Contact information
Type
Public
Primary contact
Mr Rhys Mant
ORCID ID
Contact details
Early Drug Development Team
CRUK Clinical Trials Unit
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 414 6788
wisteria@trials.bham.ac.uk
Additional identifiers
EudraCT number
2015-003583-37
ClinicalTrials.gov number
NCT03028766
Protocol/serial number
32918
Study information
Scientific 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
Acronym
WISTERIA
Study hypothesis
The aim of this 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.
Ethics approval
West Midlands – Edgbaston REC, 18/01/2017, ref: 16/WM/0501
Study design
Non-randomised; Interventional; Design type: Treatment, Drug, Radiotherapy
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Head and neck cancer
Intervention
Current interventions as of 04/05/2018:
Patients who have been diagnosed with cancer of the oral cavity, larynx or hypopharynx and are due to undergo surgery will be allocated to Group A. Patients who have been diagnosed with cancer of the oral cavity, larynx or hypopharynx, have undergone surgery and will require radiotherapy afterwards due to being considered to be at risk of relapse after surgery will be allocated to Group B.
Group A: Patients will receive the cohort specified dose of AZD1775, twice a day for the first 3 days of each week for 2 weeks. Patients will receive cisplatin at the start of the second week of treatment. Patients in this group will commence surgery within 42 days of commencing pre-operative chemotherapy. Patients will be followed-up clinically for 3 months.
Group B: Patients will receive the cohort specified dose of AZD1775, twice a day for 3 days, on Weeks 1, 2, 4 and 5. Patients will receive cisplatin at the start of each week of treatment for 5 weeks. Intensity Modulated Radiotherapy will be delivered 5 days a week (once daily, Monday to Friday) for 6 weeks commencing within 3 months of surgery. Patients will be followed up clinically for 12 months.
Previous interventions:
Patients who have been diagnosed with cancer of the oral cavity, larynx or hypopharynx and are due to undergo surgery will be allocated to Group A. Patients who have been diagnosed with cancer of the oral cavity, larynx or hypopharynx, have undergone surgery and will require radiotherapy afterwards due to being considered to be at risk of relapse after surgery will be allocated to Group B.
Group A: Patients will receive the cohort specified dose of AZD1775, twice a day for the first 3 days of each week for 2 weeks. Patients will receive cisplatin at the start of the second week of treatment. Patients in this group will commence surgery within 42 days of commencing pre-operative chemotherapy. Patients will be followed-up clinically for 3 months.
Group B: Patients will receive the cohort specified dose of AZD1775, twice a day for 3 days, for 5 weeks. Patients will receive cisplatin at the start of each week of treatment for 5 weeks. Intensity Modulated Radiotherapy will be delivered 5 days a week (once daily, Monday to Friday) for 6 weeks commencing within 42 days of surgery. Patients will be followed up clinically for 12 months.
Intervention type
Other
Phase
Phase I
Drug names
Primary outcome measure
1. Recommended dose(s) of AZD1775. For Group A this is measured as 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. For Group B this is measured as 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.
2. Safety profile of AZD1775 for Group A and Group B is assessed by reporting of all adverse events, serious adverse events, suspected unexpected adverse reactions, deaths, deviations and withdrawal as assessed by the Safety Committee from registration, while on treatment and during follow up periods
Secondary outcome measures
Disease-free survival is measured as the time from trial entry to date of disease recurrence, progression or patient death until end of follow up period
Overall trial start date
01/09/2015
Overall trial end date
29/01/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 04/05/2018:
1. Histologically confirmed diagnosis of oral, laryngeal or hypopharyngeal squamous cell carcinoma
2. Multi-Disciplinary Team (MDT) recommendation for surgical resection with curative intent
3. Eastern Cooperative Oncology Group (ECOG) performance status 0/1
4. Aged between 18 and 70 years
5. 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
6. 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)
7. Normal liver and bone marrow function:
7.1. Haemoglobin (Hb) > = 10.0 g/dL or > = 100 g/L
7.2. Absolute neutrophil count (ANC) > = 1.5 x 109/L
7.3. Absolute platelet count > = 100 x 109/L
7.4. Aspartate transaminase (AST) or alanine aminotransferase (ALT) < = 2.5 upper limit of normal (ULN)
7.5. Total bilirubin < = 1.5 ULN (except for patients with known Gilbert’s syndrome)
8. 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.
