Liverpool Head & Neck Centre

Clinical Trials


As one of our main missions is to enhance the quality and safety of patient care, we have developed a comprehensive trial program to test new ways of diagnosing and treating both common and rare head and neck diseases.

In addition, our translational research studies aim to further understand the biology around why and how head and neck cancers arise, helping us to develop new treatments. At LHNC, we run one of the largest head and neck clinical trial programs in Europe and patients who choose to participate in a trial with us may often receive some of the most advanced treatment plans available internationally.

If you are a referrer, patient, or centre interested in collaborating, please take a look through our database for eligible studies and we’ld be delighted to hear from you.

ACTivity as medicine In Oncology for Head and Neck study (ACTIOHN study)

Chief investigator: Professor Jo Patterson

Outline: What is the feasibility of implementing personalised, flexible, and collaborative exercise programmes for head and neck cancer (HaNC) survivors?

Background: Rates of HaNC have almost doubled in the last decade. Treatment is aggressive and often multi-modal, resulting in fundamental changes to physical fitness, musculoskeletal function, breathing, speech, swallowing and appearance. Survival rates have improved, with increasing numbers of survivors, living longer with chronic side-effects. Physical exercise has proven benefits in several cancer groups; reducing fatigue, low mood, treatment toxicities and mortality rates, although few studies include HaNC survivors. This group has multiple challenges, often being less physically active pre-diagnosis with high alcohol and tobacco consumption, many patients have considerable co-morbidities, low socio-economic status and poor health literacy. HaNC services are centralised, with many living long distances from treatment centres. Recent evidence demonstrated that personalised exercise programmes tailored to circumstances and preferences improved outcomes and adherence. Further work is indicated to increase engagement, improve delivery and implementation of physical exercise in HaNC survivors.

Aim: To investigate delivery of personalised, flexible, and collaborative exercise programmes in HaNC

For: Patiens (male or female) >18 years of age with a new diagnosis (or upto 8-weeks post treatment) of head and neck cancer, with a plan for curative treatment.

  • Study Design

    This single armed study will assess feasibility of personalised exercise programme for 70 patients diagnosed with HaNC, across two centres

    Intervention

    An 8-week exercise programme which has been successfully piloted with seven HaNC survivors. It includes i) needs analysis with personalised goals and exercise preferences ii) programme prescribed, guided and supported by a Cancer Exercise Specialist iii) flexibility to accommodate changes in symptom-burden, preferred exercise type and location iv) content adhering to physical exercise cancer guidelines v) personalised exit plan to promote maintenance.

    Outcomes

    Primary outcomes are uptake, adherence and compliance. Secondary outcomes are safety, cardiorespiratory fitness, strength, endurance, agility and balance. Patient-reported outcomes include a fatigue scale, activity levels and QoL.

    Exclusion

    Those intended for palliative care or classified as high-risk on an exercise risk stratification tool

AIR-RRP

Chief investigator: Dr Andrew Sims (Freeman Hospital, Newcastle upon Tyne, UK)

Outline: Airway Intervention Registry (AIR): a research database to capture safety and efficacy outcomes of balloon dilatation in the treatment of airway stenosis and any intervention in the treatment of respiratory papillomatosis

For: Patient (male or female) aged 0-18 years diagnosed with airway stenosis who are indicated for balloon dilatation treatment, or patients (male or female) of any age diagnosed with respiratory papillomatosis and are indicated for any interventional treatment

  • Phase of study

    N/A

    What is the study treatment?

    None – retrospective data and data for every clinic and surgery

    Patient Group

    Inclusion:
    Patient/parent/guardian written informed assent/consent 
    Patient/parent/guardian able to complete paper surveys of patient health

    Exclusion Criteria

    Patient/parent/guardian unable/unwilling to provide written informed assent/consent

BEST OF

Global Chief investigator: Professor Christopher Simon (Lausanne University Hospital, Vaud, Switzerland)

UK Chief investigators: Professor Mererid Evans (Velindre NHS Trust & Cardiff University, UK) & Professor Terry Jones (Liverpool Head & Neck Centre, UK)

Outline: Best of radiotherapy (IMRT) compared with Best of surgery (trans-oral surgery)

For: T1-T2, N0 histologically SCC of the oropharynx (base of tongue, lateral pharyngeal wall, tonsil, glossotonsillar sulcus).

