Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial.
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Embargo End Date
ICR Authors
Authors
Crabb, S
Wickens, R
Jane-Bibby, S
Dunkley, D
Lawrence, M
Knight, A
Jones, R
Birtle, A
Huddart, R
Linch, M
Martin, J
Coleman, A
Boukas, K
Markham, H
Griffiths, G
Wickens, R
Jane-Bibby, S
Dunkley, D
Lawrence, M
Knight, A
Jones, R
Birtle, A
Huddart, R
Linch, M
Martin, J
Coleman, A
Boukas, K
Markham, H
Griffiths, G
Document Type
Journal Article
Date
2023-09-19
Date Accepted
2023-09-12
Abstract
BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATIONS: EudraCT Number: 2021-001995-32 (issued 8th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).
Citation
BMC Cancer, 2023, 23 (1), pp. 885 -
Source Title
BMC Cancer
Publisher
BMC
ISSN
1471-2407
eISSN
1471-2407
1471-2407
1471-2407
Collections
Research Team
Clinic Acad RT Huddart