Feasibility study of lidocaine infusion during bowel cancer surgery for cancer outcome

ISRCTN	ISRCTN29594895
DOI	https://doi.org/10.1186/ISRCTN29594895
ClinicalTrials.gov (NCT)	NCT05250791
Clinical Trials Information System (CTIS)	2021-006185-20
Integrated Research Application System (IRAS)	1004491
Protocol serial number	21CX7298, IRAS 1004491, CPMS 52546
Sponsor	Chelsea and Westminster Hospital
Funder	National Institute for Health Research

Submission date: 21/01/2022
Registration date: 06/04/2022
Last edited: 20/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
In most patients, surgery is the main treatment for large bowel cancer. It can lead to a complete cure. Unfortunately, in some patients, cancer can come back after surgery.
Even before surgery, a small number of cancer cells from the tumour can move around the body. When the surgeon removes the tumour, more cancer cells can be released. The surgeon cannot help this even by being careful. The body can deal with these cells, but if there are lots of them, they can clump together (known as micrometastases), and this can cause cancer to spread.
Around the time of surgery, the body reacts to heal the wound. Sadly, this creates an environment that can encourage cancer cells to grow. Surgery can further reduce the body’s defence system to deal with this.
Lidocaine is a local anaesthetic drug. It is safe and widely used, such as at the dentists. Anaesthetists sometimes use it for patients during surgery for other indications such as pain. Scientists have found in laboratory and animal studies that lidocaine may prevent and kill micrometastases.
Researchers want to see if lidocaine can prevent bowel cancer recurrence and improve quality of life after surgery. However, they need a big study to see if lidocaine can do this in bowel cancer patients. Before they do this, though, they need to check that such a study can be done in practice. This is done by running a small study known as a feasibility study such as this study. This study aims to see how the future larger study can be done successfully. The researchers also want to find out if they can understand the science of how lidocaine might work in patients.

Who can participate?
Patients over the age of 18 years with stage 2 or 3 large bowel cancer who will have surgery to remove the cancer

What does the study involve?
The study will involve participants:
1. Being randomly allocated to receive lidocaine or a dummy treatment (placebo) into their bloodstream (an infusion). The researchers plan to give this infusion from the start of surgery until after the surgery for a total duration of 24 hours.
2. Answering questionnaires to measure their quality of life before surgery, at 6 and 12 months after surgery via telephone. This may take around 20 minutes. During the 6 and 12 months telephone call, the researchers will also ask about their health and wellbeing, such as if they had to see their GP, go back to the hospital, or change their social circumstances because of their cancer.
3. The researchers will look at their medical records to see if cancer comes back after a year.
4. Completing a feedback questionnaire on day 3 while in the hospital to see how they get on with the study processes.
5. Having an extra blood test before and during surgery, after they finish the lidocaine/placebo infusion and on day 3 after their surgery. The researchers will try to take this extra blood during their routine hospital blood test. This additional blood test is to help them understand the science of how lidocaine might work for cancer patients.

What are the possible benefits and risks of participating?
It is hoped that lidocaine may help to reduce bowel cancer recurrence and improve quality of life after cancer surgery. However, there may be no medical benefit from participation in this study. The information collected will help the researchers to set up a larger study to determine if lidocaine can benefit bowel cancer survival.
Any bowel surgery has potential risks. Taking part in this study will not change these risks. The researchers do not anticipate any adverse effects on participants’ overall recovery.
There is always a minimal risk of side effects or allergies when taking any medication. The dose and duration the researchers have chosen as recommended by an international expert group are unlikely to produce adverse effects. This risk will be like if people receive a local anaesthetic in any other way. Local anaesthetics such as lidocaine have been used every day in NHS hospitals and dentist practices for decades.
In the rare event of a patient showing a reaction, the infusion will be stopped immediately. The doctor looking after the patients will know and have experience managing this. There are drugs available for treatment. Patients are not expected to have late side effects after the treatment has been stopped.
The rare reactions may include:
1. Allergic reaction (including rash, swelling, and blistering)
2. Tingling of the mouth and/or tongue
3. Ringing in the ear
4. Blurred or double vision
5. Nausea and vomiting
6. Dizziness, light-headedness, confusion, drowsiness
7. Breathlessness

Where is the study run from?
This study is being run by the Imperial College London and takes place in two NHS hospitals in England (UK)

When is the study starting, and how long is it expected to run for?
October 2020 to August 2024

