Examining the efficacy of faecal immunochemical testing (FIT) in patients with Lynch Syndrome
| ISRCTN | ISRCTN15740250 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15740250 |
| IRAS number | 280583 |
| Secondary identifying numbers | CPMS 48716, IRAS 280583 |
- Submission date
- 09/07/2021
- Registration date
- 13/07/2021
- Last edited
- 06/09/2023
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Lynch Syndrome (LS) is an inherited disorder that results in an increased lifetime risk of several cancers, including colorectal cancer (CRC). It is estimated that nearly 175,000 people in the U.K. have Lynch Syndrome, though fewer than 5% (~8,750) are known.
Given the increased risk of CRC for individuals with LS, colonoscopy (a test to check inside the bowels) is recommended every two years for patients with LS within England, which may begin between the ages of 25 – 35 and last until 75 years of age. Though colonoscopy is presently considered the gold standard for the detection of colonic lesions, the requirement of having up to 25 colonoscopies throughout a LS patient’s lifetime is invasive and resource intensive.
For this research study, we are proposing the use of a non-invasive, self-sampling diagnostic device known as the faecal immunochemical testing (FIT) kit for patients with LS. FIT is a CLIA-waived diagnostic device designed to detect trace amounts of faecal haemoglobin (f-Hb) and used to guide clinical referral for lower gastrointestinal investigation, often to colonoscopy. Despite the routine use of FIT in population-based CRC screening programmes within the U.K. and abroad, the role of FIT for patients with LS is unknown.
Who can participate?
Individuals (men and women) aged 25 – 75 years, who have a diagnosis of Lynch Syndrome.
What does the study involve?
In this study, we will offer eligible LS patients an OC-Sensor™ FIT kit via mail at baseline, and annually for 3 years thereafter. Patients will also receive additional study materials at baseline, as well as a pre-notification letter just prior to baseline. After the trial has ended, we will continue to passively observe a subset of trial participants (those with preceding negative FIT results), for the observation of interval CRC’s. The mechanism for collecting long-term follow up data at 3 years is dependent on future funding, however, and will therefore be decided at a later date.
What are the possible benefits and risks of participating?
By participating in this study there is a chance that your FIT results may provide your clinician with additional information which may assist them with your clinical care. You will also be contributing to research that will help improve surveillance for people with Lynch Syndrome in the future. There are no immediate risks in taking part in this research study, and it is unlikely that you will come to any harm while collecting a stool sample as part of the FIT kit sampling. FIT testing is used routinely as part of the National Bowel Cancer Screening Programme and has been deemed safe and effective in this setting. You may, however, be referred for an additional colonoscopy(s). Although this procedure is not considered as part of this research study, there are some risks associated with colonoscopies. Please enquire about any of these risks directly with your consultant.
Where is the study run from?
King's College London (UK)
When is the study starting and how long is it expected to run for?
March 2021 to August 2026
Who is funding the study?
1. MAST Group Ltd (UK)
2. 40TUDE Curing Colon Cancer (UK)
Who is the main contact?
Annie Lincoln
Dr Kevin Monahan
Prof Peter Sasieni
FITforLynchStudy@kcl.ac.uk
Contact information
Scientific
Cancer Prevention Group, School of Cancer & Pharmaceutical Sciences
King's College London
Research Oncology Seminar Room (GH0603004), 3rd Floor
Bermondsey Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
 ORCID ID |
0000-0002-6441-1445 |
|---|---|
| Phone | +44(0)20 7848 8187 |
| Annie.lincoln@kcl.ac.uk |
Scientific
Family Cancer Clinic & Wolfson Unit for Endoscopy
London North West University Healthcare NHS Trust
St Mark’s Hospital
Northwick Park
Watford Road
Harrow
HA1 3UJ
United Kingdom
| Phone | +44 (0)20 8235 4270 |
|---|---|
| k.monahan@nhs.net |
Scientific
King’s College London
Faculty of Life Sciences & Medicine
School of Cancer & Pharmaceutical Sciences & Medicine, Cancer Prevention Group
Innovation Hub
Guy’s Cancer Centre
Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
| Phone | +44 (0)20 7188 4484 |
|---|---|
| peter.sasieni@kcl.ac.uk |
Study information
| Study design | Observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Home |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Exploring the utility and acceptability of Faecal Immunochemical Testing (FIT) as a novel intervention for the improvement of Colorectal Cancer (CRC) surveillance in individuals with Lynch Syndrome |
| Study acronym | FIT for Lynch Syndrome |
| Study hypothesis | Based upon preliminary data which came from a preceding emergency clinical service evaluation examining the utility of FIT in patients with Lynch Syndrome throughout the COVID-19 pandemic, we believe that a structured programme and longitudinal research with annual FIT alongside biannual colonoscopy in this patient cohort will enable a robust dataset to examine the efficacy of FIT as an additive, non-invasive diagnostic modality for the purposes of surveillance in patients with Lynch Syndrome. |
| Ethics approval(s) | Approved 25/03/2021, Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)2071048083; bradfordleeds.rec@hra.nhs.uk), ref: 21/YH/0066 |
| Condition | Lynch Syndrome (hereditary non-polyposis colorectal cancer) |
