Clinical Trials

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 2

Treatment

Tigilanol Tiglate

Objectives

Primary Objective:

1. To evaluate tumour ablation following treatment(s) with intratumoural injections of tigilanol tiglate.

Secondary Objectives:

1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate.

2. To evaluate disease control by assessing time to local disease recurrence from last treatment.

3. To evaluate the tumour recurrence rate at injected tumour sites.

4. To evaluate survival by assessing Progression Free Survival (PFS).

Exploratory Objectives:

1. To assess the impact on Quality of Life (QoL).

2. To assess the degree of wound healing after each treatment.

3. To assess the tumour response in injected and non-injected tumours, based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

4. To assess the tumour response according to intratumoural Response Evaluation Criteria in Solid Tumours (itRECIST).

5. To assess changes in tumour biomarkers.

6. To assess the tumour microenvironment.

Eligibility Criteria

Inclusion Criteria:

A patient will be eligible for study participation if they meet ALL of the following criteria:

1. Are willing and able to provide written informed consent for the study prior to any protocol-specific procedures and to comply with all local and study requirements.

2. Are ≥ 18 years of age on the day of providing informed consent.

3. Have a histologically confirmed diagnosis of a solid head and neck malignancy and have either recurrent disease and/or metastatic disease, or have failed on at least one line of systemic therapy. Tumour types can include: HNSCC, sino-nasal cancers, salivary gland cancers, and peri-stomal laryngeal carcinomas with pre-existing tracheostomy.

4. Have disease that is amenable to intratumoural injection either by palpation or under ultrasound guided injection. Lymph nodes with metastatic disease from the patient’s head and neck cancer can be selected for treatment.

Note: Measurable disease as per RECIST v1.1 is not mandatory.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

6. Have life expectancy of more than 12 weeks.

7. Female participants who are Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test at Screening (within 14 days of the first study drug administration), must be willing to use a highly effective contraception from date of consent, throughout the study period and up to 30 days after the last study drug administration, and must not be breastfeeding.

8. Male participants with a potentially fertile female partner are eligible if they have had a vasectomy or are willing to use adequate contraception from prior to commencement of study drug administration, throughout the study period and up to 30 days after the last study drug administration, and must not donate sperm throughout the study period and up to 30 days after the last study drug administration.

Exclusion Criteria:

A patient will be excluded from study participation if they meet ANY of the following criteria:

1. Are planning to receive intratumoural treatment or radiotherapy to any of the tumours intended for injection within 28 days prior to Screening, or during treatment with tigilanol tiglate.

2. Have a tumour intended for injection that is immediately adjacent to, or with infiltration into, any major artery or vein (e.g., if the tumour for injection is located adjacent to the jugular vein).

3. Have a tumour intended for injection located in an area where post-injection swelling could compromise the airway.

4. Have a tumour intended for injection that is a nasal tumour extending into the Ethmoid sinus.

5. Have had any previous intervention (extensive surgery or radiation therapy) in the area of a tumour intended for injection that is in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling).

Patients with a permanent tracheostomy can be included.

6. Are receiving or have received other investigational agents or have used an investigational device without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous investigational therapies to ≤ Grade 1 at baseline.

7. Are receiving or have received systemic anticancer therapy or therapeutic radiation treatment, without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 at baseline.

8. Have had major surgery within 28 days of their first treatment with tigilanol tiglate or anticipate the need for major surgery during the study period. Minor surgical procedures are permitted, but with sufficient time for wound healing.

9. Have known, current or history of active cerebral metastasis and/or carcinomatous meningitis.

10. Have any bleeding diathesis or coagulopathy that would make intratumoural injection or biopsy unsafe, or if they are on therapeutic warfarin therapy.

11. Have a history of allergic reactions or severe hypersensitivity (Grade ≥ 3) attributed to tigilanol tiglate or compounds of similar chemical or biologic composition to tigilanol tiglate or any of its excipients or other agents used in the study.

12. In the opinion of the treating Investigator, they are not an appropriate candidate for the study for any reason (e.g., they have a known psychiatric or substance abuse disorder that would interfere with their ability to cooperate with the requirements of the study).

Objectives

Primary Objective:

1. Ascertain the 2-year disease-free survival post salvage surgery for recurrent/ residual/ new primary head and neck SCC (split cohort of prospective and retrospective patients)

Secondary Objectives:

2. Define the 2- and 5-year overall, disease specific, and local recurrence free survival in retrospectively identified patients undergoing salvage surgery for recurrent/ residual/ new primary head and neck SCC

3. Define the 2 year overall, disease specific and local recurrence free survival in prospectively identified patients undergoing salvage surgery for recurrent/ residual/ new primary head and neck SCC

4. Report on gross functional outcomes by documenting rates of gastrostomy and tracheostomy dependence at 1-year post-salvage surgery.

5. For the prospective cohort assess the overall, speech-related and swallow-related quality-of-life outcomes at pre-operatively and at 6- and 12-months post-surgery using validated questionnaires.

6. Estimate the rates of close and involved surgical margins across all surgical salvage procedures

7. Determine the impact of close and involved margins on survival outcomes

8. Establish the rates of super-selective, selective and modified/ radical salvage neck dissection in clinically N0 and N+ necks

9. Ascertain how the extent of salvage neck dissection influences survival outcomes.

10. Estimate the rate of occult nodal metastasis in clinically N0 necks with locally recurrent disease

11. Describe the impact of neck dissection on survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease

12. Establish the clinical prognostic indicators of negative survival and functional outcomes

Exploratory molecular analysis:

13. Assess the molecular makeup of head and neck tumours that have not responded to radiotherapy treatment, or which recur having previously responded.

