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

Anthony Kong; Amanda J Kirkham; Joshua S Savage; Rhys Mant; Siân Lax; James Good; Martin D Forster; Joseph J Sacco; Stephano Schipani; Kevin J Harrington; Christina Yap; Hisham Mehanna

doi:10.1038/s44276-023-00026-6

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

BJC Rep. 2024;2(1):6. doi: 10.1038/s44276-023-00026-6. Epub 2024 Jan 29.

Authors

Affiliations

¹ King's College London, London, UK.
² Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, UK.
³ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁴ UCL Cancer Institute / University College London Hospitals NHS Foundation Trust, London, UK.
⁵ The Clatterbridge Cancer Centre, Wirral/University of Liverpool, Liverpool, UK.
⁶ Beatson West of Scotland Cancer Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁷ The Institute of Cancer Research, London, UK.
⁸ Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK.
⁹ InHANSE, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

^# Contributed equally.

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.

Clinical trial registration: ISRCTN76291951.