Exploratory Study of Clonal Evolution in Cancer for Patients Undergoing Transoral Robotic Surgery for Radiation Exposed Residual/reCurrent Tumours of the Upper Aerodigestive Tract (RECUT Plus)

RECUT PLUS: Exploratory Study of Clonal Evolution in Cancer for Patients Undergoing Transoral Robotic Surgery for Radiation Exposed Residual/reCurrent Tumours of the Upper Aerodigestive Tract

Radical radiotherapy for head and neck squamous cell cancer (HNSCC) can be administered to primary disease with curative intent. Residual disease, recurrence or further tumours may subsequently occur in this irradiated field. It is unknown whether these cancers reflect primary resistance or represent the evolution of resistance on treatment.

Understanding this could allow stratification of patients to more effective primary treatments, such as transoral robotic surgery, or help tailor systemic therapies for these cancers in previously irradiated fields.

RECUT+ is an exploratory molecular analysis study to assess the selective impact of radiation therapy on HNSCC.

Participants will be recruited from the Royal Marsden Hospital (RMH), Chelsea, a tertiary referral H&N cancer unit in London, UK, specialising in transoral robotic surgery.

Retrospective participants will be identified from previous Head and neck MDT lists at RMH.

Prospective participants will be screened for by the RECUT+ team during the weekly H&N MDT meetings at the Royal Marsden Hospital (RMH).

Blood/saliva samples will be collected pre operatively (prospective participants) and post operatively (retrospective and prospective participants) for germline and circulating tumour DNA analysis.

Biopsy samples from the original cancer and resected specimens from the post radiotherapy residual/recurrent/new primary disease will undergo molecular analysis to assess for any selective impact of radiotherapy on these further tumours.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Other: DNA Analysis

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: John C Hardman, MBChB; Phone Number: 442073528171; Email: johncharles.hardman@nhs.net
• Study Contact Backup: Name: Sejal Jain; Phone Number: 020 8661 3567; Email: sejal.jain@rmh.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden Hospital
    • Contact: Prof Vinidh Paleri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing transoral robotic surgery for radiation exposed residual/recurrent/new primary tumours of the upper aerodigestive tract.

Description

Inclusion criteria

• Aged over 18
• Previous H&N cancer treated with radiotherapy.
• Undergoing TORS as part of their management for residual, recurrent or new primary H&N cancer.

Exclusion criteria

• Where TORS is used in a diagnostic setting only
• Nasopharyngeal and thyroid head and neck cancers
• Where no tissue specimens are available from the recurrent/residual/secondary tumour for the retrospective cohort

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective Cohort; Patients who have previously had radiotherapy and then have had their local residual/recurrent disease managed with salvage TORS at the Royal Marsden Hospital will be eligible for inclusion. They will be informed of the RECUT+ study by a member of their usual care team at RMH during their routine outpatient appointments for follow up of their H&N cancer. Potential participants will be asked to consent to provide blood/saliva sample for germline DNA and for permission for their original tumour biopsy sample and their residual/recurrent resection to undergo DNA analysis. Where patients have returned to their referring institution and are no longer under active regular follow up at RMH, a research pack will be sent to the patient via post and email. This pack will contain the Cover Letter, the Participant Information Sheet and the Informed Consent Form. It will also contain a saliva collection tube, buccal swab, blood tubes and instructions for how to provide blood/saliva samples.	Other: DNA Analysis; Molecular analysis includes DNA analysis on the blood/saliva and on the cancer specimens from the biopsies & subsequent resections
Prospective Cohort; Patients who have previously had radiotherapy and then are due to have their local residual/recurrent disease managed with salvage transoral robotic surgery at the Royal Marsden Hospital (RMH) will be approached prior to their salvage surgery at a routine outpatient appointment. They will be asked to consent to provide blood/saliva sample for germline DNA pre and post operatively. They will also be asked for permission for their original tumour biopsy sample and their residual/recurrent resection to undergo DNA analysis	Other: DNA Analysis; Molecular analysis includes DNA analysis on the blood/saliva and on the cancer specimens from the biopsies & subsequent resections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of resistant sub clones in post radiotherapy tumour samples	Identification of resistant sub clones in post radiotherapy tumour samples	Within 1 year of surgery & receipt of blood/saliva and tissue samples

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of differences in sub clonal architecture of H&N SCC before and after radiotherapy.	Identification of differences in sub clonal architecture of H&N SCC before and after radiotherapy.	Within 1 year of surgery & receipt of blood/saliva and tissue samples
Identification of differences in mutational signatures between the primary disease and resistant sub clones.	Identification of differences in mutational signatures between the primary disease and resistant sub clones.	Within 1 year of surgery & receipt of blood/saliva and tissue samples
Identification of loss of heterozygosity at the HLA loci in resistant sub clones	Identification of loss of heterozygosity at the HLA loci in resistant sub clones	Within 1 year of surgery & receipt of blood/saliva and tissue samples
Disease-specific and overall survival at 5 years related to identified molecular characteristics.	Disease-specific and overall survival at 5 years related to identified molecular characteristics.	5 years following the date of surgery of the final participant recruited.

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: Oracle Cancer Trust; Biomedical Research Centre
• Investigators: Principal Investigator: Prof Vinidh Paleri, The Royal Marsden Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Estimated): October 7, 2026
• Study Completion (Estimated): October 7, 2026

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: CCR 5263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No