Checkpoint Inhibition and Chemoradiotherapy as Bladder Sparing Treatment in UC

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, bladder function and long-term effects of immunotherapy on QoL.

Key secondary endpoints are overall survival (OS), recurrence-free survival (RFS), feasibility to proceed to chemoradiation, safety, QoL, and bladder function.