcome Trust
1. Study Identification
Unique Protocol Identification Number
NCT01786200
Brief Title
Physiological Effects of Altering Cancer-related Inflammation
Official Title
Pilot Study to Investigate the Physiological Effects Associated With Down-regulation of Host-tumour Inflammatory Responses in Colon Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Unknown status
Study Start Date
February 2013 (undefined)
Primary Completion Date
December 2014 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NHS Greater Glasgow and Clyde
Collaborators
Academy of Medical Sciences, Wellcome Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This prospective pilot study will examine whether the previously reported effects of NSAIDs on colorectal cancer may be modulated through alterations in tissue gene expression, up regulation of local immune cell infiltrates or down-regulation of the systemic inflammatory response.
Detailed Description
Bowel cancer is the second commonest cause of death from cancer in the UK. Of patients who have an apparently curative operation, half unfortunately suffer disease recurrence and die before 5 years. Clearly more research is required to improve outcomes in this condition. Most current research focuses on antitumour strategies, however the reaction of the patient (host) to the tumour is also important. The host inflammatory responses to the cancer are likely to represent part of this host-tumour relationship. Inflammation plays an important role in predicting patients who will die. Currently it is not known whether antiinflammatory drugs have any effect on cancer related inflammation detected in the blood or in/around the tumour.
Aims: We hope to demonstrate that tumour related inflammation in bowel cancer can be altered using anti- inflammatory drugs. This may form the rationale for the use of antiinflammatory drugs to improve prognosis in colorectal cancer patients undergoing surgery.
Methods: This pilot study will investigate whether simple antiinflammatory drugs can alter markers of inflammation both in the blood and in/around the tumour. Patients having bowel cancer surgery will be prescribed one of two anti-inflammatory drugs (aspirin 75mg once daily or ibuprofen 400mg three times daily) for 2 to 3 weeks prior to their operation. Blood and tumour samples before and after the treatment will be analysed.
If the study's aims are met and cancer-related inflammation can be altered prior to surgery, then a larger scale drug trial will be proposed to demonstrate reduced cancer recurrence and improved survival.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer
Keywords
colon, cancer, NSAID, inflammation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Aspirin
Arm Type
Active Comparator
Arm Description
20 patients randomised to aspirin 75mg PO once daily
Arm Title
Ibuprofen
Arm Type
Active Comparator
Arm Description
20 patients randomised to ibuprofen 400mg PO three times daily
Arm Title
Control
Arm Type
No Intervention
Arm Description
20 patients randomised to receive no treatment
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Primary Outcome Measure Information:
Title
Klintrup-Makinen immune score
Description
To evaluate the local inflammatory effects associated with down-regulation of the systemic inflammatory response prior to curative surgery as measured by Klintrup-Makinen immune score
Time Frame
Approx 4 weeks (post-treatment and surgery)
Secondary Outcome Measure Information:
Title
Systemic inflammatory response
Description
Comprehensive assessment of the systemic inflammatory response prior to curative surgery as measured by C-reactive protein (CRP), differential white cell count, albumin and cytokines (IL-1, 6,8 and 10, TNF-alpha)
Time Frame
Approx 4 weeks (post-treatment and surgery)
Title
Assessment of gene inflammatory profile
Time Frame
Approx 4 weeks (post-treatment and surgery)
Title
Local inflammatory response
Description
Immunohistochemical analysis of immune cells infiltrates in colonic and tumour tissue will be performed quantitatively. Cell surface antigens evaluated include CD4+, CD8+, CD68+, CD45RO+ and FOXP3+.
Time Frame
Approx 4 weeks (post-treatment and surgery)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
aged 18 to 75 years old
histologically confirmed colon cancer
evidence of systemic inflammation (C-reactive protein >10mg/l)
candidate for elective primary curative resection
Exclusion Criteria:
Age <18yrs or >75yrs
emergency presentation
rectal cancer
distal metastatic disease at presentation
provision of neo-adjuvant chemo-radiotherapy
long-term use of aspirin or anti-inflammatory medications (NSAIDS, or steroids
hypersensitivity to product or excipients or evidence of previous hypersensitivity reactions such as asthma, rhinitis, angioedema or urticaria in response to aspirin, ibuprofen or other NSAID
intolerance of NSAIDs/ aspirin due to allergy or side effects
active peptic ulcer disease
previous history of recurrent gastrointestinal bleeding or bleeding/perforation secondary to previous NSAID use
previous treatment for gastrointestinal cancer
alcohol excess (above recommended guidelines)
chronic renal impairment
moderate to severe heart failure
hepatic impairment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James Park
Phone
0141 211 4870
Email
james.park@glasgow.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Campbell Roxburgh
Organizational Affiliation
University of Glasgow
Official's Role
Principal Investigator
Facility Information:
Facility Name
Glasgow Royal Infirmary - Walton Building
City
Glasgow
ZIP/Postal Code
G4 0SF
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Park
First Name & Middle Initial & Last Name & Degree
Campbell Roxburgh
12. IPD Sharing Statement
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Physiological Effects of Altering Cancer-related Inflammation
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