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Raha West
flicor.trial@imperial.ac.uk

Contact information

Dr Raha West
Principal investigator

369 Fulham Road
London
SW10 9NH
United Kingdom

ORCID ID	0000-0003-1338-0252
Phone	+44 (0)7496833117
Email	flicor.trial@imperial.ac.uk

Dr Keith Boland
Scientific

St Marys Campus
Room 221
Level 2
Medical School Building
Norfolk Place
London
W2 1PG
United Kingdom

Phone	+44 (0)207 594 9480
Email	k.boland@imperial.ac.uk

Study information

Primary study design	Interventional
Study design	Randomized controlled double-blind parallel-group trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised feasibility study evaluating the effect of perioperative intravenous lIdocaine on colorectal cancer outcome after surgery
Study acronym	FLICOR
Study objectives	There are strong pre-clinical evidence to suggest that lidocaine, a type of local anaesthetic which is commonly used, could potentially reduce cancer recurrence if given during cancer surgery. This study aims to assess the feasibility of conducting a study comparing intravenous lidocaine infusion versus placebo administration for 24 hours, from the start of general anaesthesia. The specific population will be any stage 2 or 3, colon or rectal cancer patient undergoing elective laparoscopic colorectal cancer surgery to look at postoperative cancer outcomes in the NHS setting. This study will explore the acceptability, facilitators and potential barriers of recruiting cancer patients, with possible anxieties of a new cancer diagnosis about to have major surgery along with other potential feasibility issues. It will also assess if follow-up and outcome data collection can be streamlined with usual care processes as much as possible and to guide the future definitive trial. 1. To collect data on clinical and patient-reported outcomes at 6 and 12 months to inform the definitive trial. This includes cancer recurrence and death from any cause, colorectal cancer-specific quality of life questionnaire and total hospital stay at 12 months. 2. Exploratory outcome to look at the potential clinically relevant mechanism of lidocaine from blood tests during treatment that may suggest how lidocaine could reduce cancer recurrence. Measurement from the blood will include circulating tumour cells (CTCs) quantity (this is not detectable by the conventional test that is usually used for cancer surveillance), a potential by product of cancer cells breakdown called circulating free DNA (cfDNA) and pro-inflammatory cytokines (these are biomarkers released by the body in response to surgery and can influence cancer recurrence). We will also see if these may be suitable markers and if it would be feasible to undertake this work as part of the future definitive trial.
Ethics approval(s)	Approved 15/03/2022, London - Dulwich Research Ethics Committee (Health Research Authority, 2nd Floor, 2 Redman Place, Stratford, London, E20 1JO, UK; +44 (0)207 104 8241; dulwich.rec@hra.nhs.uk), ref: 22/LO/0114
Health condition(s) or problem(s) studied	Colorectal cancer patient undergoing surgery for cancer resection
Intervention	The feasibility trial will be a double-blinded, randomised, controlled trial, comparing intravenous lidocaine administration versus placebo. An intravenous bolus of 2% lidocaine or placebo will be administered following the induction of anaesthesia at 1.5 mg/kg ideal body weight over 20 minutes followed by intravenous infusion of 1.5 mg/kg/hour ideal body weight with a maximum rate of 120 mg/hour for 24 hours, in patients undergoing laparoscopic colorectal cancer surgery for stage 2 or stage 3, colon or rectal cancer. The randomisation method will involve a 1:1 parallel allocation ratio to either lidocaine or placebo. All patients will be followed up until 12 months from the date of study drug administration.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Lidocaine hydrochloride 2% for injection
Primary outcome measure(s)	Feasibility outcomes measured at baseline, hospital discharge, 6- and 12-months follow up post-randomisation: 1. The number of eligible patients and the actual number recruited for colon and rectal cancer with stage 2 or 3, taken from screening and recruitment logs 2. Trial retention measures by the number of participants who consent to participate who remain in the study until the end of follow up at 12 months 3. The feasibility, acceptability and return rates of data collection instruments, including those for the future economic evaluation alongside the definitive trial, measured using: 3.1. The completeness of responses to the health-related quality of life questionnaire, EQ- 5D-5L, collected at baseline, 6- and 12-months follow-up visit, which would be the outcome measure used in an economic evaluation as part of the definitive trial 3.2. The completeness of resource use data collected from an NHS and personal social services perspective using inpatient resource use data collected during the hospital stay from medical notes. A healthcare resource use form will be piloted for the definitive trial. This will be a bespoke patient questionnaire on primary and secondary healthcare and social care resource use following discharge at 6- and 12-months telephone follow up 4. Participants and clinical staff's experiences of the research process will be assessed at the end of the study with a short (10-question) close-ended questionnaire with optional free text relating to informed consent procedures, the information given, the recruitment process and any suggestions for improvement 5. Patients who refuse consent will be asked for their reasons at the point of recruitment only. Clinicians will be asked their reasons for not recruiting patients. Responses will be recorded on the screening log.
Key secondary outcome measure(s)	Clinical and patient-reported outcomes: 1. Disease-free survival, including cancer recurrence and death from any cause, will be captured from hospital medical records, health care resource use form and GP records at 12 months post-randomisation. Cancer recurrence will be assessed from routine cancer surveillance, including CT scan, colonoscopy, serum carcinoembryonic antigen tests, and histopathology reports. The cause of death will be looked at from the hospital and GP records. 2. Feasibility and completion of the outcome measure cancer-specific quality of life measured using the Functional Assessment of Cancer Therapy-Colorectal cancer (FACT-C) questionnaire at baseline, 6- and 12-months phone follow-up 3. Return to theatre, routine blood results, complications, blood transfusion and total hospital stay including readmission up to 12 months will be recorded from medical notes and healthcare resource use form Exploratory outcomes All measured at baseline, during surgery, at 24 hours (following completion of treatment) and on day 3: 1. The quantity of circulating free DNA in patients’ blood measured using circulating nucleic acid kit (Qiagen) and quantitative polymerase chain reaction assays and DNA next-generation sequencing panel for whole-genome sequencing on samples. 2. The circulating tumour cells quantity and functional characteristics between the two treatment groups will be measured using the cellular fraction of peripheral blood mononuclear cells through a sorter for non-immune cells. Cells will be cultured in vitro; functional characterisation study with flow method. 3. Pro-inflammatory cytokine levels measured using an enzyme-linked immunosorbent assay
Completion date	15/09/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	50
Key inclusion criteria	1. Aged 18 years and above, undergoing laparoscopic surgery with stage 2 or 3 colon cancer 2. Ability and willingness to consent
Key exclusion criteria	1. Stage 1 and stage 4 colon or rectal cancer 2. Palliative surgery with no curative intent 3. Extensive comorbidities, i.e. American Society of Anesthesiologists (ASA) Score IV 4. Patients with known allergy to lidocaine 5. Patients who are pregnant or breastfeeding 6. Patients who are likely to have adverse effects from the accumulation of intravenous lidocaine: 6.1. Known liver disease with liver function outside the normal laboratory range 6.2. Epilepsy 6.3. Cardiac conduction abnormalities based on history and confirmed by electrocardiogram
Date of first enrolment	15/09/2022
Date of final enrolment	30/06/2024