  • Phase of study

    PHASE III

    Patient Group

    Inclusion

    • Histologically SCC of the oropharynx BOT, Lateral pharyngeal wall, tonsil, glossotonsillar sulcus

    • TNM stage T1-T2, N0 

    • Local MDT decision within 2wks of randomisation

    • Scans within 4wks of randomisation 

    • Patients considered fit for surgery and adjuvant treatment by the local MDT

    • ECOG <2

    • Tissue available for HPV

    • Aged 18 or over 

    • Written informed consent provided 


    Exclusion

    • Patient with bilateral tumour

    • Any previous tx chemo RTT or targeted therapy

    • Any active malignancy - <5yrs Except skin cervical, prostate

    • Extension of the cancer across the midline of the base of the tongue

    • Involvement of >50% of the SP by cancer requiring a reconstruction with a free flap

    • Cancer originating SP or posterior pharyngeal wall 

    • Pre-existing dysphagia

    How many Groups in study?

    2
    Radiotherapy vs TOLR

    Primary endpoint

    MDADI score

    Secondary outcome

    Survival status

    Follow up

    Year 1 – every 6 weeks
    Year 2 – every 3 months
    Year 3-5 – every 6 months

    Videofluoroscopy and water swallow test 

    Baseline before randomisation within 2 weeks
    4.5 months post randomisation
    12 month
    5 years

COMPARE

Chief investigator: Professor Hisham Mehanna (University of Birmingham, UK)

Outline: Comparing alternative treatment regimes for intermediate and high-risk oropharyngeal cancer

For: Oropharyngeal squamous cell carcinoma (base of tongue, tonsil or uvula), with a treatment recommendation for definitive concurrent chemoradiotherapy

(All OPC T4 or N3 (HPV-pos and HPV-neg) OR all HPV-neg OPC T1-T4, N1-N3 or T3-4, N0 OR HPV-pos OPC T1-T4 with N2b-N3 nodes AND who are smokers ≥ 10 pack years current or previous smoking history)

  • Phase of study

    III

    What is the study treatment?

    Induction durvalumab plus arm 1 and then adjuvant durvalumab

    Patient Group

    Inclusion

    1.      Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil (includes bilateral tumours) and uvula, with a Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy

    2.      All OPC T4 or N3 (HPV-pos and HPV-neg) OR all HPV-neg OPC T1-T4, N1-N3 or T3-4, N0 OR HPV-pos OPC T1-T4 with N2b-N3 nodes AND who are smokers ≥ 10 pack years current or previous smoking history

    3.       Minimum life expectancy of 3 months
    Page xiii Version 8.0b, 02 Jun 2020

    4.      Eastern Cooperative Oncology Group (ECOG) performance status 0-1

    5.      Body weight of >30kg

    6.      Adequate renal function, estimated glomerular filtration rate (eGFR) >50ml/min calculated using Cockcroft-Gault formula

    7.      Adequate bone marrow function (absolute neutrophil count (ANC) ≥1.5 x 109/L, haemoglobin ≥9.0g/dL and platelets ≥100 x 109/L)

    8.      Adequate liver function i.e. serum bilirubin ≤1.5 times the upper limit of normal (ULN), AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

    9.      Prothrombin time (PT) ≤1.5 x ULN or International Normalised Ratio (INR) ≤1. 5

    10.   No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN)

    11.   Aged 18-70

    12.   Written informed consent given for the trial

    13.  Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply:

    How many Groups in study?

    ARM 1 – control concomitant CRT 

    ARM 1 – control concomitant CRT 


    Control Arm:

    Arm 1: Concomitant cisplatin chemotherapy plus radiotherapy

    Concomitant chemoradiotherapy, 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70Gy in 35F +/- neck dissection as indicated by clinical and radiological assessment 3-months post treatment. This is the international gold standard.

    Treatment Arm: Induction durvalumab plus arm 1 and then adjuvant durvalumab

    One dose of induction durvalumab 1500mg by intravenous (IV) infusion followed by arm 1 within four weeks. Within one-two weeks after the completion of arm 1, durvalumab

    Primary endpoint

    OS at 2 years

    Secondary outcome

    Toxicity
    Disease free survival 
    QOL
    Cost 
    Surgical complications 
    Molecular markers
    Swallowing

    Follow up

    5 yrs

Finding My Way UK

Chief investigator: Professor Nick Hulbert-Williams (University of Chester, UK)

Outline: Adaptation and Replication Testing of the Benefits of Online Psychological Support for Cancer Survivors

For: Those diagnosed with cancer and treated with aim to cure in the past 6 months.

  • Phase of study

    N/A

    What is the study treatment?

    A six-week online programme of cancer-specific cognitive-behavioural therapy modules, plus one additional booster module

    Patient Group

    Inclusion 

    The subject must satisfy the following criteria for entry into the study:

    • Been diagnosed with cancer in the past six months

    • Have received anti-cancer treatment with curative intent

    • Aged 16 years or over

    • Sufficiently proficient in English to provide informed consent and use the online programme

    • Able to access the internet

    • Currently have (or willing to set up) an active email address

    Exclusion

    Patients will be excluded from the study if any of the following applies:

    • Severe comorbidity considered by the screening nurse to interfere with the individual’s ability to complete the requirements of the study or provide informed consent (e.g., intellectual disability or neurological impairment).

