Physiological Effects of Altering Cancer-related Inflammation

Colon Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01786200
• Other study ID #: GN12SU401
• Secondary ID: 12736
• Status: Not yet recruiting
• Phase: N/A
• First received: January 29, 2013
• Last updated: February 5, 2013
• Start date: February 2013

Study information

• Verified date: February 2013
• Source: NHS Greater Glasgow and Clyde
• Contact: James Park
• Phone: 0141 211 4870
• Email: james.park[@]glasgow.ac.uk
• Is FDA regulated: No
• Health authority: UK: N/A - not a CTIMP
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Colon Cancer

Intervention

Drug:
• Aspirin

• Ibuprofen

Locations

Country	Name	City	State
United Kingdom	Glasgow Royal Infirmary - Walton Building	Glasgow

Sponsors (3)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Academy of Medical Sciences, Wellcome Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	Assessment of gene inflammatory profile		Approx 4 weeks (post-treatment and surgery)	No
Secondary	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)	No