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Charing Cross Hospital

Fulham Palace Road
London
W6 8RF
United Kingdom

Chelsea & Westminster Hospital

369 Fulham Road
London
SW10 9NH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Participants will be informed and asked for their consent for the information collected about them to be used to support other research in the future, including that outside of the EEA. In line with the principles of research transparency, data may be shared with other researchers upon reasonable request. Before sharing, data will be anonymised so that the data subject is no longer identifiable. Data will be available upon reasonable request and approval by the sponsor, please contact Dr Raha West (flicor.trial@imperial.ac.uk). Data will be anonymised and available 1 year after the end of the study.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		30/06/2023	03/07/2023	Yes	No
HRA research summary			20/09/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

20/09/2023: A link to the HRA research summary was added.
03/07/2023: Publication reference added.
09/06/2023: The overall end date was changed from 30/08/2024 to 15/09/2024.
06/10/2022: The recruitment start date was changed from 22/08/2022 to 15/09/2022.
02/08/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 14/07/2022 to 22/08/2022.
2. The recruitment end date was changed from 31/10/2023 to 30/06/2024.
3. The overall trial end date was changed from 31/01/2024 to 30/08/2024.
4. The intention to publish date was changed from 31/10/2024 to 31/12/2024.
21/06/2022: The recruitment start date was changed from 13/06/2022 to 14/07/2022.
05/05/2022: Internal review.
06/04/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 05/04/2022.
21/01/2022: Trial's existence confirmed by the HRA.