    How many Groups in study?

    2

    Primary Endpoint

    • To determine whether the UK-adapted Finding My Way programme reduces cancer-specific distress.

    Secondary outcome

    • To determine the effects of the UK-adapted Finding My Way programme on anxiety, depression, and general stress.

    • To determine the effects of the UK-adapted Finding My Way programme on quality of life.

    Treatment plan

    The Finding My Way programme includes 6 weeks of content, plus an additional booster module presented one month after initial treatment completion. Participants will continue to be able to access website content for an additional 4 months after the final participant has completed all study-related activities.

HoT (Hemithyroidectomy or Total Thyroidectomy for "low-risk" thyroid cancers)

Chief investigator: Professor Dae Kim (The Royal Marsden Hospital, UK)

Outline: To compare thyroid cancer recurrence, quality of life, surgical morbidities/effects, and cost-effectiveness between total thyroidectomy and hemithyroidectomy (HT) in a national cancer setting

For: T1b-T2 papillary or follicular thyroid cancer, either diagnosed after hemithyroidectomy, or after biopsy.

  • Phase of study

    PHASE III

    What is the study treatment?

    Hemithyroidectomy (HT) or Total Thyroidectomy (TT) for "low-risk" thyroid cancers

    Patient Group

    Inclusion criteria for Group 1 (HT performed prior to diagnosis):

    • Low-risk thyroid cancer as defined by the American Thyroid Association 2015 and 8thAJCC TNM staging criteria:

    • Aged 16 or over

    Papillary thyroid cancer:

    • pT1b-2 (≤4cm)irrespective of molecular genetic markers

    • R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local MDT)

    • cN0 or pN0, pNX & pN1a (≤5 foci, no extranodal spread)

    • Confined to thyroid or minimal extrathyroidal extension

    • No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT)

    • No angioinvasion

    • Encapsulated FVPTC with capsular invasion only

    • Micro-PTC (≤1cm)

      • multifocal

      • unifocal with pN1a (≤5 foci; no extranodal spread)

    Follicular thyroid cancer (FTC), including oncocytic or Hürthle cell carcinoma:

    • pT1b-2 (≤4cm)irrespective of molecular genetic markers

      • Minimally invasive, with capsular invasion +/-minimal (≤4 foci) vascular invasion

    • Confined to thyroid or minimal extrathyroidal extension

    Exclusion criteria for Group 1 (HT performed prior to diagnosis):

    • >4cm

    • unifocal pT1a (≤1cm) PTC or FTC (unless pN1a as above)

    • non-invasive encapsulated FVPTC

    • Anaplastic, poorly differentiated or medullary thyroid carcinoma

    • R2

    • gross extrathyroidal extension

    • pT4 or macroscopic tumour invasion of loco-regional tissues or structures

    • pN1a with >5 foci or extranodal spread

    • pN1b

    • M1

    • Aggressive PTC with any of the following features:

      • Widely invasive

      • Poorly differentiated

      • Anaplastic

      • predominance of Tall cell, Columnar cell, Hobnail, Diffuse sclerosing and other higher risk variants

    • FTC, including oncocytic or Hürthle cell cancer with any of the following features:

      • Minimally invasive with extensive vascular invasion (now called encapsulated angioinvasive) (>4 foci)

      • Widely invasive

      • Poorly differentiated

      • Anaplastic

    Inclusion criteria for Group 2 (DTC on cytology or after core biopsy with no prior surgery yet):

    • Aged 16 or over

    • ‘low risk’ differentiated thyroid cancer confirmed by cytology or core biopsy.

    • cT1b-2 irrespective of molecular genetic markers

    • cN0

    • Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC)

    Exclusion criteria for Group 2 (DTC on cytology or after core biopsy with no prior surgery yet):

    • M1

    How many Groups in study?

    Two groups of patients will be recruited via thyroid MDT meetings:

    Group 1:

    Patients that have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC. Patients will be randomised to:

    • surveillance only

    or

    • a second operation to remove the rest of the thyroid gland (two-stage TT).

    Group 2:

    Patients that have been diagnosed with ‘low risk’ DTC using cytology (Thy5) or core biopsy but no surgery performed yet. Patients will be randomised to:

    • HT

    or

    • TT (single stage)

    Primary endpoint

    Pilot phase: monthly patient accrual rates

    Main trial: 3 year recurrence rate

    Secondary outcome

    • 5 year recurrence rate

    • Risk of loco-regional recurrence

    • Anatomical site of recurrence

    • Number and type of additional investigations and procedures after 1st surgery

    • Surgical outcomes & complications (RLN & Calcium)

    • Requirement for hormone replacement therapy

    • Quality of life

    • Full cost-effective analysis

    • Biochemical recurrence (role of Thyroglobulin (Tg) & rising Tg levels after HT)

    Follow up

    Patients will be followed up 6 months after surgery and then annually for up to 6 ½ years.

    Other related research

    Sub-study conducted by UCL CTC to test the clinical utility of patients completing QoL forms on a web-based app (software) versus the traditional method of paper forms.

LARCH - The LARyngeal Cancer coHort

Chief investigator: David Hamilton (Newcastle University, UK)

Outline: To establish a disease database of laryngeal cancer patients

For: Patients with a new diagnosis of larynx cancer

  • Phase of study

    N/A

    What is the study treatment?

    N/A

    Study Objectives

    Primary objectives

    To establish a disease database of laryngeal cancer patients in order to:

    Assess the difference in quality of life, disease specific and overall survival between treatment modalities in early and advanced laryngeal cancer.

    Assess the impact of patient-derived clinical features and tumour factors on treatment outcome (oncological, laryngeal function, quality of life, swallow, voice) in early and advanced laryngeal cancer and use this to develop a risk prediction tool.

    Secondary objectives

    To establish consent processes to allow researchers to re-contact patients for data on long term outcome and survivorship.

    Using the data, establish an initial risk communication tool in the disease.

    To develop the pathway for routine tissue and radiological scan collection for future studies, mapped to outcome.

    Patient Groups

    There are 2 groups in this study

    Inclusion criteria

    Suspected but unconfirmed laryngeal cancer (Group 1)

    Confirmed new diagnosis of laryngeal cancer (Group 2)

    Age over 18

    Capacity to consent

    Ability to understand written and spoken English

    Exclusion criteria

    Recurrence or second head and neck primary cancer

Liverpool Experimental Cancer Medicine Centre (LECMC) Biomarker Discovery Programme

Chief investigator: Professor Richard Shaw (Liverpool Head & Neck Centre, UK)

Outline: Prospective Sample Collection of head and neck malignancy specimens

For: Presumptive or actual diagnosis of HNSCC or recognised oral premalignant conditions (OPML), including but not exhaustively OED, PVL, and those individuals who have been treated for these conditions in the past.

  • Phase of study

    N/A

    What is the study treatment?

    N/A

    Patient Group

    Inclusion Criteria 
    Presumptive or actual diagnosis of HNSCC or recognised oral premalignant conditions (OPML), including but not exhaustively OED, PVL, and those individuals who have been treated for these conditions in the past. 

    Exclusion Criteria 
    Unable to consent , age under 18 or unable to read or translate patient information sheet and/or consent form.

    How many Groups in study?

    N/A

    Study objectives 

    With this Protocol the LECMC seeks to support current and future projects which: 

    • Investigate (comprising both discovery and validation) potential markers for: 

    - Outcomes after surgery 
    - Response to therapy, including toxicity Early diagnosis 
    - Test feasibility of biomarker analysis to specified time points 

    • Determine cut-off points and definitions for biomarker analysis 

    These biomarkers may be from a variety of sources (tissue, blood, saliva, urine, etc.) and be in a variety of forms. Research towards these goals will potentially allow for development of personalised treatment regimes, stratification of

    Treatment plan

    N/A

Mapping the genetic and epigenetic landscape of sinonasal carcinoma

Chief investigator: Dr. Manas Dave (University of Manchester, UK)

Outline: A multi-centre retrospective review of sinonasal malignancies from archived FFPE tissue

For: Tissue banked sinonasal malignancy specimens (2016-2019)

  • Phase of study

    N/A

    What is the study treatment?

    ARMS

    N/A

    Patient Group

    Inclusion 

    A review of all histopathology patient records at Manchester Royal Infirmary (Manchester University NHS Foundation Trust) and The Christie Hospital will be undertaken to identify sinonasal carcinoma tumours consecutively between 2016 and 2019. Only tumours originating in the sinonasal tract will be included. To qualify for inclusion, patients will be required to have a diagnosis of a sinonasal carcinoma and have undergone resection surgery with available histological slides and archived (formalin-fixed paraffin-embedded (FFPE)) tissue for analysis. Additionally, the same inclusion criteria will be applied to samples from Head and Neck 5000 (Bristol) and Liverpool. 

    Exclusion Criteria

    Patients with cutaneous or nasopharyngeal tumours or metastasis into the sinonasal tract will be excluded. Only adults will be included in this study.

    How many Groups in study?

    N/A

    Primary Endpoint

    What are the key genetic mutations associated with cancer of the sinonasal tract (sinonasal carcinoma)?

