Clinical trial NCT01786200: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Colon Cancer
Keywords: colon
cancer
NSAID
inflammation
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: Academy of Medical Sciences
name: Wellcome Trust
First posted: 2013-02-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Klintrup-Makinen immune score
timeFrame: Approx 4 weeks (post-treatment and surgery)
Secondary outcomes:
measure: Systemic inflammatory response
timeFrame: Approx 4 weeks (post-treatment and surgery)
measure: Assessment of gene inflammatory profile
timeFrame: Approx 4 weeks (post-treatment and surgery)
measure: Local inflammatory response
timeFrame: Approx 4 weeks (post-treatment and surgery)
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary - Walton Building
Study officials:
affiliation: University of Glasgow
name: Campbell Roxburgh
role: PRINCIPAL_INVESTIGATOR
References: