Title: MesoTRAP: A feasibility study comparing video-assisted thoracoscopic partial pleurectomy/decortication with indwelling pleural catheter in patients with trapped lung and pleural effusion due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.
Funder: Department of Health and Social Care

Abstract: Background Malignant Pleural Mesothelioma (MPM) is an incurable cancer affecting the pleural lining of the lungs, closely associated with prior exposure to asbestos. Currently, 2500 new cases occur in the UK per annum and median survival is around 12 months. MPM commonly presents with dyspnoea due to increasing unilateral pleural effusion. Standard palliative care management is fluid drainage via a chest drain and talc pleurodesis. However, if the visceral and parietal pleura are unable to appose, an effective pleurodesis is unlikely. In mesothelioma, tumour is commonly present over the visceral surface of the lung, which prevents the lung from re-inflating &ndash; so called trapped lung (TL). In this situation pleural fluid usually recurs and patients go through repeated cycles of fluid drainage and re-accumulation. TL is a challenging management issue causing significant morbidity and in case series of trapped lung, 13-37% have been due to MPM. Some authorities recommend placement of an indwelling pleural catheter (IPC) under local anaesthesia to facilitate repeated drainage in the community. Others have advocated general anaesthesia video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD) to remove as much tumour from the visceral pleural surface as possible to allow the lung to re-expand to permit a pleurodesis. Recognising that management of dyspnoea due to TL lung in MPM is a significant unmet need, our ultimate aim is to undertake a randomised controlled trial comparing VAT-PD with IPC. However, there are several uncertainties to be addressed prior to a full phase III study: i) How prevalent is TL in MPM? ii) Will patients accept randomisation to IPC or VAT-PD? iii) What is the standard deviation of Visual Analogue Scale scores for dyspnoea and chestpain in each treatment group? (This will be used to estimate parameters that will be included in the sample size estimates for a full trial) Primary Objective: The primary objective is to determine the ability to randomise 36 patients in 18 months into a trial of VAT-PD versus IPC in patients with trapped lung and pleural effusion due to MPM. Secondary objectives: To help inform the design of a full phase III randomised controlled trial we will collect data on: i) The prevalence of trapped lung in patients with MPM ii) Visual Analogue Scale scores for dyspnoea and chest pain and the patterns of change over time in each treatment group iii) Quality of Life data at baseline, 1, 3, 6 and 12 months post randomisation iv) Collection and documentation of Adverse Events Qualitative Assessment Study: In parallel to the main study, a sub-study (20 randomised patients and 10 who decline) will examine patient experience of the interventions and factors influencing patient decisions to participate and accept randomisation or not. Plan of investigation: Six thoracic surgical centres with expertise in carrying out both IPC and VAT-PD along with linked non-surgical referring hospitals, all of whom are previous/existing mesothelioma study collaborators, will be invited to participate. Inclusion criteria: confirmed MPM; trapped lung (>20% of one hemithorax without lung markings on chest x-ray) following fluid drainage; deemed suitable for VAT-PD by a thoracic surgeon. Following REC approval, a trial management group, trial steering committee, data monitoring committee will provide governance. The study will be registered with an International Standard Randomised Controlled Trial Number (ISRCTN) and ClinicalTrials.gov Potential benefits to patients and the NHS: The feasibility study will provide information as to a) whether a full randomised controlled trial is achievable in a reasonable time frame, b) the number of patients required. A full trial will determine best management of trapped lung in MPM. This will inform clinicians and policy makers (e.g. NICE and Cochrane reviews).

Lay abstract: Malignant pleural mesothelioma is a cancer, caused by asbestos, affecting 2500 UK patients each year. The main symptom is breathlessness caused by fluid building up in the space between the lung and the chest wall. Treatment involves draining fluid to allow the lung to re-expand. However, sometimes tumour growing over the surface of the lung prevents it from re-expanding. This trapped lung results in fluid re-accumulation and repeated drainage leading to significant patient distress and multiple hospital visits. One approach to dealing with trapped lung in mesothelioma is to insert a thin tube (Indwelling Pleural Catheter) into the space around the lung. The tube can stay in place for a long time allowing patients to drain off fluid at home. The other approach is a keyhole surgical operation to remove as much tumour as possible from the lining of the lung to allow it to re-expand. We do not know whether fitting a tube or the operation is most effective at relieving breathlessness. We want to undertake a study to find out which approach is best. First we need to do a small study to determine whether we can recruit 36 patients in 18 months. We will collect information on how common trapped lung really is and examine quality of life before and after treatment as well as safety aspects. A sub-study will find out what patients thought about the study in order to improve how we run the full-scale study. Research into breathlessness caused by mesothelioma has been identified by the James Lind Alliance Priority Setting Partnership. We received advice on study design from patients/carers and patient support groups. We will make our findings known through patient support groups, scientific journals, national and international conferences. The results will be used to decide whether a larger study should be done.

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