WISTERIA: WEE1 inhibitor with Cisplatin and Radiotherapy
Research type
Research Study
Full title
A Phase I trial of WEE1 inhibition with Chemotherapy and Radiotherapy as adjuvant treatment, and a Window of Opportunity trial with Cisplatin in Patients with Head and Neck Cancer
IRAS ID
185601
Contact name
Birgit Whitman
Contact email
Sponsor organisation
University of Birmingham
Eudract number
2015-003583-37
Duration of Study in the UK
2 years, 10 months, 1 days
Research summary
Research Summary
Head and neck cancer is the sixth most common cancer worldwide. Post-operative chemo-radiation is currently the best treatment offered for this type and stage of cancer. However, patients with certain histopathological features after surgery are at increased risk of local recurrence and death. Whilst chemo-radiation improves cure rates, three-year overall survival remains sub-optimal and treatment has a significant impact on quality of life for these patients.
WISTERIA is an open-label, phase I dose-finding, multicentre, clinical trial to determine the maximum tolerated dose (MTD) of AZD1775 in combination with post-operative cisplatin-based chemo-radiation; and a window of opportunity trial to determine the highest safe dose with pre-operative cisplatin chemotherapy, in patients with Head and Neck Cancer. The main purpose of the study is to determine how effective and safe it is to combine AZD1775 with cisplatin in the pre-operative setting (Group A) and with post-operative cisplatin based chemo-radiation (Group B) in patients with head and neck cancer. Only patients with histologically confirmed diagnosis of head and neck cancer of the oral cavity, larynx or hypopharynx who are planned to undergo surgery will be eligible for the trial. We wish to see whether combining AZD1775 with weekly cisplatin can reduce the need for post-operative chemo-radiation and lead towards treatment intensification for those with a particularly poor prognosis. We will do this by using blood tests and tissue samples at various time points to see if the trial drug is working. This will help us to determine whether AZD1775 warrants further investigation in patients in a phase II study.
The trial is funded by Cancer Research UK and AstraZeneca who will be providing the trial drug free of charge. Up to 42 patients will be recruited to Group A (21 patients) or B (21 patients) and is expected to last for approximately 4 years.
Summary of research
In the WISTERIA clinical trial (ISRCTN76291951), head and neck cancer patients were treated with a new drug, AZD1775 in addition to standard chemotherapy (cisplatin), either before or after surgery to remove their tumour. AZD1775 inhibits WEE1, a protein involved in the regulation of cell replication. This trial was trying to determine the most effective and safe dose of AZD1775 to give to patients. Patients were treated in groups of three, known as cohorts, and then assessed by an independent Trial Safety Committee (TSC) to decide if the dose can safely be increased, should remain the same or be reduced. This decision was based on the number of Dose Limiting Toxicities (DLTs) that were reported; DLTs are side effects or adverse events (AEs) that are specifically defined as significant in the trial protocol.
REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
16/WM/0501
Date of REC Opinion
22 Dec 2016
REC opinion
Favourable Opinion