14. Comparison of the differences in subclonal architecture, mutational signatures, and loss of heterozygosity between head and neck cancers before and after radiotherapy treatment

15. Assess changes in plasma circulating tumour DNA before and after salvage surgical procedures 16. Correlate Molecular outcomes with clinical outcomes from the cohort study.

Eligibility Criteria

Inclusion Criteria:

• Aged over 18

• Previous H&N SCC treated with radiotherapy

• Recurrent, residual, or new primary SCC of the oropharynx, oral cavity, larynx, and hypopharynx treated with salvage surgery

• Ability to give informed consent for biological sample collection (prospective/ molecular study participants only)

Exclusion Criteria:

• Nasopharyngeal and cutaneous SCC of the H&N

• Thyroid, salivary gland, and non-squamous cell H&N cancers

• Presence of distant metastasis (M1) or surgically inoperable T4b tumours

Planned Sample Size

300 retrospective patients and 100 prospective patients

No limitations will be placed on participants in exploratory molecular analysis

Follow up duration

Up to 2 years clinical follow up for oncological outcomes for the prospective cohort and up to 5 years for the retrospective cohort.

Planned Trial Period

• Retrospective- consecutive patients will be identified and recruited from 1st January 2016 until 31st December 2021 (salvage surgery between these dates).

• Prospective- identification and recruitment of patients will take place over 15 months from September 2023 until 1st November 2024 inclusive.

• Prospective patient’s will be followed up for a minimum of two years following their surgery. The proposed end date of the study is 1st November 2026. The overall proposed study duration is 3.5 years.

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

Objectives

Primary Objectives:

• To establish the relative effects of oral, intratympanic, or combined oral and intratympanic steroids on hearing recovery in idiopathic sudden sensorineural hearing loss (ISSNHL), when used as first line management.

Secondary Objectives:

• To complete a health economic assessment of the different routes of steroid administration.

• To use participant submitted data to explore the trajectory to hearing recovery.

What is the study treatment?

• Oral steroid (Prednisolone) 1mg/kg/day up to 60mg/day for 7 days; Or

• Intratympanic steroid (Dexamethasone) three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; Or

• Combined oral (Prednisolone) and intratympanic (Dexamethasone) steroid as described above, with the first intratympanic injection occurring within 4 days of starting oral steroid use.

How many groups are there in the study?

3

Patient Group

Inclusion Criteria:

• Adults aged 18 years or over

• Diagnosis of new-onset ISSNHL- sensorineural hearing loss of 30 decibels (dBHL) or greater occurring within a 3-day period and including 3 contiguous pure-tone frequencies (out of 0.5, 1.0, 2.0, 4.0 kilohertz (kHz)) confirmed with a pure tone audiogram.

• Onset of hearing loss within four weeks prior to randomisation

• English spoken as a first or second language

Exclusion Criteria:

• Identified cause for hearing loss (not idiopathic) e.g. Meniere’s

• Bilateral ISSNHL

• Received prior steroid treatment for the same episode of ISSNHL

• Medical contraindication to high dose systemic steroids

• Previous history of psychosis

• On oral steroid therapy for another condition

• Known adrenocortical insufficiency other than exogenous corticosteroid therapy

• Hypersensitivity to the active substance or to any of the excipients

• Has a systemic infection unless specific anti-infective therapy is employed

• Has ocular herpes simplex

• Has ipsilateral acute or chronic active middle ear disease (including acute otitis media, chronic suppurative otitis media and cholesteatoma, excluding dry perforation)

• Does not have the capacity to provide written informed consent

Outcome Measures

Primary Outcome

• The absolute improvement in pure tone audiogram average at 12-weeks following treatment initiation (calculated at 0.5, 1.0, 2.0, 4.0 kHz dBHL). Conducted by an audiologist blinded to the treatment allocation.

Secondary Outcomes

• Functional hearing:

o SSQ (Speech, Spatial and Qualities of hearing questionnaire)

o Pure tone audiogram average at 6-week

o Pure tone audiogram average across 4.0, 6.0 and 8.0 kHz,

o AB phoneme score

• High frequency hearing threshold measured by the absolute improvement in pure tone audiogram average across 4.0, 6.0 and 8.0 kHz.

• Extent of hearing recovery

• Time to recovery

• Associated Symptoms: dizziness and tinnitus (VRBQ & TFI).

• Adverse Events

• Health Economics (HUI3, ICECAP-A, Resource usage)

Optional

• Weekly home hearing tests (speech and pure tone thresholds) online

Follow Up

12 weeks

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?

N/A

Patient Group

Inclusion criteria:

Patients willing to perform and consent to the following:

• Have their voice digitally recorded in a clinic room while slowly counting from 1 -20.

• Have their breath sounds recorded after taking 2 successive sharp inspiratory breaths.

Exclusion criteria:

• Patients not wishing to participate.

• Patients who cannot give consent.

How many Groups in study?

N/A

Aims

1. To determine the utility of voice recordings in correctly identifying patients with head and neck cancer when combined with patient symptoms and demographics.

2. To assess the ability of head and neck surgeons to diagnose patients’ underlying laryngeal or oropharyngeal disorders based on an analysis of voice recordings, symptoms and demographics.

Outcomes

Correctly risk stratify patients into malignant or benign groups based on clinician validation of voice recordings and clinician review of patient symptoms and demographics as detailed in the standardized GP referral document (NG12).

Follow up period

N/A

Adverse events and SAE’s

N/A