Physiological Effects of Altering Cancer-related Inflammation

February 5, 2013 updated by: NHS Greater Glasgow and Clyde

Pilot Study to Investigate the Physiological Effects Associated With Down-regulation of Host-tumour Inflammatory Responses in Colon Cancer

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom, G4 0SF
        • Glasgow Royal Infirmary - Walton Building

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Aspirin
20 patients randomised to aspirin 75mg PO once daily
Drug: Aspirin
ACTIVE_COMPARATOR: Ibuprofen
20 patients randomised to ibuprofen 400mg PO three times daily
Drug: Ibuprofen
NO_INTERVENTION: Control
20 patients randomised to receive no treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Klintrup-Makinen immune score
Time Frame: Approx 4 weeks (post-treatment and surgery)
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
Approx 4 weeks (post-treatment and surgery)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systemic inflammatory response
Time Frame: Approx 4 weeks (post-treatment and surgery)
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)
Approx 4 weeks (post-treatment and surgery)
Assessment of gene inflammatory profile
Time Frame: Approx 4 weeks (post-treatment and surgery)
Approx 4 weeks (post-treatment and surgery)
Local inflammatory response
Time Frame: Approx 4 weeks (post-treatment and surgery)
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+.
Approx 4 weeks (post-treatment and surgery)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

Wellcome Trust
Academy of Medical Sciences

Investigators

  • Principal Investigator: Campbell Roxburgh, University of Glasgow

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (ANTICIPATED)

December 1, 2014

Study Registration Dates

First Submitted

January 29, 2013

First Submitted That Met QC Criteria

February 5, 2013

First Posted (ESTIMATE)

February 7, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

February 7, 2013

Last Update Submitted That Met QC Criteria

February 5, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN12SU401
  • 12736 (REGISTRY: UKCRN)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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