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Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma
  1. Eric Lim1,
  2. Liz Darlison2,3,
  3. John Edwards4,
  4. Daisy Elliott5,
  5. D A Fennell6,
  6. Sanjay Popat7,
  7. Robert C Rintoul8,
  8. David Waller9,
  9. Clinton Ali10,
  10. Andrea Bille11,
  11. Liz Fuller12,
  12. Andreea Ionescu13,
  13. Manjusha Keni14,
  14. Alan Kirk15,
  15. Pek Koh16,
  16. Kelvin Lau9,
  17. Talal Mansy17,
  18. Nick A Maskell18,19,
  19. Richard Milton20,
  20. Dakshinamoorthy Muthukumar21,
  21. Tony Pope22,
  22. Amy Roy23,
  23. Riyaz Shah24,
  24. Jonathan Shamash25,
  25. Zacharias Tasigiannopoulos26,
  26. Paul Taylor27,
  27. Sarah Treece28,
  28. Kate Ashton29,
  29. Rosie Harris29,
  30. Katherine Joyce29,
  31. Barbara Warnes29,
  32. Nicola Mills5,
  33. Elizabeth A Stokes30,
  34. Chris Rogers29
  35. On behalf of MARS 2 Trialists
    1. 1Academic Division of Thoracic Surgery, Royal Brompton and Harefield NHS Trust, London, UK
    2. 2The Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK
    3. 3Mesothelioma UK, Glenfield Hospital, Leicester, UK
    4. 4Cardiothoracic Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
    5. 5Population Health Sciences, University of Bristol, Bristol, UK
    6. 6Cancer Research UK Centre Leicester, University Hospitals of Leicester NHS Trust, Leicester, UK
    7. 7Department of Medicine, Royal Marsden NHS Foundation Trust, London, UK
    8. 8Department of Thoracic Oncology, Papworth Hospital NHS Foundation Trust, Cambridge, UK
    9. 9Department of Thoracic Surgery, Barts Health NHS Trust, London, UK
    10. 10The Beatson West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK
    11. 11Thoracic Surgery, Guy’s and Saint Thomas’ Hospitals NHS Trust, London, UK
    12. 12Respiratory Medicine, South Tyneside NHS Foundation Trust, South Shields, UK
    13. 13Lung Cancer, Aneurin Bevan University Health Board, Newport, UK
    14. 14Oncology, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
    15. 15Department of Thoracic Surgery, Golden Jubilee National Hospital, Clydebank, UK
    16. 16Department of Oncology, New Cross Hospital, Wolverhampton, UK
    17. 17Oncology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK
    18. 18Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
    19. 19Respiratory Research Unit, North Bristol NHS Trust, Westbury on Trym, UK
    20. 20Thoracic Surgery Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK
    21. 21Oncology, Colchester Hospital University NHS Foundation Trust, Colchester, UK
    22. 22Clatterbridge Cancer Centre, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK
    23. 23Plymouth Oncology Centre, University Hospitals Plymouth NHS Trust, Plymouth, UK
    24. 24Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK
    25. 25Department of Medical Oncology, Barts Health NHS Trust, London, UK
    26. 26The Oncology Care Team, Norfolk and Norwich University Hospital NHS Trust, Norwich, UK
    27. 27Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
    28. 28Heamatology and Oncology Unit, North West Anglia NHS Foundation Trust, Peterborough, UK
    29. 29Bristol Trials Centre (CTEU), University of Bristol, Bristol, UK
    30. 30Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
    1. Correspondence to Eric Lim; e.lim{at}rbht.nhs.uk

    Abstract

    Introduction Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.

    Methods and analysis The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery—(extended) pleurectomy decortication—versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.

    Ethics and dissemination Research ethics approval was granted by London – Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.

    Trial registration numbers ISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272.

    • oncology
    • chemotherapy
    • thoracic surgery
    • thoracic medicine
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    Footnotes

    • Collaborators MARS 2 Trialists: Project management team members: Athanasia Gravani, Holly McKeon, Wendy Underwood, Rachel Brophy, Nicola Farrar; Papworth Trials Unit Collaboration (pilot study): Victoria Hughes, Jane Elliott, Claire Matthews, Philip Noyes; Participating Sites Members: pilot study and main trial, University Hospitals of Leicester NHS Trust—medical and surgical site (opened 22/04/2015): Apostolos Nakas, Louise Nelson, Sheffield Teaching Hospitals NHS Foundation Trust—medical and surgical site (opened 13/05/2015): Sara Tenconi, Laura Socci, Hilary Wood, Helena Hanratty, Helena Stanley; South Tyneside and Sunderland NHS Foundation Trust—medical site (opened 19/06/2015): Judith Moore; Papworth Hospital NHS Foundation Trust—medical site (opened 01/07/2015): Robert Rintoul, Suzanne Miller, Amy Gladwell, Jenny Castedo, Amanda Stone; Colchester Hospital University NHS Foundation Trust—medical site (opened 03/11/2015): Charlotte Ingle, Hayley Hewer; South Tees Hospitals NHS Foundation Trust—medical site (opened 16/11/2015): Louise Li, Eleanor Aynsley, Andrea Watson, Charlotte Jacobs; The Clatterbridge Cancer Centre NHS Foundation Trust—medical site (opened 25/11/2015): Alison Hassall, Masuma Begum; University Hospitals of Derby and Burton NHS Foundation Trust—medical site (opened 26/11/2015): Christopher Worth, Ellie Piggott, Elizabeth Nadin; Leeds Teaching Hospitals NHS Trust—medical site (opened 02/12/2015): Victoria Ashford-Turner, Matthew Callister, Manchester University NHS Foundation Trust—medical site (opened 21/12/2015): Yvonne Summers, Raffaele Califano, Laura Cove-Smith, Matt Evison, Maria Blinston, Sara Waplington, Amal Ismail, Rachel Chant, Asmita Desai, Juliette Novasio, Marie Kirwan; The Royal Wolverhampton NHS Trust—medical site (opened 04/01/2016): Ian Morgan, Victoria Lake, Nichola Harris; Royal Gwent Hospital, Aneurin Bevan University Health Board—medical site (opened 08/02/2016): Simon Hodge; The Royal Marsden NHS Foundation Trust—medical site (opened 08/04/2016), Chelsea sub-site: Nadia Yousaf, Nadza Tokaca, Adam Januszewski, Avani Athauda, Anisha Ramessur, Emily Grist, Niamh Colman, Michael Flynn, Joan Joyce, Sarah Vaughan, Maria Piga, Derya Sahin, Agnieszka Yongue, Emma Turay, Sutton sub-site: Mary O’Brien, Jaishree Bhosle, Rajiv Kumar, Charlotte Milner-Watts, Jessica Brown, David Walder, Alexandros Georgiou, Xiaorong Wu, Naila Kaudeer, Kroopa Joshi, Michael Davidson, Shelize Khakoo, Bee Ayite, Kathryn Priest, James Dobbyn, Vasanthi Prathapan, Deborah McCrimmon, Natalie Ash, Alison Norton, Bianca Peet, Libby Hennessy, Rosemary Johnson, Laura White; Kingston sub-site: Edward Armstrong, Maria Coakley, Scott Shepherd, Narda Chaabouni, Katherina Sreter, Vasileios Angelis, Mariko Morishita, Jose Roca, Mary Jane de los Reyes Lauigan, Katrin Sainudeen, Helen Morgan; Peterborough City Hospital, North West Anglia NHS Foundation Trust—medical site (opened 16/05/2016): Abigail Hollingdale, Chloe Eddings, Holly Warman; Participating Sites Members: main trial only, Barts Health NHS Trust—medical and surgical site (opened 05/06/2017): Jeremy Steele, Jo Hargrave, Resmi Jayachandran, Pratistha Panday, The Beatson West of Scotland Cancer Centre; Greater Glasgow Health Board—medical site (opened 14/07/2017): Austin McInnes; Golden Jubilee National Hospital—surgical site (opened 14/07/2017): Rocco Bilancia, Julie Buckley, Elizabeth Boyd; North Bristol NHS Trust—medical site (opened 28/02/2018): Natalie Zahan-Evans, Anna Morley; Norfolk and Norwich University Hospitals NHS Foundation Trust—medical site (opened 12/06/2018): Adela Dann, Eleanor Mishra, Pinelopi Gkogkou; University Hospitals Plymouth NHS Trust—medical site (opened 16/07/2018): Irene Harvey, Hilary Congdon; Barking, Havering and Redbridge University Hospitals NHS Trust—medical site (opened 24/07/2018): Alison Ray; Guy’s and St. Thomas’ NHS Foundation Trust—medical and surgical site (opened 10/08/2018): Jehan Mansi, Amy Quinn; Oxford University Hospitals NHS Foundation Trust—medical site (opened 19/10/2018): Najib M Rahman, Jack Seymour, Hannah Ball, Meenali Chitnis; Maidstone and Tunbridge Wells NHS Trust—medical site (opened 19/10/2018): Eirini Petroyannou, Kimberley Snoad, Monica Tavares Barbosa; University Hospitals Birmingham NHS Foundation Trust—medical site (opened 03/01/2019): Gary Middleton, Philip Earwaker, Haider Abbas, Parminder Sohal; Independent Trial Steering Committee members: Marcus Flather, Paul Beckett and Carol Tan have declared the following competing interest: Ethicon endostaplers—consultancies; Fergus Gleeson, Fergus MacBeth, Mavis Nye, Harvey Pass and Pauline Leonard have declared the following competing interests: Teva Amgen, Tom Treasure. Unless otherwise stated above, committee members have declared no competing interests, Independent Data Monitoring and Safety Committee members: Linda Sharples, Valerie Rusch, Mark Britton, Robin Rudd, Joseph S Friedberg, Peter Goldstraw. Unless otherwise stated above, committee members have declared no competing interests.

