Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer.
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ICR Authors
Authors
Kong, A
Kirkham, AJ
Savage, JS
Mant, R
Lax, S
Good, J
Forster, MD
Sacco, JJ
Schipani, S
Harrington, KJ
Yap, C
Mehanna, H
Kirkham, AJ
Savage, JS
Mant, R
Lax, S
Good, J
Forster, MD
Sacco, JJ
Schipani, S
Harrington, KJ
Yap, C
Mehanna, H
Document Type
Journal Article
Date
2024-01-29
Date Accepted
2023-12-14
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.
Citation
BJC Reports,
DOI
Source Title
BJC Reports
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SPRINGERNATURE
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eISSN
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Research Team
Clin Trials & Stats Unit