Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial.
Date
2023-09-19ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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).
Collections
Subject
Atezolizumab
Immunotherapy
PD-L1 expression
Phase II
Translational research
Urinary tract squamous cell carcinoma
Humans
B7-H1 Antigen
Quality of Life
Urinary Tract
Carcinoma, Squamous Cell
Tumor Microenvironment
Randomized Controlled Trials as Topic
Clinical Trials, Phase II as Topic
Multicenter Studies as Topic
Research team
Clinic Acad RT Huddart
Language
eng
Date accepted
2023-09-12
License start date
2023-09-19
Citation
BMC Cancer, 2023, 23 (1), pp. 885 -
Publisher
BMC