Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-19T02:04:11.612Z Has data issue: false hasContentIssue false

Chapter 10 - Case Studies of Platform Trials

from Part IV - Case Studies of Adaptive Trial Designs and Master Protocols

Published online by Cambridge University Press:  20 March 2023

Jay J. H. Park
Affiliation:
McMaster University, Ontario
Edward J. Mills
Affiliation:
McMaster University, Ontario
J. Kyle Wathen
Affiliation:
Cytel, Cambridge, Massachusetts
Get access

Summary

In this chapter, we discuss four adaptive randomised platform trials as case studies. We review two of the longest ongoing platform trials and another two important examples of ongoing platform trials conducted for COVID-19.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Park, JJH, Siden, E, Zoratti, MJ, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572.Google Scholar
Vanderbeek, AM, Bliss, JM, Yin, Z, Yap, C. Implementation of platform trials in the COVID-19 pandemic: a rapid review. Contemp Clin Trials. 2022;112:106625.CrossRefGoogle ScholarPubMed
Parmar, MK, Barthel, FM, Sydes, M, et al. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst. 2008;100(17):1204–14.CrossRefGoogle ScholarPubMed
James, ND, Sydes, MR, Clarke, NW, et al. Systemic therapy for advancing or metastatic prostate cancer (STAMPEDE): a multi-arm, multistage randomized controlled trial. BJU Int. 2009;103(4):464–9.Google Scholar
Sydes, MR, Parmar, MKB, James, ND, et al. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Trials. 2009;10:39.CrossRefGoogle ScholarPubMed
National Library of Medicine. Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE). ClinicalTrials.gov Identifier NCT00268476; 22 December 2005, last updated 13 April 2022. https://clinicaltrials.gov/ct2/show/NCT00268476Google Scholar
James, ND, Sydes, MR, Clarke, NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–77.Google Scholar
Mason, MD, Clarke, NW, James, ND, et al. Adding celecoxib with or without zoledronic acid for hormone-naïve prostate cancer: long-term survival results from an adaptive, multiarm, multistage, platform, randomized controlled trial. J Clin Oncol. 2017;35(14):1530.Google Scholar
James, ND, de Bono, JS, Spears, MR, et al. Abiraterone for Prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338–51.Google Scholar
Parker, CC, James, ND, Brawley, CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353–66.Google Scholar
Attard, G, Murphy, L, Clarke, NW, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022;399(10323):447–60.Google Scholar
James, ND, Spears, MR, Clarke, NW, et al. Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer: data from patients in the control arm of the STAMPEDE trial. JAMA Oncol. 2016;2(3):348–57.Google Scholar
Redman, MW, Allegra, CJ. The master protocol concept. Semin Oncol. 2015;42(5):724–30.Google Scholar
Royston, P, Parmar, MK, Qian, W. Novel designs for multi-arm clinical trials with survival outcomes with an application in ovarian cancer. Stat Med. 2003;22(14):2239–56.Google Scholar
Millen, GC, Yap, C. Adaptive trial designs: what are multiarm, multistage trials? Arch Dis Child Educ Prac. 2020;105(6):376–8.Google Scholar
Park, JJH, Harari, O, Dron, L, et al. An overview of platform trials with a checklist for clinical readers. J Clin Epidemiol. 2020;125:18.Google Scholar
Angus, DC, Alexander, BM, Berry, S, et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797807.Google Scholar
Sydes, MR, James, ND, Mason, MD, et al. Flexible trial design in practice – dropping and adding arms in STAMPEDE: a multi-arm multi-stage randomised controlled trial. Trials. 2011;12(suppl. 1).Google Scholar
Sydes, MR, Parmar, MKB, Mason, MD, et al. Flexible trial design in practice – stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial. Trials. 2012;13:168.Google Scholar
Sweeney, CJ, Chen, YH, Carducci, M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737–46.CrossRefGoogle ScholarPubMed
Gravis, G, Boher, JM, Joly, F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70(2):256–62.Google Scholar
Vale, CL, Burdett, S, Rydzewska, LHM, et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016;17(2):243–56.Google Scholar
Park, JJH, Detry, MA, Murthy, S, Guyatt, G, Mills, EJ. How to use and interpret the results of a platform trial: users’ guide to the medical literature. JAMA. 2022;327(1):6774.Google Scholar
Woodcock, J, LaVange, LM. Master protocols to study multiple therapies, multiple diseases, or both. N Engl J Med. 2017;377(1):6270.CrossRefGoogle ScholarPubMed
Park, JW, Liu, MC, Yee, D, et al. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016;375(1):1122.Google Scholar
Rugo, HS, Olopade, OI, DeMichele, A, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):2334.CrossRefGoogle ScholarPubMed
Barker, AD, Sigman, CC, Kelloff, GJ, et al. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009;86(1):97100.Google Scholar
