Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial
Stockem, C. F.; Mellema, J. J.J.; van Rhijn, B. W.G.; Boellaard, T. N.; van Montfoort, M. L.; Balduzzi, S.; Boormans, J. L.; Franckena, M.; Meijer, R. P.; Robbrecht, D. G.J.; Suelmann, B. B.M.; Schaake, E. E.; van der Heijden, M. S.
(2023) Frontiers in oncology, volume 13
(Article)
Abstract
Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar
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oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).
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Keywords: bladder preservation, chemoradiation, immune checkpoint blockade, Muscle-invasive bladder cancer, trimodal therapy, Oncology, Cancer Research
ISSN: 2234-943X
Publisher: Frontiers Media S. A.
Note: Funding Information: The INDIBLADE trial is funded by Bristol Myers Squibb and the Dutch Cancer Society (KWF grant 13226). Acknowledgments Publisher Copyright: Copyright © 2023 Stockem, Mellema, van Rhijn, Boellaard, van Montfoort, Balduzzi, Boormans, Franckena, Meijer, Robbrecht, Suelmann, Schaake and van der Heijden.
(Peer reviewed)