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 healthExclusion 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
ExclusionPatient 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 TOLRPrimary endpoint
MDADI score
Secondary outcome
Survival status
Follow up
Year 1 – every 6 weeks
Year 2 – every 3 months
Year 3-5 – every 6 monthsVideofluoroscopy 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 20204. 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
SwallowingFollow 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 pointsDetermine 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 A – Low risk – excluded
Group B – Intermediate risk –
60gy/30# vs 50gy/25#
Group C – High 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 monthsVideofluoroscopy 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. 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 etcOnly 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
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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:
To determine the lived experiences of patients with HNL.
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
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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
To determine the experiences of HNC patients treated in a hub and spoke care model.
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
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Phase of study
PHASE I
Sample size
60 patients screening
30 randomised
4 UK centres
2 Centres in FranceWhat is the study treatment?
Immunotherapy – mutanome-directed active immunotherapy
2 Arm RCT
ARM A= completion of primary tx
ARM B = RecurrencePatient 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 recurrencePrimary Endpoint
Safety and tolerability
Secondary outcome
Failure to provide TG4050
Failure to treat with TG4050
Event free survival
Tumour recist response with recurrent cancerTreatment 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