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

Non-Small Cell Lung Cancer Clinical Trial

— PD-RAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03258788
• Other study ID #: CFTSp095, 14_DOG07_183
• Status: Completed
• Start date: January 3, 2019
• Est. completion date: March 18, 2020

Study information

• Verified date: March 2023
• Source: The Christie NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 18, 2020
• Est. primary completion date: March 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	St. James's Univerisity Hospital	Leeds
United Kingdom	University College Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust	AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in PD-L1 expression level during treatment		Up to 6.5 weeks from start of radiotherapy
Other	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
Other	Immune monitoring of primary tumour and peripheral blood mononuclear cells		Up to 6.5 weeks from start of radiotherapy
Primary	Achieving paired biopsies for PD-L1 assessment in 21 of the 30 evaluable participants		Up to 6.5 weeks from start of radiotherapy
Secondary	Suitability of pre and during radiotherapy biopsy for PD-L1 testing		Up to 6.5 weeks from start of radiotherapy

External Links

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