This is a phase 2 study in which fifty adult patients with cT2-4aN0-2 urothelial bladder cancer, who are amenable for chemoradiation, will be included. Lymph nodes should be amenable for inclusion into the radiation field.~Included patients will be treated with three cycles of checkpoint inhibition: ipilimumab 3mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43.~Response of this induction therapy will be evaluated by cystoscopy, mpMRI and a CT scan.~Patients will then be treated by radiation to the bladder and involved nodes, in combination with mitomycine C (day 1, 12 mg/m2, maximum dose of 20 mg) and either daily capecitabin or intravenous 5-FU in week 1 and 4. Radiotherapy will be delivered using Volumetric Modulated Arc Therapy delivering a dose of 50Gy to the whole bladder with a simultaneous tumor boost of 60Gy to the tumor bed.~The primary endpoint is efficacy, defined as bladder-intact event-free survival (BI-EFS). Events consist of death by any cause; muscle-invasive, upper urinary tract, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.~The first evaluation after completion of chemoradiation will be after three months. Further follow-up visits will take place 6, 12, 18, 24, 30, and 36 months after completion of chemoradiation. During these visits, focused physical examination, cystoscopy and a CT chest-abdomen will be performed, combined with registration of treatment-related adverse events and a questionnaire for evaluating QoL and bladder function.~Key secondary endpoints are overall survival (OS), recurrence-free survival (RFS), feasibility to proceed to chemoradiation, safety, QoL, and bladder function.
This is a single-armed, multicenter, non-blinded phase 2 study to assess efficacy of induction ipilimumab + nivolumab followed by chemoradiation to spare the bladder in urothelial bladder cancer.