Understanding Clinical Trials in Malignant Mesothelioma

  • Aaron MansfieldEmail author
  • Dennis WigleEmail author
  • Tobias PeikertEmail author


Clinical trials are essential to improving outcomes for patients with mesothelioma. There are many phases of drug development that are necessary for the stepwise testing of novel therapeutics. Additionally, novel technologies that are used to screen for mutations or detect biomarkers have changed the clinical trial landscape significantly over the last few years. In the chapter that follows, we describe the basics of the drug development process to help patients and their caregivers make informed decisions about participation in clinical trials and other research opportunities.


  1. Department of Health and Human Services Food and Drug Administration. Individual patient expanded access investigational new drug application (IND).Google Scholar
  2. 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;18:623–30. Scholar
  3. Batirel HF, et al. Adoption of pleurectomy and decortication for malignant mesothelioma leads to similar survival as extrapleural pneumonectomy. J Thorac Cardiovasc Surg. 2016;151:478–84. Scholar
  4. Bovolato P, et al. Does surgery improve survival of patients with malignant pleural mesothelioma?: a multicenter retrospective analysis of 1365 consecutive patients. J Thorac Oncol. 2014;9:390–6. Scholar
  5. Bryce AH, et al. Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery. Oncotarget. 2017;8:27145–54. Scholar
  6. Burt BM, et al. Malignant pleural mesothelioma and the Society of Thoracic Surgeons Database: an analysis of surgical morbidity and mortality. J Thorac Cardiovasc Surg. 2014;148:30–5. Scholar
  7. Byrne M. J., Nowak A. K., Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004;15:257–60. Scholar
  8. Cao C, et al. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer. 2014;83:240–5. Scholar
  9. Caplan AL, Bateman-House A, Waldstreicher J. Compassionate use: a modest proposal. Am Soc Clin Oncol Educ Book. 2016;35:e2–4. Scholar
  10. Chan WH, Sugarbaker DJ, Burt BM. Intraoperative adjuncts for malignant pleural mesothelioma. Transl Lung Cancer Res. 2017;6:285–94. Scholar
  11. de Perrot M, et al. Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2016;151:468–73. Scholar
  12. Ettinger DS, et al. NCCN guidelines insights: malignant pleural mesothelioma, version 3.2016. J Natl Compr Cancer Netw. 2016;14:825–36.CrossRefGoogle Scholar
  13. Flores RM, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135:620–6, 626 e621–623. Scholar
  14. Friedberg JS, et al. Extended pleurectomy-decortication-based treatment for advanced stage epithelial mesothelioma yielding a median survival of nearly three years. Ann Thorac Surg. 2017;103:912–9. Scholar
  15. Gill RR, et al. Epithelial malignant pleural mesothelioma after extrapleural pneumonectomy: stratification of survival with CT-derived tumor volume. AJR Am J Roentgenol. 2012;198:359–63. Scholar
  16. Hassan R, et al. Mesothelin immunotherapy for cancer: ready for prime time? J Clin Oncol. 2016;34:4171–9. Scholar
  17. Hedy L, Kindler NI, Armato SG III, Bueno R, Hesdorffer M, Jahan T, Jones CM, Miettinen M, Pass H, Rimner A, Rusch V, Sterman D, Thomas A, Hassan R. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(13):1343–73.Google Scholar
  18. Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010;16:1726–36. Scholar
  19. Levin PA, Dowell JE. Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date. Onco Targets Ther. 2017;10:2057–66. Scholar
  20. LoRusso PM, Boerner SA, Seymour L. An overview of the optimal planning, design, and conduct of phase I studies of new therapeutics. Clin Cancer Res. 2010;16:1710–8. Scholar
  21. Mailankody S, Prasad V. Thinking systematically about the off-label use of cancer drugs and combinations for patients who have exhausted proven therapies. Oncologist. 2016;21:1031–2. Scholar
