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

Inclusion Criteria: * 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. 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 Exclusion Criteria: * 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) * 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