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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
NHS Greater Glasgow and Clyde
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Colon Cancer focused on measuring colon, cancer, NSAID, inflammation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

First Posted
January 29, 2013
Last Updated
February 5, 2013
Sponsor
NHS Greater Glasgow and Clyde
Collaborators
Academy of Medical Sciences, Wellcome Trust
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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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