NCT05200988

Checkpoint Inhibition and Chemoradiotherapy as Bladder Sparing Treatment in UC

A Phase 2 Clinical Study to Assess Efficacy of Induction Ipilimumab/Nivolumab to Spare the Bladder in Urothelial Bladder Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Urothelial Carcinoma
• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Ipilimumab + nivolumab	Induction with immune checkpoint blockade: ipilimumab 3mg/kg on day 1, pilimumab 3mg/kg plus nivolumab 1mg/kg on day 22, and nivolumab 3mg/kg on day 43 Response evaluation after the last cycle of checkpoint inhibition. Chemoradiation will start 10-12 weeks after start of checkpoint inhibition according to the following scheme: * Mitoycine C (12mg/m2) on the first day of radiotherapy, followed by either 5-fluorouracil intravenously (500mg/m2) five days a week during week one and four of radiation, or oral capecitabin (2x825mg/m2) every day during the radiation period * Radiation with a preference for a four-week schedule, in which 55 Gy will be administered using intensity modulated radiation therapy

Timeline

• Start date: 2022-03-14
• Primary completion: 2025-09-05
• Completion: 2027-09-05
• First posted: 2022-01-21
• Last updated: 2024-03-18

Locations

3 sites across 1 country: Netherlands