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Hypopharynx Squamous Cell CarcinomaPhase 1WISTERIANCT03028766

WEE1 Inhibitor with Cisplatin and Radiotherapy: a Trial in Head and Neck Cancer

A Phase 1 study testing AZD1775, Cisplatin and Radiotherapy in people with Hypopharynx Squamous Cell Carcinoma and Oral Cavity Squamous Cell Carcinoma, run by University of Birmingham at 6 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
AZD1775, Cisplatin and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
6 sitesUnited Kingdom
Study dates
22 Jun 2017to 3 Feb 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • Inclusion criteria Group A - in addition to general criteria
  • Accessible tumours for re-biopsy under local anaesthetic or via ultrasound guided biopsy
  • 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
  • Patients who have previously registered to Group A can be considered for inclusion in Group B

Who cannot join

  • 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
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  • 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)
  • Patients who have a history of Torsades de pointes (unless all risk factors that contributed to Torsades de pointes have been corrected)
  • Active gastro-intestinal disease that might limit absorption of study drug, e.g. coeliac disease, Crohn's disease, ulcerative colitis, pancreatic insufficiency
  • Evidence of any psychological, familial, sociological or geographical condition potentially hampering protocol compliance
  • Participation in another interventional clinical trial whilst taking part in this trial
  • 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
  • Clinical judgement by the Investigator that the patient should not participate in the study
  • Known hypersensitivity to the study drugs or active substances or excipients of the preparations
  • Pregnant or breast feeding patients
  • Significant pre-existing neuropathy which currently interferes with the patient's daily life
  • 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
  • Inability to swallow oral medications

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United Kingdom6 sites

  • University Hospital Birmingham Nhs Foundation Trust

    Birmingham, West Midlands, B15 2TH

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • St. James' University Hospital, Leeds Teaching Hospital NHS Trust

    Leeds, LS9 7TF

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • University College London Hospitals

    London, W1T 7HA

  • Clatterbridge Cancer Centre

    Metropolitan Borough of Wirral, CH63 4JY

Other trials in United Kingdom

About this study

Official 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

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.

Read the detailed description

Patients with head and neck cancer with high-risk features are at increased risk of relapse after surgery. Surgery, often followed by cisplatin chemotherapy and radiotherapy is currently the standard treatment offered. Whilst chemo-radiotherapy improves cure rates, outcomes remain poor, and treatment has a significant impact on quality of life. Chemotherapy has yet to find a definitive role prior to surgery. There is therefore an urgent need to develop more effective treatments which improve cure rates for this patient population.

The purpose of this trial is to see whether incorporating a drug called AZD1775 into the management of head and neck cancer offers the possibility of addressing these clinical issues. AZD1775 is a drug that has been shown to increase the effect of cisplatin and of radiotherapy when tested in the laboratory. The blood samples and tumour biopsies taken during the trial will be important in learning as much as possible about the effects of AZD1775 on the body and to investigate how the tumour might develop resistance to the drug.

The WISTERIA trial is for patients aged between 18 and 70 years with cancer of the oral cavity, larynx and hypopharynx who are to undergo surgery. Patients recruited to Group A must have accessible tumours for re-biopsy, whilst patients recruited to Group B will be at high risk of relapse after surgery.

The primary objective of this trial is to see what dose of AZD1775 can safely be given in combination with cisplatin before surgery (Group A) and with chemo-radiotherapy after surgery (Group B). The Investigators will also get some preliminary information regarding the effectiveness of this combined treatment. To find the safe and effective dose of AZD1775, different doses will be tested for each Group.

Being tested
AZD1775, Cisplatin, Radiotherapy
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Laryngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD1775Drug

    AZD1775 is a potent, selective small molecule inhibitor of WEE1

  • CisplatinDrug

    Chemotherapy drug

  • RadiotherapyRadiation

    Also called IMRT

    Intensity Modulated Radiotherapy

Study groups in NCT03028766
Study groupRoleWhat they receive
Group A - Pre-operativeExperimentalPatients 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.
Receives: Drug: AZD1775; Drug: Cisplatin
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.
Receives: Drug: AZD1775; Drug: Cisplatin; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Group A - Up to 42 days from start of treatment; Group B - Up to 12 weeks from the start of treatment

  2. 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.

    Measured: From registration, while on treatment and during follow up periods

Secondary outcomes (1)

  1. Disease-free survival in Groups A and B

    Disease-free survival is defined as the time from trial entry to date of disease recurrence, progression or patient death until end of follow up period.

    Measured: Patients will be followed-up clinically for 12 weeks in Group A and for 12 months in Group B.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2017 (estimated)
  2. Study start22 Jun 2017
  3. Primary completion31 Oct 2019
  4. Study completion3 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03028766
Sponsor's protocol ID
RG_15-139
Other IDs
2015-003583-37, ISRCTN76291951, 2015
Acronym
WISTERIA
Status last verified
Sep 2024
First submitted
4 Jan 2017
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 39220748

  • Kong 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.

    PubMed 32184305

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD1775, Cisplatin and Radiotherapy in people with Hypopharynx Squamous Cell Carcinoma and Oral Cavity Squamous Cell Carcinoma, run by University of Birmingham at 6 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended dose(s) of AZD1775 (time frame: Group A - Up to 42 days from start of treatment; Group B - Up to 12 weeks from the start of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03028766, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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