Physiological Effects of Altering Cancer-related Inflammation

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Aspirin
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin<br>20 patients randomised to aspirin 75mg PO once daily | Drug: Aspirin<br> <br> |
| Active Comparator: Ibuprofen<br>20 patients randomised to ibuprofen 400mg PO three times daily | Drug: Ibuprofen<br> <br> |
| No Intervention: Control<br>20 patients randomised to receive no treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Approx 4 weeks (post-treatment and surgery) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon, cancer, NSAID, inflammation