| Intervention | A baseline mailing will be sent to eligible participants within 30 days of their next standard of care colonoscopy to include the following study materials and items: -A study invitation letter -A FIT kit (OC-Sensor brand) enclosed within a biospecimen sample bag -Consent form -FIT instruction sheet (to have pictorial and written instructions for collection) -A baseline questionnaire -A patient information sheet -Return envelope w/ prepaid postage Eligible patients may read about the study in greater detail within the study invitation letter and the patient information leaflet. Interested patients will then be asked to provide a small faecal sample within the provided FIT kit and per the enclosed FIT instruction sheet. Additionally, they will be asked to complete the consent form and baseline questionnaire (which will assess attitudes of acceptability and preferences for this novel intervention, as well as current medications), all of which will be returned to the NHS Bowel Cancer Screening Programme Southern Hub (referred to as the "Southern Hub" herein), in Guildford, Surrey via the provided return envelope with prepaid postage. FIT (self-sampling) kits will be posted to enrolled patients annually for 3 years after baseline (Years 1-3) and will include the FIT kit for sample collection, the FIT instruction sheet, a post-baseline letter, and a return envelope with prepaid postage for return to the Southern Hub. At intervening years between patient's routine (biennial) colonoscopy (years 1 & 3), FIT will be used to inform colonoscopy triage for patients whose result exceeds an upper threshold of 6 micrograms of haemoglobin per gram of faeces. For patients whose FIT result exceeds the pre-defined upper threshold at those intervening years (whom we expect to be a small minority), results will be disclosed via their physician (Co-I) and they will be advised to proceed with a colonoscopy which shall be triaged via the two-week wait (2WW) pathway. A subset of FIT-negative patients will be passively followed-up 3 years after the trial ends for the observation of interval CRC's. To address the primary aim of the study, we will compare results from FIT and the respective pathology and/or histology reports from endoscopy following each colonoscopy from baseline through the subsequent 3 years (4 years total). |
| Intervention type | Other |
| Primary outcome measure | Confirmation of no visible CRC at time of colonoscopy and subsequent negative pathology report for patients who had preceding negative FIT results. The absence of colorectal cancer is measured by colonoscopy for participants with preceding negative FIT results (<6 micrograms of haemoglobin / g of faeces) at Baseline and Year 2 |
| Secondary outcome measures | 1. The overall acceptability of this novel intervention (FIT) by this patient population (Lynch Syndrome) will be measured through the use of a participant questionnaire which will be distributed at baseline 2. Confirmation of colorectal neoplasia (CN) at time of colonoscopy, and subsequent confirmation via pathology report for patients who had preceding positive FIT results over the 3-year interventional follow-up period 3. Gut microbiota measured using 16S next-generation sequencing on residual DNA from archived FIT samples at a single time point 4. Colorectal cancer (CRC) diagnoses from patient records in a subset of patients who had negative FIT results at Baseline and Years 1-3 to record for potential interval cancers through Baseline, Years 1-3, and passive follow-up years 4-6 5. Advanced colorectal neoplasia (ACN) at time of colonoscopy, and subsequent confirmation of malignancy on pathology report using patient records over the 5 year follow up period |
| Overall study start date | 25/03/2021 |
| Overall study end date | 31/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 25 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 400; UK Sample Size: 400 |
| Total final enrolment | 339 |
| Participant inclusion criteria | 1. Individuals (men and women) who have a diagnosis of Lynch Syndrome (as defined by a confirmed mutation in any of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2 or EPCAM), 2. Between the age of 25 - 75 years 3. Have a scheduled standard of care (SOC) routine colonoscopy appointment within the 12 months at start of study recruitment |
| Participant exclusion criteria | 1. Individuals who have not had genetic testing and therefore are not known to have Lynch Syndrome 2. Individuals who have previously undergone a subtotal or total colectomy 3. Individuals unable to provide informed consent |
| Recruitment start date | 06/09/2021 |
| Recruitment end date | 31/08/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Harrow
HA1 3UJ
United Kingdom
Great Maze Pond
London
SE1 9RT
United Kingdom
High Heaton
Newcastle
NE7 7DN
United Kingdom
London
SW17 0QT
United Kingdom
Chelsea
London
SW3 6JJ
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Birmingham
B4 6NH
United Kingdom
Oxford
OX3 9DU
United Kingdom
Sponsor information
Hospital/treatment centre
Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
England
United Kingdom
| Phone | +44 (0)20 8869 5829 |
|---|---|
| Lnwh-tr.Research@nhs.net | |
| Website | http://www.lnwh.nhs.uk/ |
"ROR" |
https://ror.org/04cntmc13 |
Funders
Funder type
Industry
No information available
No information available
Results and Publications
| Intention to publish date | 31/08/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | The preliminary findings (from baseline mailings. subsequent endoscopy procedures, and the participant questionnaire) will be analysed by the lead Project Manager and PhD student associated with this research study, Annie Lincoln, as part of her PhD thesis with King’s College London. Moreover, the study team plans to publish findings from this study within a high-impact, peer-reviewed journal(s), for the purposes of internal report(s) for the NHS and participating endoscopy suites, and to present at future conferences. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 07/11/2022 | 08/11/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 05/09/2023 | 06/09/2023 | Yes | No |
Editorial Notes
06/09/2023: Publication reference and total final enrolment added.
06/03/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2023 to 31/08/2027.
2. The overall end date was changed from 31/12/2025 to 31/08/2026.
3. The intention to publish date was changed from 31/12/2026 to 31/08/2027.
4. The plain English summary was updated to reflect these changes.
08/11/2022: Publication reference added.
01/09/2022: The recruitment end date has been changed from 16/09/2022 to 31/03/2023.
02/11/2021: The following changes have been made:
1. The recruitment end date has been changed from 16/08/2022 to 16/09/2022.
2. The individual participant data (IPD) sharing statement has been added.
02/09/2021: The recruitment start date was changed from 01/09/2021 to 06/09/2021.
04/08/2021: The recruitment start date was changed from 16/08/2021 to 01/09/2021.
09/07/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
