Non-Small Cell Lung Cancer
Conditions
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.
Interventions
PROCEDUREBiopsy 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.
Sponsors
AstraZeneca
The Christie NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Suitability of pre and during radiotherapy biopsy for PD-L1 testing | Up to 6.5 weeks from start of radiotherapy |
Other
| 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 |
Countries
United Kingdom
Outcome results
None listed