Crabb, Simon, Wickens, Robin, Jane-Bibby, Sarah, Dunkley, Denise, Lawrence, Megan, Knight, Allen, Jones, Robert 
ORCID: 0000-0001-5608-001X, Birtle, Alison, Huddart, Robert, Linch, Mark et al (show 5 more authors)
(2023)
Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial.
BMC cancer, 23 (1).
p. 885.
Abstract
<h4>Background</h4>Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial.<h4>Methods</h4>AURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon's 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses.<h4>Discussion</h4>If this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients.<h4>Trial registrations</h4>EudraCT Number: 2021-001995-32 (issued 8<sup>th</sup> September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Urinary Tract, Humans, Carcinoma, Squamous Cell, Quality of Life, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Tumor Microenvironment, B7-H1 Antigen |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Jan 2024 10:10 |
| Last Modified: | 31 Jan 2024 10:11 |
| DOI: | 10.1186/s12885-023-11397-x |
| Open Access URL: | https://doi.org/10.1186/s12885-023-11397-x |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178159 |
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