Condition category
Cancer
Date applied
20/02/2017
Date assigned
21/02/2017
Last edited
25/10/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

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

Specialty: Cancer, Primary sub-specialty: Head and Neck Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of lip, oral cavity and pharynx, Cancer/ Malignant neoplasms of thyroid and other endocrine glands

Intervention

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 measures

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

01/12/2019

Reason abandoned

Eligibility

Participant 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

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

31/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Birmingham
B15 2GW
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

Southampton University Hospital
Tremona Road
Southampton
SO16 6YD
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

31/12/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

25/10/2017: Internal review. 16/10/2017: Cancer Help UK lay summary link added to plain English summary field. 25/09/2017: Internal review. 15/09/2017: Internal review. 23/06/2017: The recruitment start date was changed from 01/07/2017 to 22/06/2017. 07/06/2017: The recruitment start date was changed from 01/04/2017 to 01/07/2017.