Developing Circulating and Imaging Biomarkers Towards Personalised Radiotherapy in Lung Cancer (VIGILANCE)

In stage 3 NSCLC, treatment and follow-up are generally performed in a 'one-size-fits-all' manner. In the setting of metastatic lung cancer there has been considerable success identifying biomarkers, which allow treatments to be tailored and lead to more personalised medicine. In patients with stage 3 disease there exists a significant unmet clinical need for equivalent biomarkers to guide treatment decisions such as to identify poor responders, predict benefit from treatment and diagnose relapse before standard of care imaging. Recent advances have made it possible to detect and quantify circulating-tumour DNA in peripheral blood of patients with stage 3 NSCLC, a promising prognostic biomarker and a measure of minimal residual disease. In addition, the information contained in routine medical images and electronic patient reported outcome measure (ePROM) questionnaires can add further predictive power to circulating tumour DNA and other clinical factors to determine patient's outcome. There is scope to integrate biomarkers in treatment decision algorithms aiming to make personalised treatment modifications (e.g. decision to treat with immunotherapy or not). VIGILANCE is a highly exploratory observational study to understand how these biomarkers might inform a future hypothesis driven interventional study.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer Stage III

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Recruiting
    • The Christie NHS Foundation Trust
    • Principal Investigator: Corinne Faivre-Finn
    • Contact: Ashley Horne; Phone Number: 0161 446 3000; Email: the-christie.vigilance.lungtrial@nhs.net
    • Contact: Clare Dempsey; Email: vigilance@manchester.ac.uk
    • Sub-Investigator: Ashley Horne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients treated under The Christie NHS Foundation Trust, Greater Manchester

Description

Inclusion criteria:

• Histological or cytologically confirmed NSCLC.
• Unsuitable for surgery due to tumour or patient factors.
• Stage 3 A, B or C (TNM version 8).
• Planned to receive radical radiotherapy OR sequential chemoradiotherapy OR concurrent chemoradiotherapy +/- consolidation immunotherapy.
• Predicted life expectancy >12 weeks.
• Ability to provide written informed consent.
• Willingness to comply with study procedures.

Exclusion criteria:

• Mixed non-small cell and small cell tumours.
• Adjuvant radiotherapy post-surgery.
• Participation in a study of an interventional study as part of lung cancer treatment.
• Recent/active malignant disease which might impact study results.
• Psychotic disorders/cognitive impairment.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients diagnosed with stage 3 NSCLC; Patients will receive standard of care curative-intent radiotherapy treatment as decided by their primary oncologist. This includes radical radiotherapy, sequential chemoradiotherapy and concurrent chemoradiotherapy +/- consolidation immunotherapy. No changes in treatment. Patients will have data collected at baseline, during radiotherapy and for one year following radiotherapy. This longitudinal collection will include blood for circulating-tumour DNA analysis, electronic PROMS and radiomic analysis of standard of care imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prognostic model built using baseline and longitudinal circulating-tumour DNA, radiomic features and patient reported measures to predict survival, tumour control and early tumour relapse.	2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Longitudinal description of circulating-tumour DNA patterns at baseline, during and for up to 1 year following completion of radiotherapy.	2.5 years
Longitudinal description of radiomic features at baseline, during and for up to 1 year following completion of radiotherapy.	2.5 years
Longitudinal description of patient reported outcomes at baseline, during and for up to 1 year following completion of radiotherapy.	2.5 years
Predictive model built using baseline and longitudinal circulating-tumour DNA and radiomic features to predict benefit from consolidation immunotherapy.	2.5 years
Associations between features and changes in features over time will be described, e.g. radiomic features associated with circulating-tumour DNA and radiomic features.	2.5 years

Collaborators and Investigators

• Sponsor: University of Manchester
• Collaborators: Cancer Research UK

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Estimated): September 24, 2024
• Study Completion (Estimated): September 24, 2025

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 17, 2023

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; NSCLC; Radiotherapy; PROM; Non small cell lung cancer; Stage III; Radiomics; Circulating-tumour DNA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: NHS001986; 299279 (Other Identifier: IRAS ID); 22/NW/0297 (Other Identifier: REC number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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