Title: CReST 2 - Colorectal Endoscopic Stenting Trial 2
Funder: Department of Health and Social Care

Abstract: Introduction Non resection rates for colorectal cancer in the UK are 40%. In nearly all cases the disease is incurable or the patient not fit for major surgery. About 15% of patients with colorectal cancer present as an emergency with large bowel obstruction and require emergency treatment. Surgery is associated with increased mortality rate, prolonged stay in hospital, need for stoma formation and reduced patient quality of life. Stenting is an effective means of achieving immediate relief of obstruction. In palliative patients the stent is left in situ indefinitely. In this group of patients complication rates are in excess of 30%. Stent design, uncovered versus covered may affect complication rates and quality of life. Design A blinded, multi-centre randomised controlled trial with an internal pilot to assess recruitment, of covered versus uncovered colonic stents. The patient and clinifian assessing responsible for follow-up will both be blinded. The primary outcome measure is Quality of Life at 3 months (QoL will measured regularly for the first year). Secondary outcome measures will be short & long term complication rates – migration, re-obstruction, perforation, time to onset of complications, complication rates on chemotherapy, survival rates to maximum of 2 years, success of endoscopic re intervention & stoma rates, cost effectiveness. Sample size The sample size is based on a primary outcome of QLQ-C30 global health score at 3 months. A 0.5 sd difference between groups would be clinically meaningful as recommended in (1). A value of 24 for the control group standard deviation is available in (4). Using 90% power and alpha = 0.05 (& including an extra 10% for crossover and dropout) gives a total sample size of 200. Setting 20 NHS hospitals within the UK. Target population Patients requiring a colorectal stent for the treatment of obstructing colorectal cancer, where the intention is to leave the stent in-situ. Inclusion criteria Patients suitable for stenting because of obstructing colorectal cancer with incurable disease or who are not fit enough to undergo resection of their cancer. Exclusion criteria Patients with impending or established perforation of the colon, patients unwilling to consent to the study, patients with low rectal cancer, patients being treated or considered for treatment with antiangiogenic drugs. Health Technology assessed A comparison of two colonic stent designs, covered and uncovered. Stenting has an established place in the management of obstructing colorectal cancer in the palliative setting. The only alternative effective treatment option is surgery which has high morbidity and mortality. There is insufficient knowledge to guide clinicians to which stent type to use. This technology is not subject to rapid change. HES data will be used to collect data on the number of hospital outpatient visits, A&E attendances & inpatient admissions for the relevant secondary outcomes being assessed. Project timetable Commence August 2015, 6 month set up, commence recruitment Feb 2016, 3 year recruitment period, 2 year follow up and 6 months analysis & write up. Expertise in the team Four applicants are investigators on the UK multi-centre CReST RCT; stenting as a bridge to surgery in obstructing colorectal cancer. The applicants have run stenting workshops. The other applicants are all senior members of a Clinical Trials Unit.

Lay abstract: The 2014 National Bowel Cancer Audit has shown that up to 40% of patients who develop colorectal cancer are either not fit enough to have the cancer removed surgically or the cancer is too advanced to cure. Treatment in these patients is called palliative and is aimed at prolonging life and maximising quality of life (in terms of well-being, health including fitness and sexual health). A significant proportion of patients with colorectal cancer present as an emergency, where the cancer has caused a blockage of their bowel. Unless the blockage is relieved, the bowel would perforate and the patient would develop peritonitis. Surgery to remove the obstruction, if performed, is associated with increased mortality rate, prolonged stay in hospital, increased need for stoma formation (whereby the bowel is brought to the surface of the abdominal wall and opened and bowel content is collected into a bag which covers the opening), reduced patient quality of life and patients are often unable to have chemotherapy treatment for their cancer. An alternative treatment to surgery for patients who present with a blockage is to insert a tube (stent) across the part of the bowel which is blocked. This is made of a special metal which expands when inserted into the body. The stent procedure is performed without the need for general anaesthetic, and when successful provides immediate relief of symptoms and avoids the need for surgery and the need for a stoma (colostomy or ileostomy). When a stent is inserted into patients who are too unfit for major surgery or the cancer is too advanced for surgery, the stent is left in the patient indefinitely. Survival in these palliative patients is improving and about half the patients receiving chemotherapy will survive 18 months to 2 years. How well the stent works affects the patient's quality of life. Unfortunately, stent related complications are common and occur in over one third of patients. The potential complications associated with stenting include perforation of the bowel, stent obstruction with recurrent blockage of the bowel and stent migration (the stent is displaced from the site of obstruction). Two designs of stent are in current use in the UK; uncovered stents are made of bare metal and covered stents have a plastic covering which is designed to reduce the chances of stent blockage. Currently there is insufficient information comparing the two stent designs in terms of relative risk of complications of each stent design as well as outcome related to patient's expectations and quality of life. This study is designed to test which stent design, the uncovered or covered stent, is best for patients treated for palliation. Patients will be randomised (like the toss of a coin) to receive either a covered or uncovered stent. Patients will be asked to complete Quality of Life questionnaires in accordance with specified research guidelines and data will be collected on stent related complications. The data will then be compared to determine which stent design is better for palliative patients. Once the results of the study are known, they will be published in journals and presented at scientific meetings. In this way, doctors who treat this condition will be informed about the results of the study and they can use this information to help in the management of their own patients.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS