Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK.

INTRODUCTION: Head and neck cancer is the eighth most common cancer in the UK. Current standard of care treatment for patients with recurrent/metastatic squamous cell head and neck carcinoma (HNSCC) is platinum-based chemotherapy combined with the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, cetuximab. However, most patients will have poor median overall survival (OS) of 6-9 months despite treatment. HNSCC tumours exhibit an immune landscape poised to respond to immunotherapeutic approaches, with most tumours expressing the immunosuppressive receptor programmed death-ligand 1 (PD-L1). We undertook the current study to determine the safety and efficacy of avelumab, a monoclonal antibody targeting the interaction between PD-L1 and its receptor on cytotoxic T-cells, in combination with cetuximab. METHODS AND ANALYSIS: This is a multi-centre, single-arm dose de-escalation phase II safety and efficacy study of avelumab combined with cetuximab; the study was to progress to a randomised phase II trial, however, the study will now complete after the safety run-in component. Up to 16 participants with histologically/cytologically recurrent/metastatic squamous cell carcinoma (including HNSCC) who have not received cetuximab previously will be recruited. All patients will receive 10 mg/kg avelumab and cetuximab (500, 400 or 300 mg/m2 depending on the cohort open at time of registration) on days 1 and 15 of 4-week cycles for up to 1 year, (avelumab not given cycle 1 day 1). A modified continual reassessment method will be used to determine dose de-escalation. The primary objective is to establish the safety of the combination and to determine the optimum dose of cetuximab. Secondary objectives include assessing evidence of antitumour activity by evaluating response rates and disease control rates at 6 and 12 months as well as progression-free and OS. ETHICS AND DISSEMINATION: Approval granted by City and East REC (18/LO/0021). Findings will be published in peer-reviewed journals and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT03494322.

Chin tuck against resistance exercise with feedback to improve swallowing, eating and drinking in frail older people admitted to hospital with pneumonia: protocol for a feasibility randomised controlled study.

BACKGROUND: Swallowing difficulties (dysphagia) and community-acquired pneumonia are common in frail older people and maybe addressed through targeted training of the anterior neck musculature that affects the swallow. We have developed a swallowing exercise rehabilitation intervention (CTAR-SwiFt) by adapting a previously established swallowing exercise to ensure patient safety and ease of execution in the frail elderly population. The CTAR-SwiFt intervention consists of a feedback-enabled exercise ball that can be squeezed under the chin, with real-time feedback provided via a mobile application. The aim of this study is to evaluate the feasibility of assessing the effectiveness of the CTAR-SwiFt intervention in reducing dysphagia and community-acquired pneumonia, prior to a larger-scale multi-centre randomised controlled trial. METHODS: We will recruit 60 medically stable patients over the age of 75 years who have been admitted with a diagnosis of pneumonia to the acute frailty wards at two participating hospitals in the UK. Study participants will be randomised into one of three groups: standard care, low intensity (once daily) CTAR-SwiFt exercise or high intensity (twice daily) CTAR-SwiFt exercises. The intervention period will last for 12 weeks, the final follow-up assessment will be conducted at 24 weeks. We will assess the feasibility outcomes, including rates of participant recruitment and retention, compliance with the exercise regime and adverse incidents. Additionally, we will assess the usability and acceptability of the intervention device and the performance of different clinical outcome measures (e.g. chin tuck strength, Functional Oral Intake Scale, SWAL-QOL, EQ-5D and swallow speed). A sub-sample of study participants will complete videofluoroscopic assessments of swallowing function before and after the intervention to evaluate the physiological changes (e.g. bolus flow rates, laryngeal elevation, base-of-tongue retraction). CONCLUSIONS: By improving the ability to swallow, using our chin tuck exercise intervention, in frail older patients admitted to hospital with pneumonia, it is anticipated that patients' oral intake will improve. It is suggested that this will further impact clinical, patient and healthcare economic outcomes, i.e. reduce the need for supplemental feeding, improve patient satisfaction with oral intake and swallowing-related quality of life, decrease the occurrence of chest infections and reduce hospital admissions and related healthcare costs. TRIAL REGISTRATION: ISRCTN, ISRCTN12813363 . Registered on 20 January 2020.

The multidisciplinary, theory-based co-design of a new digital health intervention supporting the care of oesophageal cancer patients.

OBJECTIVE: Oesophageal cancer patients have complex care needs. Cancer clinical nurse specialists play a key role in coordinating their care but often have heavy workloads. Digital health interventions can improve patient care but there are few examples for oesophageal cancer. This paper aims to describe the multidisciplinary co-design process of a digital health intervention to improve the experience of care and reduce unmet needs among patients with oesophageal cancer. METHODS: A theory-based, multi-disciplinary, co-design approach was used to inform the developmental process of the digital health intervention. Key user needs were elicited using mixed methodology from systematic reviews, focus groups and interviews and holistic need assessments. Overarching decisions were discussed among a core team of patients, carers, health care professionals including oncologists and cancer clinical nurse specialists, researchers and digital health providers. A series of workshops incorporating a summary of findings of key user needs resulted in the development of a minimum viable product. This was further refined after a pilot study based on feedback from end users. RESULTS: The final digital health intervention consists of a mobile app feature for patients and carers connected to a dashboard with supporting additional features for clinical nurse specialist. It contains a one-way messaging function for clinical nurse specialists to communicate with patients, functions for patients to record weight and holistic need assessment results which could be viewed by their clinical nurse specialists as well as a library of informative articles. CONCLUSIONS: The multidisciplinary co-design of a digital health intervention providing support for oesophageal cancer patients and health care professionals has been described. Future studies to establish its impact on patient outcomes are planned.