    Secondary outcome

    Are there consistent genetic mutations associated with key clinical outcomes?

    Are consistent genetic mutations or clinical outcomes correlated with the presence of a virus (the Human papilloma virus) which has previously been recognised as a risk factor for oral cancer?

    Treatment plan

    N/A

MOAT (Mode of Action Transgene)

Principle Investigator: Professor Christian Ottensmeier, (Liverpool Head and Neck Centre, UK)

Outline: A multicentre, open-label, dose-escalating, phase Ib, neoadjuvant study of intravenous dosing of NG-641 (oncolytic adenoviral vector expressing FAP-TAc and immune enhancer module)

For: Newly diagnosed or recurrence of clinical stage III-IVb, histologically confirmed oral cacvity, larynx, hypopharynx or oropharynx squamous cell carcinoma (T1N2-3, T2N2-3, T3N0-3, T4aN0-3), considered resectable.

PATHOS

Chief investigator: Professor Mererid Evans (Velindre NHS Trust & Cardiff University, UK) & Professor Terry Jones (Liverpool Head & Neck Centre, UK)

Outline: Standard care VS reduced intensity adjuvant treatment for HPV +ve oropharyngeal squamous cell carcinoma

For: TNM stage T1-T3, N0-N2b HPV positive tumours of the oropharynx

  • Phase of study

    PHASE II/III

    What is the study treatment?

    Standard care VS reduced intensity adjuvant treatment for HPV +ve OPSCC 

    Patient Group

    Inclusion

    • Histologically SCC of the oropharynx 

    • HPV positive on central testing 

    • TNM stage T1-T3, N0-N2b tumours of the oropharynx

    • Local MDT decision to treat with primary TOLR and ND 

    • Patients considered fit for surgery and adjuvant treatment by the local MDT

    • Aged 18 or over 

    • Written informed consent provided 

    Exclusion

    • HPV negative SCC H&N 

    • Patients with T4 primary oropharyngeal tumours and/or T1-T3 tumours where transoral surgery is considered not feasible

    • N2c-N3 nodal disease 

    • Unresectable retropharyngeal node involvement 

    • Current smokers with N2b disease (including smokers up to 2 years before diagnosis) 

    • Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction

    • Patients with distant metastatic disease (AJCC TNM stage IVC disease) as determined by routine pre-operative staging radiological investigations e.g, CT thorax and upper abdomen or PET-CT

    • Patients with a history of malignancy in the last 5 years, except basal cell carcinoma of the skin or carcinoma in-situ of the cervix

    • Women who are pregnant or breastfeeding

    How many Groups in study?

    Group ALow risk – excluded

    Group BIntermediate risk – 

    60gy/30# vs 50gy/25#

    Group CHigh risk

    POCRT 60gy/30# + Cisplatin

    Vs

    PORT – 60gy/30# alone

    Primary endpoint

    Phase II patient reported swallowing outcome at 12 months following treatment (MDADI).

    Secondary outcome

    Swallowing panel measurements qualitative and quantitative swallowing assessments as described.
    QOL – EORTC,QLQ,C30,HN 35.
    Acute and late toxicity CTCAE 4.03
    Overall survival, disease free survival, locoregional control,distant mets.
    Phase III – Overall survival.

    Follow up

    5 years post treatment.

    Year 1 – 4-6 weekly
    Year 2 – every 8-10 weeks
    Year 3 – every 3-5 months
    Year 4 – approx every 6 months
    Year 5 – approx every 6 months

    Videofluoroscopy and water swallow test 

    Baseline  
    4 weeks
    post surgery prior to adjuvant treatment
    12 months post treatment
    24 months post treatment

PROMOTE

Chief investigator: Professor Jo Patterson (Liverpool Head & Neck Centre, UK)

Outline: Promoting Physical Activity For Patients Living With or Beyond Head and Neck Cancer: A Mixed Methods Approach Addressing Health Inequalities and Factors Impacting Behaviour Change

For: Patients living with or previously treated head and neck cancer

  • Phase of study

    N/A

    Patient Group

    Inclusion Screening period

    How many Groups in study?

    3

    • Health professionals 

    • Patients 

    • Care group

    Primary endpoint

    The primary objective of the project is to develop and produce evidence-based guidelines to promote physical activity for people living with and beyond head and neck cancer.

    Secondary outcome

    To systematically review the literature describing: 

    • Current policy and guidance informing physical activity for cancer patients. 

    • The effectiveness of interventions promoting physical activity for patients living with and beyond cancer and the evidence surrounding its implementation for head and neck cancer patients. 

    • Psychological, social, environmental and physical factors that act as barriers or facilitators to physical activity. 

    • The implementation of interventions.

