A Phase II Trial of MK3475 in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder Sparing Treatment for Muscle-Invasive Urothelial Cancer of the Bladder

New York University School of Medicine
Study Design: 
This is a single arm, Phase II study for muscle-invasive bladder cancer patients who are not cystectomy candidates or refuse cystectomy. Since the combination has not been evaluated together, there is a safety lead-in cohort of 3-6 patients.
Building on the success of chemoradiotherapy for muscle-invasive bladder cancer and immunotherapy in bladder cancer, this trial combines pembrolizumab with gemcitabine and radiation therapy for muscle-invasive bladder cancer. The hypothesis is that the addition of a checkpoint inhibitor can achieve better local and systemic control of disease.
The primary endpoint is the two-year bladder-intact disease-free survival rate. This is freedom from bladder recurrence, pelvic recurrence, distant metastases, bladder cancer-related death, and cystectomy. Secondary endpoints include the following: safety, complete response rate, overall survival, and metastasis-free survival.
This trial expands on traditional inclusion criteria for chemoradiotherapy by allowing up to T4a tumors to be included and there is no exclusion criteria for associated CIS or hydronephrosis. This is concerning as we know from radiation literature that patients with these adverse pathologic features do not respond as well to chemoradiotherapy. Finally, a complete TURBT is not required for inclusion and this is most concerning as the radical TUR may be a critical part of the bladder-sparing approach. Perhaps the addition of immunotherapy can compensate for these adverse features and possibly expand the role of chemoradiotherapy.