  22. Mansfield AS. Immune checkpoint inhibition in malignant mesothelioma: does it have a future? Lung Cancer. 2017;105:49–51. Scholar
  23. Mansfield AS, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9:1036–40. Scholar
  24. Mansfield AS, et al. Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib. Ann Oncol. 2016;27:2111–7. Scholar
  25. Mansfield A, Peikert T, Vogelzang N, Symanowski J. Effects of tumor burden reduction on survival in epithelioid pleural mesothelioma. J Thorac Oncol. 2017;12Google Scholar
  26. Mansfield A, Peikert T, Vogelzang N, Symanowski J. Effects of tumor burden reduction on survival in epithelioid pleural mesothelioma. Mayo Clin Proc. 2018;93(8):1026–33. Epub 2018 May 24CrossRefGoogle Scholar
  27. Marulli G, et al. Pleurectomy-decortication in malignant pleural mesothelioma: are different surgical techniques associated with different outcomes? Results from a multicentre study. Eur J Cardiothorac Surg. 2017;52:63–9. Scholar
  28. Paoletti X, Drubay D, Collette L. Dose-finding methods: moving away from the 3 + 3 to include richer outcomes. Clin Cancer Res. 2017;23:3977–9. Scholar
  29. Prasad V. Double-crossed: why crossover in clinical trials may be distorting medical science. J Natl Compr Cancer Netw. 2013;11:625–7.CrossRefGoogle Scholar
  30. Renfro LA, Sargent DJ. Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples. Ann Oncol. 2017;28:34–43. Scholar
  31. Rimner A, et al. Phase II study of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) as part of lung-sparing multimodality therapy in patients with malignant pleural mesothelioma. J Clin Oncol. 2016;34:2761–8. Scholar
  32. Rusch VW, et al. A multicenter study of volumetric computed tomography for staging malignant pleural mesothelioma. Ann Thorac Surg. 2016;102:1059–66. Scholar
  33. Scagliotti GV, et al. LUME-Meso: design and rationale of the phase III part of a placebo-controlled study of nintedanib and pemetrexed/cisplatin followed by maintenance nintedanib in patients with unresectable malignant pleural mesothelioma. Clin Lung Cancer. 2017;18:589–93. Scholar
  34. Schwartz RM, Watson A, Wolf A, Flores R, Taioli E. The impact of surgical approach on quality of life for pleural malignant mesothelioma. Ann Transl Med. 2017;5:230. Scholar
  35. Seymour L, et al. The design of phase II clinical trials testing cancer therapeutics: consensus recommendations from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010;16:1764–9. Scholar
  36. Shaikh F, et al. Improved outcomes with modern lung-sparing trimodality therapy in patients with malignant pleural mesothelioma. J Thorac Oncol. 2017;12:993–1000. Scholar
  37. Simon R. Critical review of umbrella, basket, and platform designs for oncology clinical trials. Clin Pharmacol Ther. 2017;102:934–41. Scholar
  38. Taioli E, Wolf AS, Flores RM. Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg. 2015;99:472–80. Scholar
  39. Treasure T, et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol. 2011;12:763–72. Scholar
  40. Trialists M, Lim E. Surgical selection in pleurectomy decortication for mesothelioma – an overview from screening and selection from MARS 2 pilot. J Thorac Oncol. 2017;12:S1748.CrossRefGoogle Scholar
  41. Verma V, et al. National cancer database report on pneumonectomy versus lung-sparing surgery for malignant pleural mesothelioma. J Thorac Oncol. 2017;12:1704–14. Scholar
  42. 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;21:2636–44. Scholar
  43. West HJ. Novel precision medicine trial designs: umbrellas and baskets. JAMA Oncol. 2017;3:423. Scholar
  44. Wolchok JD, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20. Scholar
  45. Woodcock J, LaVange LM. Master protocols to study multiple therapies, multiple diseases, or both. N Engl J Med. 2017;377:62–70. Scholar
  46. 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;387:1405–14. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Mayo ClinicRochesterUSA

Personalised recommendations