Title: A feasibility randomised controlled trial of pre-treatment gastrostomy tube versus oral feeding plus as-needed nasogastric tube feeding in patients undergoing chemoradiation for head and neck cancer (TUBE trial)
Funder: Department of Health (England)

Abstract: Aims and objectives:Our principal aim is to determine whether a definitive RCT in head and neck cancer patients undergoing chemoradiation comparing prophylactic gastrostomy tube feeding versus oral feeding plus as-needed nasogastric tube feeding is feasible. Design:A mixed methods multicentre study to establish the feasibility of a randomised controlled trial of feeding methods in patients with stage III and IV head and neck cancer receiving chemoradiation therapy with curative intent. The work will be conducted over 24 months.The components are:1. A multicentre randomised controlled feasibility trial comparing pre-treatment gastrostomy versus oral plus as required nasogastric tube feeding in patients with HNSCC.2. A qualitative process evaluation to inform the trial design by investigating patient carer and staff experiences of trial participation3. A modelling exercise to synthesise available evidence and provide estimates of cost-effectiveness and value of informationSetting: Three tertiary NHS centres for HNSCC two in the north and one in the south of England. For our definitive trial additional centres will be recruited via our links with the National Cancer Research Network Comprehensive Clinical Research Network and from respondents to our national survey [1].Target population: Patients with stage III and IV HNSCC who are suitable for primary CRT with curative intent.Inclusion criteria: 1. Grade 1 pre-treatment dysphagia as defined by Common Terminology Criteria for Adverse Events v4.0 (defined as: asymptomatic / symptomatic / able to eat regular diet) 2. consent to be randomised.Exclusion criteria: Patients who 1. decline to participate; 2. unable to give informed consent 3. cannot receive a gastrostomy for medical reasons 4. do not receive treatment with curative intent and 5. patients with malnutrition requiring immediate initiation of enteral feeding. Clinical experience suggests that patients with primary sites in the oropharynx larynx nasopharynx and unknown primaries are those who will fulfil the inclusion criteria (~35% to 40% of all patients).Health technologies being assessed:Pre-CRT gastrostomy arm: Endoscopic or radiologic gastrostomy will be placed before commencement of CRT. Given the pragmatic nature of this study and equivalent success rates with either technique the choice of method of insertion will be left to local protocols of the treating centre.No pre-CRT gastrostomy arm: This group will continue with oral feeding or have a nasogastric tube if required during treatment. The decision to place a nasogastric tube will be based on clinical assessment and patient request. Patient request for gastrostomy tube in this group will also or further lead to gastrostomy placement. Based on published prospective data we anticipate that <10% will convert from NG tube to G tube during the study.Measurement of costs and outcomes:No core outcomes for swallowing in head and neck cancer have been established by the COMET initiative. This feasibility RCT will:1. Assess willingness to randomise be randomised2. Assess retention and drop-out rates from each arm3. Refine interventions and study processes to inform definitive trial design4. Estimate parameters to inform sample size for a definitive trial5. Assess value of information based on modelling exerciseSample size: Each centre has an annual case load of around 180 HNSCC of whom around 40% will receive CRT with curative intent for stage III/IV cancer giving us approximately 162 patients across three sites in the 9 month proposed recruitment period. Research studies take some time to become embedded into practice. We calculate recruitment across the whole trial based on randomisation rate of 0.2 in the first 3months (n=11) and 0.4 in the second 3 months (n=22) with full rate 0.5 ratio recruitment in the last 3 pilot months (n=27). We thus aim to recruit at least 60 subjects (30 per arm of the study). As a feasibility study we aim to provide an assessment of attrition rate within the study to inform future trial design; attrition occurs as survival at 12 months following treatment in advanced head and neck cancer (which forms our cohort) is between 70% and 80% with mortality caused by progressive cancer complications of treatment and other concurrent comorbidity. This sample size will enable the overall rate to be estimated with a 95% confidence interval of no wider than +/-13% (for an attrition rate of 50%). Should the achieved attrition rate be 35% this confidence interval would range from 23% to 48%. For an attrition rate of 20% this confidence interval would range from 11% to 32%. An estimate of recruitment rate is dependent on the number of patients approached; should a 50% rate be observed (120 patients approached to recruit 60 patients) this would correspond to a 95% confidence interval of width +/-9%.Project timetables including recruitment rate:-6 to 0 months: develop patient recruitment materials with patient panel obtain ethical approval. 3 months set up time; 9 months recruitment (months 4 to 12); 6 months follow up for all recruits (8 months from date of randomisation to allow for treatment completion). This works out to total of 20 months from day one to end of data collection; months 21-24 for data analysis preparation of presentations publications and grant application for definitive trial = 24 months total duration. Flow diagram: This attached in the uploaded documents.Team expertise:The TUBE team has a track record of delivering collaborative work. The multiple disciplines in the team include surgical and medical oncology speech and swallowing therapy dietetics health economics social sciences statistical expertise and expert trialists. We have purposely chosen centres with different practices regarding enteral feeding at treatment commencement. The Clinical Trials Units supporting this application also have an excellent pedigree of delivering successful work. We have involved patients in research design published a review of the literature [2] and conducted a national survey [1]. We have drawn upon a highly regarded PhD thesis [3] of one of the TUBE team (JP) established a multicentre audit on tube feeding validated new outcome measures and have obtained support for the project at National Cancer Research Institute meetings. Professor June Corry who led the Australian RCT has consented to act as advisor.


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS