Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial
IntroductionStudies 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. Ch...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1246603/full |
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| author | C.F. Stockem J.J.J. Mellema B.W.G. van Rhijn T.N. Boellaard M.L. van Montfoort S. Balduzzi J.L. Boormans M. Franckena R.P. Meijer D.G.J. Robbrecht B.B.M. Suelmann E.E. Schaake M.S. van der Heijden |
| author_facet | C.F. Stockem J.J.J. Mellema B.W.G. van Rhijn T.N. Boellaard M.L. van Montfoort S. Balduzzi J.L. Boormans M. Franckena R.P. Meijer D.G.J. Robbrecht B.B.M. Suelmann E.E. Schaake M.S. van der Heijden |
| author_sort | C.F. Stockem |
| collection | DOAJ |
| description | IntroductionStudies 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 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.MethodsThe 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.DiscussionThis 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 RegistrationThe INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988). |
| first_indexed | 2024-03-12T12:16:26Z |
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| last_indexed | 2024-03-12T12:16:26Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-2561f22f0c4a47d3a373cdba195158f62023-08-30T10:21:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.12466031246603Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trialC.F. Stockem0J.J.J. Mellema1B.W.G. van Rhijn2T.N. Boellaard3M.L. van Montfoort4S. Balduzzi5J.L. Boormans6M. Franckena7R.P. Meijer8D.G.J. Robbrecht9B.B.M. Suelmann10E.E. Schaake11M.S. van der Heijden12Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Oncological Urology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Radiology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Statistics, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Oncological Urology, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Radiotherapy, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Oncological Urology, University Medical Center (UMC), Utrecht, NetherlandsDepartment of Medical Oncology, Erasmus Medical Center, Rotterdam, Netherlands0Department of Medical Oncology, University Medical Center (UMC), Utrecht, Netherlands1Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, NetherlandsIntroductionStudies 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 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.MethodsThe 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.DiscussionThis 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 RegistrationThe INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).https://www.frontiersin.org/articles/10.3389/fonc.2023.1246603/fullMuscle-invasive bladder cancerbladder preservationimmune checkpoint blockadechemoradiationtrimodal therapy |
| spellingShingle | C.F. Stockem J.J.J. Mellema B.W.G. van Rhijn T.N. Boellaard M.L. van Montfoort S. Balduzzi J.L. Boormans M. Franckena R.P. Meijer D.G.J. Robbrecht B.B.M. Suelmann E.E. Schaake M.S. van der Heijden Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial Frontiers in Oncology Muscle-invasive bladder cancer bladder preservation immune checkpoint blockade chemoradiation trimodal therapy |
| title | Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial |
| title_full | Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial |
| title_fullStr | Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial |
| title_full_unstemmed | Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial |
| title_short | Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial |
| title_sort | induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ sparing treatment in urothelial bladder cancer study protocol of the indiblade trial |
| topic | Muscle-invasive bladder cancer bladder preservation immune checkpoint blockade chemoradiation trimodal therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1246603/full |
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