9. Inclusion criteria Group A – in addition to general criteria:
Accessible tumours for re-biopsy under local anaesthetic or via ultrasound guided biopsy
10. Inclusion criteria Group B – in addition to general criteria:
10.1. High-risk histopathological features after surgical resection, i.e. nodal extra-capsular spread and/or tissue resection margin <1 mm as agreed at MDT
10.2. Patients who have previously registered to Group A can be considered for inclusion in Group B
Previous inclusion criteria:
1. Histologically confirmed diagnosis of oral, laryngeal or hypopharyngeal squamous cell carcinoma
2. Multi-Disciplinary Team (MDT) recommendation for surgical resection with curative intent
3. Eastern Cooperative Oncology Group (ECOG) performance status 0/1
4. Aged between 18 and 70 years
5. 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
6. 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)
7. Normal liver and bone marrow function:
7.1. Haemoglobin (Hb) > = 10.0 g/dL or > = 100 g/L
7.2. Absolute neutrophil count (ANC) > = 1.5 x 109/L
7.3. Absolute platelet count > = 100 x 109/L
7.4. Aspartate transaminase (AST) or alanine aminotransferase (ALT) < = 2.5 upper limit of normal (ULN)
7.5. Total bilirubin < = 1.5 ULN (except for patients with known Gilbert’s syndrome)
8. 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.
Inclusion criteria Group A – in addition to general criteria:
Accessible tumours for re-biopsy under local anaesthetic, e.g. oral cancer
Inclusion criteria Group B – in addition to general criteria:
High-risk histopathological features after surgical resection, i.e. nodal extra-capsular spread and/or tissue resection margin < 1 mm as agreed at MDT
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 42; UK Sample Size: 42
Total final enrolment
9
Participant exclusion criteria
1. 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
2. Patients with cancer of the oropharynx will not be included
3. Any metastatic disease from any primary site
4. Use of an Investigational Medicinal Product concurrently or within 4 weeks of starting this trial
5. Uncontrolled intercurrent illness, which will interfere with the patient’s participation in the trial, e.g.:
5.1. Myocardial infarction within 6 months
5.2. Congestive cardiac failure
5.3. Unstable angina
5.4. Symptomatic cardiomyopathy
5.5. Chronic infections
5.6. Active peptic ulcer or liver disease
5.7. Serious psychiatric condition limiting ability to comply with trial protocol
6. Clinical evidence of current heart failure (> = New York Heart Association (NYHA) Class II)
7. Clinical evidence of atrial fibrillation (with heart rate > 100 bpm, within 6 months prior to starting treatment)
8. Unstable ischaemic heart disease (Myocardial Infarction within 6 months prior to trial entry or angina requiring the use of nitrates greater than once weekly)
9. Active gastro-intestinal disease that might limit absorption of study drug, e.g. coeliac disease, Crohn’s disease, ulcerative colitis, pancreatic insufficiency
10. Evidence of any psychological, familial, sociological or geographical condition potentially hampering protocol compliance
11. Participation in another interventional clinical trial whilst taking part in this trial
12. Patients who are unable to discontinue any prohibited drug and unable to tolerate a washout period for at least 14 days prior to trial entry
13. Clinical judgement by the Investigator that the patient should not participate in the study
14. Known hypersensitivity to the study drugs or active substances or excipients of the preparations
15. Pregnant or lactating patients
16. Significant pre-existing neuropathy which currently interferes with the patient’s daily life
17. Mean resting corrected QTc interval using the Fridericia formula (QTcF) > 450 msec (male) and > 470 msec (female) (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
18. Inability to swallow oral medications
Recruitment start date
22/06/2017
Recruitment end date
31/10/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom
Trial participating centre
University College London Hospital
235 Euston Road
London
NW1 2PG
United Kingdom
Trial participating centre
Clatterbridge Cancer Centre
Clatterbridge Road
Wirral
CH63 4JY
United Kingdom
Trial participating centre
Beatson West of Scotland Cancer
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 414 6788
wisteria@trials.bham.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
29/01/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list