Mook, S, Van’t Veer, LJ, Rutgers, EJ, Piccart-Gebhart, MJ, Cardoso, F. Individualization of therapy using Mammaprint: from development to the MINDACT trial. Cancer Genomics Proteomics. 2007;4(3):147–55.Google Scholar
Cardoso, F, Van’t Veer, L, Rutgers, E, et al. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol. 2008;26(5):729–35.Google Scholar
National Library of Medicine. I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY). ClinicalTrials.gov Identifier NCT01042379; 5 January 2010; last updated 10 June 2022. https://clinicaltrials.gov/ct2/show/NCT01042379.Google Scholar
Das, S, Lo, AW. Re-inventing drug development: a case study of the I-SPY 2 breast cancer clinical trials program. Contemp Clin Trials. 2017;62:168–74.Google Scholar
Chien, AJ, Tripathy, D, Albain, KS, et al. MK-2206 and standard neoadjuvant chemotherapy improves response in patients with human epidermal growth factor receptor 2–positive and/or hormone receptor–negative breast cancers in the I-SPY 2 trial. J Clin Oncol. 2020;38(10):1059.CrossRefGoogle ScholarPubMed
Nanda, R, Liu, MC, Yau, C, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676–84.Google Scholar
Wise, J, Coombes, R. Covid-19: the inside story of the RECOVERY trial. BMJ. 2020;370:m2670.Google Scholar
The RECOVERY trial. 2020. www.recoverytrial.net/Google Scholar
Park, JJ, Mogg, R, Smith, GE, et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021;9(5):e711–e20.Google Scholar
Park, JJ, Ford, N, Xavier, D, et al. Randomised trials at the level of the individual. Lancet Glob Health. 2021;9(5):e691e700.Google Scholar
Park, JJ, Grais, RF, Taljaard, M, et al. Urgently seeking efficiency and sustainability of clinical trials in global health. Lancet Glob Health. 2021;9(5):e681–e90.Google Scholar
Narhi, F, Moonesinghe, SR, Shenkin, SD, et al. Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study. Lancet Digit Health. 2022;4(4):e220–e34.Google Scholar
Recovery Collaborative Group, Horby, P, Lim, WS, Emberson, JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693704.Google Scholar
RC Group, Horby, P, Lim, WS, Emberson, JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693704.Google Scholar
NIHR. Recruiting patients for clinical trials for COVID-19 Therapeutics; 2020. www.nihr.ac.uk/documents/news/recruiting-patients-for-clinical-trials-for-covid-therapeutics.pdfGoogle Scholar
Horby, P, Lim, WS, Emberson, J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020:2020.06.22.20137273.Google Scholar
RC Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022;399(10325):665–76.Google Scholar
RC Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022;399(10320):143–51.Google Scholar
RC Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med. 2021;9(12):1419–26.Google Scholar
RC Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. 2021;397(10289):2049–59.Google Scholar
RC Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637–45.Google Scholar
RC Group. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10274):605–12.Google Scholar
RC Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396(10259):1345–52.Google Scholar
RC Group, Horby, P, Mafham, M, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383(21):2030–40.Google Scholar
Park, JJH, Dron, L, Mills, EJ. Moving forward in clinical research with master protocols. Contemp Clin Trials. 2021;106:106438.Google Scholar
Forrest, JI, Rawat, A, Duailibe, F, et al. Resilient clinical trial infrastructure in response to the COVID-19 pandemic: lessons learned from the TOGETHER randomized platform clinical trial. Am J Trop Med Hyg. 2022;106(2):389–93.Google Scholar
Reis, G, Moreira Silva, EAdS, Medeiros Silva, DC, et al. Effect of early treatment with hydroxychloroquine or lopinavir and ritonavir on risk of hospitalization among patients with COVID-19: the TOGETHER randomized clinical trial. JAMA Netw Open. 2021;4(4):e216468–e.Google Scholar
Reis, G, Moreira Silva, EAdS, Silva, DCM, et al. A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol. Gates Open Res. 2021;5:117.Google Scholar
Reis, G, Silva, E, Silva, DCM, et al. Effect of early treatment with ivermectin among patients with Covid-19. N Engl J Med. 2022.Google Scholar
Reis, G, Dos Santos Moreira-Silva, EA, Silva, DCM, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health. 2022;10(1):e42e51.Google Scholar
Reis, G, Silva, EAdSM, Silva, DCM, et al. Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: the TOGETHER randomized platform clinical trial. Lancet Regional Health-Americas. 2022;6:100142.Google Scholar
Lee, TC, Vigod, S, Bortolussi-Courval, E, et al. Fluvoxamine for outpatient management of COVID-19 to prevent hospitalization: a systematic review and meta-analysis. JAMA Netw Open. 2022; 5(4):e226269.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×