A randomised feasibility study evaluating the effect of perioperative intravenous lidocaine on colorectal cancer outcome after surgery

BackgroundSurgery is the main curative treatment for colorectal cancer (CRC). Recurrence following surgical resection occurs in up to 50% of patients and is the leading cause of death. Cancer stage affects recurrence. Before surgery, a small number of clinically undetectable circulating cancer cells (CTCs) are often present.

Usually, the body can deal with these but the mechanism that occurs during surgery for wound healing changes this.

The effect of the surgical stress response on the immune system leads to the release of inflammatory 'soup', promoting the distribution of CTCs into the circulation leading to cancer recurrence and metastasis. Lidocaine is safe, affordable and available worldwide. In preclinical studies lidocaine cause CTC death and alleviate surgery's pro-metastatic inflammatory environments.

This evidence provides an exciting possibility that lidocaine could be repurposed as a drug to help prevent cancer metastases and substantiates the urgent need for a randomised control trial. Twelve patient and public involvement (PPI) representatives were involved with the study's development. Three PPI will remain throughout the study.

It was prioritised by the James Lind Alliance, a partnership between patients, carers and clinicians, and Bowel Cancer UK, a national charity organisation.

Research questions Is it feasible to conduct a study of intravenous lidocaine infusion versus placebo for 24 hours for CRC surgery to look at postoperative cancer outcomes in the NHS setting?

Can quantifying circulating free DNA (cfDNA), a by-product of CTCs lysis, provides an early signal of a clinically relevant mechanism of lidocaine and is this a possible outcome measure for the definitive trial?Objectives To assess the feasibility of: recruiting eligible patients for colon or rectal cancers (stages 2 or 3); lidocaine and placebo administration for 24 hours during and after surgery; retaining trial participants for 12 months; data collection instruments, including those for a future economic evaluation, clinical and patient-reported outcomes.

A preliminary look at cfDNA as an indicator of cancer cell lysis following lidocaine infusion and assess the feasibility of this work.MethodsThe feasibility study will be a double-blinded, randomised (1:1), controlled study, comparing intravenous lidocaine administration at 1.5mg/kg bolus followed by 1mg/kg infusion for 24 hours versus placebo, in patients undergoing laparoscopic CRC surgery.

Patients and clinicians will be asked to complete a feedback questionnaire on the study process. Blood will be collected upon the completion of lidocaine/placebo infusion for cfDNA. This will be processed to quantify cfDNA based on the recommended protocol. Timelines for delivery Recruitment is planned at two sites for 6 months.

There are screening, baseline and 6 total visits, including patients facing follow-up on day 3, 6 months and 12 months. Impact and disseminationThis feasibility study is set up to pave the way for a definitive trial.

The results will be presented at national and international conferences to stimulate interest and enthusiasm for centres to participate in the definitive trial. This research will also be published in academic journals. The PPI group will guide dissemination to patients and relevant charities.