    Treatment plan

    The aim of this study is to replicate similar methodology from the (Chatterjee et al., 2017) study that measured general practitioners knowledge, use and confidence in national physical activity and health guidelines and tools, and apply this to a broad range of health care professionals within the context of head and neck cancer.

RAPTOR

Chief investigators: Professor Richard Shaw & Mr Mandeep Bajwa (Liverpool Head & Neck Centre, UK)

Outline: Randomised Controlled Trial of PENTOCLO (Pentoxifylline, Tocopherol & Clodronate) in Mandibular Osteoradionecrosis

For: Patients with established mandibular osteoradionecrosis following previous radiotherapy.

SAVER

Chief investigator: Professor Richard Shaw (Liverpool Head & Neck Centre, UK)

Outline: Sodium Valproate for Epigenetic Reprogramming in the Management of High Risk Oral Epithelial Dysplasia: a randomised, unblinded, controlled clinical trial with embedded mechanistic and feasibility studies

For: Patients with a diagnosis of oral epithelial dysplasia confirmed via 5mm punch biopsy

  • Phase of study

    PHASE II

    110 participants

    What is the study treatment?

    Sodium Valproate 

    Treatment Arm: Oral sodium valproate gastro resistant 1000mg/day (500mg twice daily). Intervention given for 4 months; including ‘step-up’ phase for the first 2 weeks, at 500mg once daily. 

    Control Arm: No medication received

    Patient Group

    Suspected or confirmed oral dysplasia for screening

    1. 1.  A diagnosis of oral epithelial dysplasia confirmed via 5mm punch biopsy reported by SAVER trial pathologist. The index lesion must be considered to be at high risk (i.e. estimated >20% over 5 years) of malignant transformation, i.e.:

      a.    WHO severe OED or

      b.    WHO mild or moderate OED, with at least one additional high risk feature(s) from the list below:

                                                 i.    non-smoker (less than 100 cigarettes or equivalent over whole lifetime)

                                               ii.     lesion size >200mm2

                                              iii.    lateral tongue site

                                              iv.    mucosal speckling or heterogeneous appearance

                                               v.     excised OSCC during previous 5 years (but not within previous 6 months).

      2.    An index lesion* which must be:

      a.    Accessible

      b.    Measurable

      c.     Amenable to clinical photography

      d.    Oral cavity, lip or oropharynx

      e.    Minimum lesion size: 10mm x 10mm, or >=100mm2

      (* other ‘non-index’ lesions in the same patient may be present and do not make the patient ineligible)

      3.    Treatment plan for either surgical resection, or for surveillance of the lesion by means of clinical and photographic follow-up.

      4.    The patient is fully informed, has received PIS (Patient Information Sheet) & considered during a ‘cooling-off’ period, is competent to consent, and is able to comply with minimum attendance requirements.

      5.    Age ≥ 18 years.

    Exclusion Criteria

    1.    Synchronous or metachronous OSCC (i.e. at time of screening or within 6 months)

    2.    Active malignancy outside head and neck region (with exception of non-melanoma skin cancer)

    3.    OSCC susceptible conditions e.g. Fanconi Anaemia, Blooms syndrome, Ataxia Telangectasia, Li Fraumeni syndrome etc.

    4.    Clinical and/or histopathological diagnosis of oral submucous fibrosis

    5.    Immunosupression, however, low dose i.e. <10mg/day prednisolone, or equivalent steroid, (as per BNF conversion table), are not considered an exclusion.

    6.    Chronic previous or current use of Sodium Valproate

    7.    Diagnosed epilepsy that has chronic previous or current use of any antiepileptic therapy

    8.    Obesity (Body Mass Index >= 30)

    9.    Known relative or absolute contraindications to Sodium Valproate (as listed in British National Formulary), and specifically:

    10.   SAVER Protocol V9.0, 19.04.2021 Based on LCTC Protocol Template v1, 20/02/2020 IRAS ID: 236218 Page 24 of 81

    a.    Acute porphyria

    b.    Known or suspected mitochondrial disorders

    c.     Personal or family history of severe hepatic dysfunction, current hepatic dysfunction (as evidenced by LFTs outwith reference range and prolonged prothrombin time)

    d.    Past history or current pancreatitis

    e.    Women with child-bearing potential. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.

    f.      Potential drug interactions (particularly antipsychotic and anticonvulsant medications, MAO inhibitors, antidepressants, benzodiazepines), specifically patients taking phenobarbital, primodone, carbopenem antibiotics (imipenem, panipenem, meropenem), cimetidine, erythromycin, lamotrigine, olanzapine, pivmecillinam, sodium oxybate, zidovudine, carbamazepine, phenytoin, rifampicin, high dose salicylates including aspirin >75mg daily (patients taking low dose aspirin 75mg daily are eligible)

    g.    Patients with suicidal ideation and behaviour should be excluded from the trial. Patients should also be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

    h.    Patients with known or suspected mitochondrial

    11.  Women who have undergone total hysterectomy or bilateral salpingo-oophorectomy or who are in a postmenoposal state are eligible for the SAVER trial. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range will be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy (HRT). Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal status before study enrolment. Otherwise, they must be considered non-eligible to participate in this trial and excluded.

