WEE1 Inhibitor with Cisplatin and Radiotherapy: a Trial in Head and Neck Cancer
WISTERIA
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
3 other identifiers
interventional
9
1 country
6
Brief Summary
This trial is to determine what dose of a drug called AZD1775 can safely be given in combination with cisplatin before surgery and with chemo-radiotherapy after surgery in patients with Head and Neck Cancer. The Investigators will also get some preliminary information regarding the effectiveness of this combined treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2017
Typical duration for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 4, 2017
CompletedFirst Posted
Study publicly available on registry
January 23, 2017
CompletedStudy Start
First participant enrolled
June 22, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 3, 2021
CompletedSeptember 19, 2024
September 1, 2024
2.4 years
January 4, 2017
September 3, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Recommended dose(s) of AZD1775
Group A: The highest safe dose of AZD1775 in combination with cisplatin with a predefined target Dose Limiting Toxicity probability of 25% for up to 42 days from start of treatment. Group B: The maximum tolerated dose of AZD1775 in combination with cisplatin/radiotherapy with a target DLT of 30% for up to 12 weeks from the start of treatment.
Group A - Up to 42 days from start of treatment; Group B - Up to 12 weeks from the start of treatment
Safety profile of AZD1775 for Group A and Group B by reporting of all Adverse Events, Serious Adverse Events, Suspected Unexpected Adverse Reactions, deaths, deviations and withdrawal as assessed by the Safety Committee.
Safety profile of AZD1775 in combination with cisplatin in Group A and cisplatin/radiotherapy in Group B.
From registration, while on treatment and during follow up periods
Secondary Outcomes (1)
Disease-free survival in Groups A and B
Patients will be followed-up clinically for 12 weeks in Group A and for 12 months in Group B.
Study Arms (2)
Group A - Pre-operative
EXPERIMENTALPatients will receive the cohort specified dose of AZD1775 by mouth, twice a day for 3 days, commencing on days 1 and 8. Cisplatin 40mg/m2 IV delivered over 1 hour on day 8. Patients in this group will commence surgery within 42 days of commencing pre-operative chemotherapy.
Group B - Post-operative:
EXPERIMENTALPatients will received the cohort specified dose of AZD1775 by mouth, twice a day for 3 days on days 2, 9, 23 and 30. Cisplatin 40mg/m2 IV delivered over 1 hour on days 2, 9, 16, 23 and 30. Intensity Modulated Radiotherapy will be delivered 5 days a week (once daily, Monday to Friday) for 6 weeks commencing within 3 months of surgery.
Interventions
AZD1775 is a potent, selective small molecule inhibitor of WEE1
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of oral, laryngeal or hypopharyngeal squamous cell carcinoma
- Multi-Disciplinary Team (MDT) recommendation for surgical resection with curative intent
- Eastern Cooperative Oncology Group (ECOG) performance status 0/1
- Age ≥18 to ≤70 years
- Creatinine clearance, measured by Glomerular Filtration Rate (GFR), ≥ 60 ml/min at baseline calculated using local practice calculation. If this is ≤ 60 ml/min then an isotopic GFR may be carried out and must be \> 60 ml/min
- Acceptable cardiac function. If significant cardiac history, then required for patient to have Left Ventricular Ejection Fraction (LVEF) ≥55% by echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA, if ECHO is equivocal)
- Normal liver and bone marrow function:
- Haemoglobin (Hb) ≥10.0 g/dL or ≥100 g/L
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Absolute platelet count ≥100 x 109/L
- Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≤2.5 upper limit of normal (ULN)
- Total bilirubin ≤1.5 ULN (except for patients with known Gilbert's syndrome)
- Male and female participants must agree to take appropriate measures to prevent pregnancy. Contraceptive measures should be used for 2 weeks prior to trial entry, during the trial and for at least 6 months after last receiving treatment. Acceptable methods of contraception include total abstinence (if this is the patient's usual and preferred lifestyle choice), tubal ligation, combined oral, transdermal or intra-vaginal hormonal contraceptives, medroxyprogesterone injections (e.g. Depo-Provera), copper-banded intra-uterine devices; hormone impregnated intra-uterine systems and vasectomised partners. All methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by their male sexual partner for intercourse.
- Accessible tumours for re-biopsy under local anaesthetic or via ultrasound guided biopsy
- High-risk histopathological features after surgical resection, i.e. nodal extra-capsular spread and/or tissue resection margin \<1 mm as agreed at MDT
You may not qualify if:
- Any previous treatment for the same cancer, or previous head and neck malignancy, apart from laser excision of carcinoma in situ, with minimal residual functional deficit or registration and treatment in Group A prior to surgery
- Patients with cancer of the oropharynx or non-primary cancer will not be included
- Any metastatic disease from any primary site
- Use of an Investigational Medicinal Product (IMP) concurrently or within 4 weeks of starting this trial
- Uncontrolled intercurrent illness, which will interfere with the patient's participation in the trial, e.g.:
- myocardial infarction within 6 months
- congestive cardiac failure
- unstable angina
- symptomatic cardiomyopathy
- chronic infections
- active peptic ulcer or liver disease
- serious psychiatric condition limiting ability to comply with trial protocol
- Clinical evidence of current heart failure (≥New York Heart Association (NYHA) Class II)
- Clinical evidence of atrial fibrillation (with heart rate \>100 bpm, within 6 months prior to trial entry)
- Unstable ischaemic heart disease (Myocardial Infarction within 6 months prior to trial entry or angina requiring the use of nitrates greater than once weekly)
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Birminghamlead
- AstraZenecacollaborator
- Cancer Research UKcollaborator
Study Sites (6)
University Hospital Birmingham Nhs Foundation Trust
Birmingham, West Midlands, B15 2TH, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
St. James' University Hospital, Leeds Teaching Hospital NHS Trust
Leeds, LS9 7TF, United Kingdom
The Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
University College London Hospitals
London, W1T 7HA, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Related Publications (2)
Kong A, Kirkham AJ, Savage JS, Mant R, Lax S, Good J, Forster MD, Sacco JJ, Schipani S, Harrington KJ, Yap C, Mehanna H. 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.
PMID: 39220748BACKGROUNDKong A, Good J, Kirkham A, Savage J, Mant R, Llewellyn L, Parish J, Spruce R, Forster M, Schipani S, Harrington K, Sacco J, Murray P, Middleton G, Yap C, Mehanna H. 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: the WISTERIA trial protocol. BMJ Open. 2020 Mar 16;10(3):e033009. doi: 10.1136/bmjopen-2019-033009.
PMID: 32184305BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hisham Mehanna
University of Birmingham
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 4, 2017
First Posted
January 23, 2017
Study Start
June 22, 2017
Primary Completion
October 31, 2019
Study Completion
February 3, 2021
Last Updated
September 19, 2024
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- Data will be available within 6 months of the primary publication.
- Access Criteria
- See Plan Description above.
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. The CRCTU is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of trial participants. Data anonymised in compliance with the Information Commissioners Office requirements, using a procedure based on guidelines from the MRC Methodology Hubs, will be available for sharing with researchers outside of the trials team within 6 months of the primary publication. More detailed information on the CRCTU's Data Sharing Policy and the mechanism for obtaining data can be found on the CRCTU website: https://www.birmingham.ac.uk/research/activity/mds/trials/crctu/index.aspx.