{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:24:35Z","timestamp":1791955475104,"version":"4.3.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C16728\/A21400"],"award-info":[{"award-number":["C16728\/A21400"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001009","name":"Bristol-Myers Squibb Foundation","doi-asserted-by":"publisher","award":["CA209-841"],"award-info":[{"award-number":["CA209-841"]}],"id":[{"id":"10.13039\/100001009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13063-018-2602-y","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T08:05:14Z","timestamp":1524038714000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial"],"prefix":"10.1186","volume":"19","author":[{"given":"Dean A.","family":"Fennell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-1605","authenticated-orcid":false,"given":"Emma","family":"Kirkpatrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Cozens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mavis","family":"Nye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Lester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Szlosarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Danson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ottensmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihalis","family":"Kalevras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Maishman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"issue":"6","key":"2602_CR1","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S1470-2045(04)01492-5","volume":"5","author":"DA Fennell","year":"2004","unstructured":"Fennell DA, Rudd RM. Defective core-apoptosis signalling in diffuse malignant pleural mesothelioma: opportunities for effective drug development. Lancet Oncol. 2004;5(6):354\u201362.","journal-title":"Lancet Oncol"},{"issue":"3","key":"2602_CR2","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ncponc1039","volume":"5","author":"DA Fennell","year":"2008","unstructured":"Fennell DA, et al. Advances in the systemic therapy of malignant pleural mesothelioma. Nat Clin Pract Oncol. 2008;5(3):136\u201347.","journal-title":"Nat Clin Pract Oncol"},{"issue":"28","key":"2602_CR3","doi-asserted-by":"publisher","first-page":"6881","DOI":"10.1200\/JCO.20005.14.589","volume":"23","author":"JP van Meerbeeck","year":"2005","unstructured":"van Meerbeeck JP, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005;23(28):6881\u20139.","journal-title":"J Clin Oncol"},{"issue":"14","key":"2602_CR4","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","volume":"21","author":"NJ Vogelzang","year":"2003","unstructured":"Vogelzang NJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636\u201344.","journal-title":"J Clin Oncol"},{"issue":"10026","key":"2602_CR5","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","volume":"387","author":"G Zalcman","year":"2016","unstructured":"Zalcman G, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10026):1405\u201314.","journal-title":"Lancet"},{"issue":"10027","key":"2602_CR6","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","volume":"387","author":"RS Herbst","year":"2016","unstructured":"Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540\u201350.","journal-title":"Lancet"},{"key":"2602_CR7","doi-asserted-by":"crossref","unstructured":"Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497\u2013508.","DOI":"10.1016\/S1470-2045(16)30498-3"},{"key":"2602_CR8","doi-asserted-by":"crossref","unstructured":"Reck M, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823\u201333.","DOI":"10.1056\/NEJMoa1606774"},{"issue":"7","key":"2602_CR9","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1097\/JTO.0000000000000177","volume":"9","author":"AS Mansfield","year":"2014","unstructured":"Mansfield AS, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9(7):1036\u201340.","journal-title":"J Thorac Oncol"},{"issue":"11","key":"2602_CR10","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/j.jtho.2016.07.033","volume":"11","author":"S Khanna","year":"2016","unstructured":"Khanna S, et al. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the Anti-PD-L1 antibody avelumab. J Thorac Oncol. 2016;11(11):1993\u20132005.","journal-title":"J Thorac Oncol"},{"issue":"7528","key":"2602_CR11","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/nature13954","volume":"515","author":"PC Tumeh","year":"2014","unstructured":"Tumeh PC, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568\u201371.","journal-title":"Nature"},{"issue":"5","key":"2602_CR12","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/S1470-2045(17)30169-9","volume":"18","author":"EW Alley","year":"2017","unstructured":"Alley EW, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):623\u201330.","journal-title":"Lancet Oncol"},{"issue":"15_Suppl","key":"2602_CR13","doi-asserted-by":"crossref","first-page":"8503","DOI":"10.1200\/JCO.2016.34.15_suppl.8503","volume":"34","author":"R Hassan","year":"2016","unstructured":"Hassan R, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase Ib trial: safety, clinical activity, and PD-L1 expression. J Clin Oncol. 2016;34(15_Suppl):8503.","journal-title":"J Clin Oncol"},{"issue":"1","key":"2602_CR14","doi-asserted-by":"publisher","first-page":"S292","DOI":"10.1016\/j.jtho.2016.11.300","volume":"12","author":"J Quispel-Janssen","year":"2017","unstructured":"Quispel-Janssen J, et al. OA13.01 A phase II study of nivolumab in malignant pleural mesothelioma (NivoMes): with Translational Research (TR) biopies. J Thorac Oncol. 2017;12(1):S292\u20133.","journal-title":"J Thorac Oncol"},{"issue":"4","key":"2602_CR15","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S1470-2045(15)70056-2","volume":"16","author":"LM Krug","year":"2015","unstructured":"Krug LM, et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015;16(4):447\u201356.","journal-title":"Lancet Oncol"},{"issue":"5","key":"2602_CR16","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.jtho.2017.02.013","volume":"12","author":"B Thapa","year":"2017","unstructured":"Thapa B, et al. The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma. J Thorac Oncol. 2017;12(5):850\u20139.","journal-title":"J Thorac Oncol"},{"issue":"6","key":"2602_CR17","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1177\/1740774506073467","volume":"3","author":"SJ Pocock","year":"2006","unstructured":"Pocock SJ. Current controversies in data monitoring for clinical trials. Clin Trials. 2006;3(6):513\u201321.","journal-title":"Clin Trials"},{"issue":"3","key":"2602_CR18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1177\/1740774510369019","volume":"7","author":"B Freidlin","year":"2010","unstructured":"Freidlin B, Korn EL, Gray R. A general inefficacy interim monitoring rule for randomized clinical trials. Clin Trials. 2010;7(3):197\u2013208.","journal-title":"Clin Trials"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-2602-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-018-2602-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-2602-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T19:28:25Z","timestamp":1555529305000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-018-2602-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,18]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2602"],"URL":"https:\/\/doi.org\/10.1186\/s13063-018-2602-y","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,18]]},"assertion":[{"value":"21 December 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The trial received favourable ethical opinion from East Midlands \u2013 Edgbaston Research Ethics Committee (16\/WM\/0472) and has Health Research Authority (HRA) approval (IRAS 211270). All participants provide written informed consent to participate and are free to withdraw at any time.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"PS receives honoraria and travel expenses from BMS. SD has received support to attend conferences and speaker fees from BMS. GH has received speaker honoraria from BMS, ROCHE, Merck, AZ and Pfizer. NS has received honoraria for ad boards and speaker fees from BMS. All other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"233"}}