     

    How many Groups in study?

    2

    Study tx vs control SoC

    Primary Endpoint

    Clinical activity, measured using the commonly used surrogate end point comprising a composite of 

    • changes in lesion size, 

    • histological grade, and 

    Secondary outcome

    • WHO grade of OED in trial biopsies, and also within the entire resection specimen (where any oral resection is performed within trial period) 

    • Histopathological evidence of malignant transformation (OSCC) in index lesion or other H&N site within the 6 month ‘on-trial’ window, and, separately, 

    • Histopathological evidence of malignant transformation (OSCC) in index lesion or other H&N site within the total period of time that SAVER remains open. 

    • Feasibility of the trial, defined by: o the rate of recruitment per centre, 

      • the rate of recruitment for the trial as a whole, 

      • compliance with treatment 

      • drop-out 

    • Mechanistic endpoints: i.e. define the changes in gene expression and epigenetic markers, at both tissue specific and systemic level, accompanying sodium valproate monotherapy. 

      Qualitative endpoints: an embedded qualitative interview study to systematically

    Treatment plan

    Treatment Arm: Oral sodium valproate gastro resistant 1000mg/day (500mg twice daily). Intervention given for 4 months; including ‘step-up’ phase for the first 2 weeks, at 500mg once daily. 

    Control Arm: No medication received

    Adverse events and SAE’s

    To be recorded from consent to 100 days post last dose

SLNB

Chief investigator: Professor Richard Shaw (Liverpool Head & Neck Centre, UK)

Outline: Outcomes following neck surgery in oral cancer: Understanding the contribution of sentinel node biopsy

For: Early stage T1-2 clinically node negative oropharyngeal squamous cell carcinoma

  • Phase of study

    N/A

    Patient Group

    Inclusion Criteria:

    • Early stage T1-2 clinically node negative OSCC. 

    • Treated by SLNB (including both those staged SLNB +ve and SLNB -ve).

    • Or by current standard of care (END or watch and wait).

    • Patients must be at least 6 months post operation at the time of the research observations.

    Exclusion Criteria:

    • Unrelated shoulder or neck morbidity at the time of surgery.

    • Previous unrelated head, neck or shoulder surgery.

    • Previous irradiation of head, neck or shoulder region (prior to index surgery).

    • Recurrence of cancer.

    • Unable to give valid consent.

    • Unable to read / understand English.

    • Age <18yrs.

    How many Groups in study?

    2

    Primary Endpoint

    SLNB vs SoC – shoulder function, appearance, outcomes 

    Adverse events and SAE’s

    When reported how long etc

    N/A

TARGET Head and Neck

Chief Investigator: Professor Christian Ottensmeier, (Liverpool Head and Neck Centre, UK)

Outline: Tissue analysis for understanding head and neck diseases

For: New suspected or confirmed diagnosis of head and neck cancer & non-malignant head and neck diseases

  • Phase of study

    N/A

    What is the study treatment?

    N/A

    Patient Group

    Inclusion criteria

    For the prospective collection of tumour/affected tissue/mucosal tissue/lymph node/lymphoid tissue biopsies and peripheral blood:

    • Suspected or confirmed diagnosis of head and neck cancer, non-malignant head and neck diseases,

    • Patient aged 18 or over

    • Patients with the ability to understand the study requirements and provide written informed consent.

    • Patient scheduled to undergo diagnostic procedure – Direct/Endoscopic/CT or USS guided biopsy/

    • Head and Neck surgery

    Exclusion criteria for dedicated research procedures

    • Patient deemed medically unfit for sample collection

    • Patient with a contraindication for study procedures or sampling

    • The absence/withdrawal of consent

    How many Groups in study?

    N/A

    Primary Endpoint

    The objective of the study proposed here is to define properties of SARS-CoV-2 reactive TRM cells from cancer and non-cancer patients with or without previous SARS-CoV-2 infection and to assess the impact of SARS-CoV-2 infection on anti-tumour and other anti-viral TRM responses. Comparison with virus-reactive circulating T cells will help define features that are specific to tissue-resident T cells. In addition the role of other immune cell types will be examined.

    This project is part of a greater stratified goal of improving the outcome of viral and cancer treatment by optimising choice and efficacy of immunotherapy based on the detailed understanding of the molecular pathology of the individual.

