Investigating the Tumour Immune Response of Radiotherapy (TIMM-RAD)

This study aims to investigate immune changes which occur before and following standard radiotherapy in a range of tumour types. We will collect tissue and blood samples before and after radiation treatment from participants across six cancer types: cervical, rectal, Head and Neck cancer, nodal non-Hodgkin lymphoma, cutaneous lymphoma and cutaneous squamous cell carcinoma/ basal cell carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Procedure: Biopsy and blood sample collection

Detailed Description

The purpose of this prospective, non-CTIMP, translational study is to assess the feasibility of achieving paired biopsies for immune analysis in patients across six different cancer types: cervical, rectal, Head and Neck cancer, nodal non-Hodgkin lymphoma, cutaneous lymphoma and cutaneous squamous cell carcinoma/ basal cell carcinoma.

All participants will have a minimum of 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) and the potential to have a pre-treatment biopsy if the archival biopsy does not meet the suitability criteria.

Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.

We aim to recruit 10-20 participants per study arm, with the option to increase numbers in study arms that are recruiting well - a maximum of 120 patients in total will be recruited to the study.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Lois Gardner; Phone Number: 01612008863; Email: lois.gardner@manchester.ac.uk
• Study Contact Backup: Name: Eleanor Cheadle; Phone Number: 01612008863; Email: eleanor.j.cheadle@manchester.ac.uk

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • Christie NHS Foundation Trust
    • Contact: Catherine Trigwell; Phone Number: 01613066088; Email: catherine.trigwell@manchester.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospital clinic

Description

Inclusion Criteria:

• Histologically confirmed cancer, Stage I-IV, in one of the following: Cervical, rectal, nodal Non-Hodgkin lymphoma, cutaneous lymphoma, Head & neck cancer
• Diagnostic/pre-treatment biopsy confirmed suitable for translational research *
• Performance status - ECOG 0-2 (Refer to appendix 1), ECOG 3 allowed for arm F (unrelated to underlying cancer) as this group of patients often have ECOG 3 due to age and comorbidities.
• Age ≥ 18; no upper age limit.
• Participant considered suitable for radiotherapy

• Before participant registration, written informed consent must be given according to GCP and national regulations.

  *Pre-treatment biopsy must be from the gross tumour volume within the planned radiation field and must also:

• Have been formalin fixed for >12h and <72h
• Have tumour tissue and morphology confirmed by H&E staining
• Contain sufficient tumour cells (approximately 100)

Exclusion Criteria:

• Participants deemed unsuitable for a biopsy (during or following radiotherapy) in the opinion of the treating oncologist.
• Participants who have received chemotherapy within 28 days of starting radiotherapy.
• Participants with intercurrent or past history of hepatitis B, C or human immunodeficiency virus infection if known. A negative test result for hepatitis B, C and HIV infection is required prior to inclusion in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cervical cancer; Cervical cancer patients receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.
Rectal cancer; Rectal cancer patients receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.
Head and neck cancer; Head and neck cancer patients receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.
nodal non-Hodgkin lymphoma; Patients with nodal NHL receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.
cutaneous lymphoma; Patients with cutaneous lymphoma receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.
cutaneous squamous cell carcinoma and basal cell carcinoma; Patients with cSCC and cBCC receiving standard of care radiotherapy	Procedure: Biopsy and blood sample collection; A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of obtaining paired biopsy samples	To assess the feasibility of obtaining tumour samples pre-radiotherapy (diagnostic or fresh) and a second biopsy during or immediately after radiotherapy, or a surgical sample, from patients undergoing standard of care RT.	Within 6-7 weeks of starting radiotherapy
Collection of matched blood samples	To obtain additional matched blood samples pre-radiotherapy, during or post-radiotherapy, and at the end of radiotherapy for assessment of immune status of peripheral blood in comparison to the intratumoural microenvironment.	Within 6-7 weeks of starting radiotherapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemistry analysis of expression markers on tumour tissue	Immunohistochemistry (IHC) analysis of expression markers on tumours pre-radiotherapy and during/post radiotherapy	Within 6-7 weeks of starting radiotherapy
RNA evaluation of immune signatures	RNA evaluation of immune signatures in tumour tissue and blood pre-radiotherapy and during/post radiotherapy	Within 6-7 weeks of starting radiotherapy
Analysis of peripheral blood mononuclear cells	Assessment of changes in immune phenotypic markers	Within 6-7 weeks of starting radiotherapy
Analysis of plasma proteins, cytokines and chemokines	Analysis of plasma proteins, cytokines and chemokines as biomarkers of immune response	Within 6-7 weeks of starting radiotherapy

Collaborators and Investigators

• Sponsor: University of Manchester
• Collaborators: The Christie NHS Foundation Trust
• Investigators: Study Chair: Timothy M Illidge, University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): August 14, 2026

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: NHS001688; 21-XTEAM-13 (Other Identifier: Christie NHS Foundation Trust)

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
• product manufactured in and exported from the U.S.: No