Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer

Kong, A. et al. (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2(1), 6. (doi: 10.1038/s44276-023-00026-6)

Abstract

Background Pre-clinical studies suggest AZD1775, a WEE1 kinase inhibitor, potentiates the activity of various chemotherapeutic agents. Methods WISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. Eligible patients had histologically confirmed oral, laryngeal, or hypopharyngeal squamous cell carcinoma, ECOG performance status 0/1, and aged ≥18-to-≤70 years. Primary outcomes were adverse events and defining recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative (Group A), or with cisplatin/radiotherapy in post-operative (Group B) patients. Dose determination was guided by a modified time-to-event continual reassessment method (mTITE-CRM). Results Between 30-Oct-2017 and 15-Jul-2019, nine patients were registered: Three into Group A and six into Group B. WISTERIA was closed early due to poor recruitment. Five dose-limiting toxicities (DLTs) were reported in four Group B patients. Seven serious adverse events were reported in four patients: One in Group A, and three in Group B. Three were related to treatment. No treatment-related deaths were reported. Conclusions WISTERIA did not complete its primary objectives due to poor recruitment and toxicities reported in Group B. However, use of the novel mTITE-CRM improved flexibility in reducing accrual suspension periods and should be considered for future trials in complex patient populations.

• Item Type: Articles
• Additional Information: This work was funded by Cancer Research UK [C19677/A20959] and AstraZeneca through Cancer Research UK’s Combinations Alliance. AZD1775 was provided free of charge by AstraZeneca. Staff at the CRCTU are supported by a core funding grant from Cancer Research UK [C22436/A25354]. WISTERIA was supported by Experimental Cancer Medicine Centres (ECMC) funding and by the ECMC Network. MDF is supported by the UCL/UCLH NIHR Biomedical Research Centre and runs early phase studies in the NIHR UCLH Clinical Research Facility, supported by the UCL ECMC.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Schipani, Dr Stefano
• Authors: Kong, A., Kirkham, A. J., Savage, J. S., Mant, R., Lax, S., Good, J., Forster, M. D., Sacco, J. J., Schipani, S., Harrington, K. J., Yap, C., and Mehanna, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BJC Reports
• Publisher: Springer Nature
• ISSN: 2731-9377
• ISSN (Online): 2731-9377
• Copyright Holders: Copyright: © The Author(s) 2024
• First Published: First published in BJC Reports 2(1): 6
• Publisher Policy: Reproduced under a Creative Commons licence