    Treatment plan

    N/A

    Follow up period

    N/A

    Adverse events and SAE’s


    When reported how long etc

    Only during study involvement 

The HNL-PRO project

Chief investigator: Professor Jo Patterson (Liverpool Head & Neck Centre, UK)

Outline: Head and neck lymphoedema patient reported outcomes

For: Patients with a diagnosis of head and neck lymphoedema following prior head and neck cancer treatment   

  • Phase of study

    N/A

    What is the study treatment?

    The primary aim of this study is to retrospectively analyse the experiences of patients with HNL with regards to symptoms, concerns, and overall impact of HNL on function and quality of life.

    The secondary aim is to develop a validated patient reported outcome tool for evaluation of HNL.

    Patient Group

    Inclusion: 

    • Diagnosis of HNL

    • Male and female aged 18 years old and above

    • Have undergone head and neck cancer treatment 

    • Have access to an electronic device for video interview

    • Able to read and understand good English in order to give informed consent and participate in interview

    Exclusion: 

    • Non-English speaking

    • <18 years of age

    • No access to electronic device and/or internet for participation in interviews

    • No history of head and neck lymphoedema

    • Patients unable to give informed consent

    Primary Endpoint

    The primary aim of this study is to retrospectively analyse the experiences of patients with HNL with regards to symptoms, concerns, and overall impact of HNL on function and quality of life.

    The secondary aim is to develop a validated patient reported outcome tool for evaluation of HNL. 

    Objectives: 

    1. To determine the lived experiences of patients with HNL.

    2. To develop a validated HNL patient reported outcome tool.

The PE-HaNC study

Chief investigator: Mr. Jason Fleming (Liverpool Head & Neck Centre, UK)

Outline: Patient experience of head and neck cancer treatment across multiple sites within a tertiary care unit

For: Patients with a historical diagnosis of head and neck cancer who have undergone surgical treatment at Liverpool Head and Neck Centre and post-operative radiotherapy (PORT) +/- chemoradiotherapy (POCRT) at Clatterbridge Centre

  • Phase of study

    N/A

    What is the study treatment?

    Patient experience of head and neck cancer treatment across multiple sites within a tertiary care unit

    Patient Group

    Inclusion: 

    • Diagnosis of HNC

    • Male and female aged 18 years old and above

    • Have undergone surgical treatment at Liverpool Head and Neck Centre and post-operative radiotherapy (PORT) +/- chemoradiotherapy (POCRT) at Clatterbridge Centre

    • Have access to an electronic device for video interview

    • Able to read and understand good English in order to give informed consent and participate in interview

    Exclusion: 

    • Patients with HNC who have undergone single modality treatment (i.e. surgical treatment OR oncology treatment only)

    • Patients unable to give informed consent

    Objectives

    1. To determine the experiences of HNC patients treated in a hub and spoke care model.

    2. To improve patient care and experience in future service development and re-design.

TRANSGENE

Principle Investigator: Professor Christian Ottensmeier, (Liverpool Head and Neck Centre, UK)

Outline: Immunotherapy – mutanome-directed active immunotherapy

For: New diagnosis of Stage III or IVA SCC oral cavity, oropharynx, hypopharynx or Larynx excluding HPV +ve

  • Phase of study

    PHASE I

    Sample size
    60 patients screening
    30 randomised
    4 UK centres
    2 Centres in France

    What is the study treatment?

    Immunotherapy – mutanome-directed active immunotherapy 
    2 Arm RCT
    ARM A= completion of primary tx
    ARM B = Recurrence

    Patient Group

    Inclusion Screening period

    • New dx Stage III or IVA SCC oral cavity, oropharynx,hypopharynx or Larynx excluding HPV +ve 

    • Patients must have undergone gross total resection of the primary tumour

    • Inclusion for tx phase

    • Completed adjuvant therapy & have post tx CT or MRI and Chest CT documenting CR. 3m after completion of adj tx within 6w prior to randomisation

    • Recovered toxicities

    • ECOG 0 or 1

    • Adequate bloods and GFR

    Screening Exclusion

    • Unknown primary

    • Prior anti-cancer vaccines 

    • Other active malignancy requiring tx

    • Previous Cancer unless in remission within 2 years prior to study entry.

    How many Groups in study?

    2

    Arm A - Vaccine completion of Soc tx
    Arm B – vaccine at tme of recurrence

    Primary Endpoint

    Safety and tolerability

    Secondary outcome

    Failure to provide TG4050 
    Failure to treat with TG4050
    Event free survival
    Tumour recist response with recurrent cancer

    Treatment plan

    D1,D8,D15,D22,D29,D36,D43,Q3

    Adverse events and SAE’s

    ICF signature upto 30 days following the last IMP administration.
    All AE’s and SAE’s followed up until resolution