A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer (PD-RAD)

A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer (NSCLC)

Participants with Non-Small Cell Lung Cancer (NSCLC), Performance Status (PS) 0-2, not suitable for concurrent Chemo-Radiotherapy (CTRT), will be treated with standard radiotherapy (radical or palliative). Archival tumour biopsies will be analysed for baseline Programmed Death Ligand 1 (PD-L1) expression. Some participants will have a biopsy before radiotherapy if the archive biopsy is not suitable. Participants will be required to undergo an additional mandatory biopsy of the irradiated site during the second week of radiotherapy.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Procedure: Biopsy and blood samples

Detailed Description

The purpose of this prospective, multicentre, non-randomised translational study is to provide proof of feasibility of achieving paired biopsies for PD-L1 assessment in patients with NSCLC treated with palliative or radical radiotherapy. This is a non-CTIMP study.

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

Participants will have up to a maximum of 2 additional optional biopsies (during radiotherapy [within the RT field e.g supraclavicular fossa node], [outside RT field e.g. skin met]).

Blood samples will also be taken on study at specified time points for immune monitoring (exploratory endpoints).

The study will be carried out in two stages as follows:

Stage 1:

Following the enrolment of the first 15 evaluable participants, an interim analysis will take place by the Trial Steering Committee (TSC). The TSC will make a recommendation on whether recruitment should continue to the Trial Management Group (TMG).

Stage 2:

A further 15 evaluable participants will be recruited onto the study to achieve a total of 30 evaluable participants.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St. James's Univerisity Hospital
  • London, United Kingdom, NW1 2BU
    • University College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Hospital clinic

Description

Inclusion Criteria:

• Histologically confirmed NSCLC
• Diagnostic/pre-treatment biopsy suitable for PD-L1 analysis*
• Tumour judged inoperable by a lung MDT
• Tumour that is accessible to core biopsy
• Age 18 and over, no upper age limit
• Performance status (PS) - ECOG 0-2
• Participant considered suitable for radiotherapy (palliative or radical) or sequential chemo-radiotherapy

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

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

    • have been formalin fixed for >12h and ≤24h
    • have tumour tissue and morphology confirmed by H&E staining
    • contain sufficient tumour cells (>100) to determine PD-L1 status

Exclusion Criteria:

• Participant suitable for standard concurrent CTRT
• Participant deemed unsuitable for repeat biopsies in the opinion of the treating oncologist
• Participant known to have an EGFR mutation or an ALK rearrangement
• Intercurrent or history of hepatitis B, C or human immunodeficiency virus infection, if known
• Participants who have received more than 1 line of chemotherapy prior to radiotherapy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Non-Small Cell Lung Cancer; Participants with NSCLC not suitable for concurrent CTRT, being treated with standard radiotherapy (radical or palliative). All participants will be required to undergo a post radiotherapy course biopsy and will have blood samples taken.

Procedure: Biopsy and blood samples; Archival tumour biopsies will be analysed for baseline PD-L1 expression. Some participants will have a biopsy before radiotherapy if the archival biopsy is not suitable. Participants will be required to undergo an additional mandatory biopsy of the irradiated site during the second week. Patients must have completed at least 1 week of the planned treatment before taking the biopsy. Participants will also be asked for consent to donate 50ml blood pre biopsy (at baseline and week 2) and at the end of radiotherapy; as well as 10ml blood before #2 radiotherapy and weekly throughout treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Achieving paired biopsies for PD-L1 assessment in 21 of the 30 evaluable participants	Up to 6.5 weeks from start of radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Suitability of pre and during radiotherapy biopsy for PD-L1 testing	Up to 6.5 weeks from start of radiotherapy

Other Outcome Measures

Outcome Measure	Time Frame
Change in PD-L1 expression level during treatment	Up to 6.5 weeks from start of radiotherapy
Difference in PD-L1 expression level in 'out of radiotherapy field' sites compared with irradiated sites	Up to 6.5 weeks from start of radiotherapy
Immune monitoring of primary tumour and peripheral blood mononuclear cells	Up to 6.5 weeks from start of radiotherapy

Collaborators and Investigators

• Sponsor: The Christie NHS Foundation Trust
• Collaborators: AstraZeneca
• Investigators: Study Chair: Timothy Illidge, The Christie NHS Foundation Trust

Publications and helpful links

Helpful Links

• End of Trial Report - HRA
• University of Manchester - Website

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): March 18, 2020
• Study Completion (Actual): March 18, 2020

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CFTSp095, 14_DOG07_183

Drug and device information, study documents

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