Status:
Closed
Clinicaltrials.gov identifier:
Sponsor:
UroGen Pharma Ltd.
Enrollment:
71
Study Design:
This was a prospective, multicenter open-label single-arm trial evaluating the safety, efficacy, and tolerability of MitoGel instilled into the upper urinary tract of patients with non-invasive low-grade (LG) UTUC. Patients had to have at least one measurable papillary tumor. Patients were treated once weekly for 6 weeks by retrograde instillation. Safety and Efficacy was evaluated approximately 5 weeks following the last instillation, roughly 11 weeks after enrollment, by direct inspection of the upper tract, biopsies of any tumors, and upper tract washed urine cytology. Patients who achieved a CR at 3 months were treated with monthly maintenance therapy for a total of 11 instillations or up to the first recurrence whichever came first.
Rationale:
Unlike bladder urothelial carcinoma, upper tract urothelial carcinoma (UTUC) has not been successfully treated with instillation therapy with chemotherapy or immunotherapy. Although some case reports describe instillation therapy into the upper urinary tract delivered through nephrostomy tubes, there has not been a reliable and convenient method of delivery until now. This trial uses a novel formulation of mitomycin C (MitoGel, now named JELMYTO) that can be instilled in a liquid form which can solidify at body temperature into a gel that can allow dwell times of several hours in the upper urinary tract. Mitomycin C is an alkylating agent that inhibits the transcription of DNA into RNA thereby preventing protein synthesis and inhibiting growth of cancer cells. It has shown to be effective in urothelial cancer of the bladder.
Endpoints:
The primary endpoint was the complete response (CR) rate at 3 months. Secondary endpoints included the CR rate at 12 months. The mitomycin C level was also evaluated in the plasma of a subgroup of the patients.
Comments:
This is the first trial exclusively for upper tract urothelial cancer and it establishes the first FDA-approved therapy in this rare, “orphan,” disease. In addition, the therapy was effective in patients without complete resection/ablation of existing papillary tumors. However, the response rate was only durable at 12 months in approximately 20% (14 of 71) of the patients and was limited to only those patients with LG disease. Given the inaccuracies with grading and staging of upper tract urothelial cancer based on small volume biopsies, it is also conceivable that some patients with high grade disease may be inadvertently treated with this approach which may not be effective. Nevertheless, this trial has paved the way for localized therapies for UTUC.
Results:
This study demonstrated a CR rate of 59% (42 patients) at 3 months. Nineteen of these patients (46%) maintained a CR at 12 months. The most frequent adverse events included ureteric stenosis (44%), urinary tract infection (32%), hematuria (31%), flank pain (30%), and nausea (24%). Of note, of the patients who developed ureteric obstruction, 51% had some level of persistent obstruction.
