Clinical trial NCT03258788: A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer
Official title: A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer (NSCLC)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2017-08-23
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospital clinic

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Achieving paired biopsies for PD-L1 assessment in 21 of the 30 evaluable participants
timeFrame: Up to 6.5 weeks from start of radiotherapy
Secondary outcomes:
measure: Suitability of pre and during radiotherapy biopsy for PD-L1 testing
timeFrame: Up to 6.5 weeks from start of radiotherapy
Other outcomes:
measure: Change in PD-L1 expression level during treatment
timeFrame: Up to 6.5 weeks from start of radiotherapy
measure: Difference in PD-L1 expression level in 'out of radiotherapy field' sites compared with irradiated sites
timeFrame: Up to 6.5 weeks from start of radiotherapy
measure: Immune monitoring of primary tumour and peripheral blood mononuclear cells
timeFrame: Up to 6.5 weeks from start of radiotherapy
Locations:
city: Leeds
country: United Kingdom
facility: St. James's Univerisity Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Timothy Illidge
role: STUDY_CHAIR
References: