Clinical Trials

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

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
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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

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.

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

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.

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

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 

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.