    • Contributors EL: Study design, preparation and drafting of protocol and manuscript, Chief Investigator for the trial. LD: Study design, preparation of protocol and review of manuscript. JE: Study design, preparation of protocol and review of manuscript, Principal Investigator and acquired data for the study. DE: Design of integrated qualitative study, preparation of study protocol, review of manuscript. DAF: Study design, preparation of protocol and review of manuscript, Principal Investigator and acquired data for the study. SP: Study design, preparation of protocol and review of manuscript, Principal Investigator and acquired data for the study. RCR: Study design, preparation of protocol and review of manuscript, Principal Investigator and acquired data for the study. DW: Study design, preparation of protocol and review of manuscript, acquired data for the study. CA, AB, LF, AI, MK, AK, PK, KL, TM, NAM, RM, DM TP, AR, RS, JS, ZT, PT, ST: Review of manuscript, Principal Investigator and acquired data for the study. KA: Study design, preparation and drafting of protocol and manuscript, oversaw study conduct and acquisition of data. RH: Statistical analysis plan, review of manuscript. KJ: Preparation and drafting of manuscript, oversaw study conduct and acquisition of data. BW: Drafting of manuscript, oversaw study conduct and acquisition of data. NM: Conduct of integrated qualitative study, preparation of study protocol, review of manuscript. EAS: Design of health economic component, preparation of study protocol, review of manuscript. CR: Study design, sample size and statistical analysis plan, drafting of protocol, review of manuscript.

    • Funding This research is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 15/188/31). The pilot study was funded by Cancer Research UK and Mesothelioma UK has contributed towards patient travel expenses. This study was designed and delivered in collaboration with the Bristol Trials Centre Clinical Trials and Evaluation Unit (CTEU), a UK Clinical Research Collaboration (UKCRC) registered clinical trials unit which, as part of the Bristol Trials Centre (BTC), is in receipt of NIHR Clinical Trials Unit (CTU) support funding. DE was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. SP acknowledges NHS funding to the Royal Marsden Hospital/Institute of Cancer Research NIHR Biomedical Research Centre.

    • Disclaimer The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health and Social Care. The funder and sponsor approve any amendments to the study but have no direct involvement in study design; collection, management, analysis and interpretation of data; writing of the report; and the decision to submit this report for publication.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting and dissemination plans of this research. Refer to the Methods section for further details.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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