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Wisteria

 

 

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

 

Summary:

The WISTERIA Trial is looking at using a new drug called AZD1775 before surgery and after surgery in patients with head and neck cancer. It is for people aged between 18 and 70 years old who have cancer of the oral cavity, larynx or hypopharynx and who are due to undergo surgery.

There are two groups in this trial. The first group (Group A) have AZD1775 and cisplatin before surgery. The second group (Group B) have radiotherapy, cisplatin and AZD1775 after 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 aims of this trial are to find the best dose of AZD1775 to have with cisplatin before surgery (Group A) and the best dose of AZD1775 to have with radiotherapy and cisplatin after surgery (Group B). We will also get some preliminary information regarding the effectiveness of this combined treatment.

 

Eligibility:

Inclusion criteria - all patients

  • 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:
  • 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.

 

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

 

Exclusion criteria – all patients

  • 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
  • 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 concurrently or within 4 weeks of starting this trial
  • Uncontrolled intercurrent illness which will interfere with the patient’s participation in the trial
  • 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 > once weekly)
  • Patients who have a history of Torsades de pointes (unless all risk factors that contributed to Torsades 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, including live vaccines, and unable to tolerate a washout period for at least 14 days prior to trial entry
  • Patients with any contraindications to cisplatin use (see cisplatin Summary of Product Characteristics)
  • 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

 

Status:

Open to recruitment

 

Lead Centre:

Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham

 

Study Coordinator

WISTERIA Trial Office

Cancer Research UK Clinical Trials Unit (CRCTU)

Institute of Cancer and Genomic Sciences

University of Birmingham

Edgbaston

Birmingham B15 2TT

 

Tel:   +44 (0)121 414 6788

Fax:  +44 (0)121 414 3529

 

Website:   Wisteria

Email:        wisteria@trials.bham.ac.uk


WISTERIA is a trial designed and co-ordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU).