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Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Carcinoma, Transitional Cell

Urologic Neoplasms

Urogenital Neoplasms

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

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Transitional Cell Carcinoma

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All Drugs and Chemicals

Anti-Infective Agents

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Antibiotics, Antitubercular

Mitomycins

Mitomycin

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Alkylating Agents

The dose of Jelmyto to be instilled is 4 mg per mL via ureteral catheter or a nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not to exceed 15 mL (60 mg of mitomycin).

Instill Jelmyto once weekly for six weeks. For patients with a complete response 3 months after Jelmyto initiation, Jelmyto instillations may be administered once a month for a maximum of 11 additional instillations.

Jelmyto (mitomycin) for pyelocalyceal solution

Anthony Fernandez, PharmD

Brett Johnson, MD

Yair Lotan, MD

The purpose of this registry is to evaluate real world experience and outcomes of patients with Upper Tract Urothelial Cancer (UTUC) treated with Jelmyto in the United States.

Patients may be enrolled prospectively, at the time of receiving Jelmyto, or after receiving Jelmyto for retrospective data capture and prospective follow up. Patients will be followed until 3 years after the first dose of Jelmyto or death.

Data will be captured to address specific clinical questions and data gaps related to real world use of Jelmyto.

Example clinical questions:

1. How is Jelmyto used in the real world setting?
2. What adverse events (AEs) and at what rates and time points are they observed in the real world setting?
3. What is the disease volume before and after resection/ablation prior to treating with Jelmyto?
4. Did the use of Jelmyto impact clinical decision making and management?
5. What is the complete response (CR) rate, duration of response, and rate of progression, including subgroups of interest?
6. What are the rates of, time to, and pathology at radical nephroureterectomy (RNU) by response to treatment and number of Jelmyto doses received?
7. What are outcomes for non-responders or partial responders? What are the rates of surgical and therapeutic treatment options received following response assessment, including additional Jelmyto?
8. What was the outcome of patients with solitary kidney and/or chronic kidney disease (CKD)? Did Jelmyto prevent dialysis by avoiding nephrectomy in solitary kidney or in patients with baseline CKD?
9. What is the rate and timing of bladder cancer occurrence and/or recurrences?

uTRACT Jelmyto Registry: A Registry of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto

uTRACT Jelmyto Registry: A Multicenter, Prospective and Retrospective Registry to Evaluate Real World Experience and Outcomes of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto

UroGen Pharma Ltd.

Urinary Bladder Neoplasms

Infertility

Gemcitabine

Antimetabolites

intravesical instillation of gemcitabine (1 g in 50 mL saline) with dwell time of 1 - 3 hours

intravesical continuous bladder irrigation with sterile water for 1 - 3 hours and a total instilled volume of approximately 4 - 16 liters

Continuous irrigation of bladder with sterile water during surgery (prior to entry into bladder).

sterile water irrigation

Intravesical gemcitabine instilled into bladder during surgery (drained prior to entry into bladder).

Vitaly Margulis, MD

Aditya Bagrodia, MD

Jeffrey M Howard, MD, PhD

Xiaosong Meng, MD, PhD

Solomon L Woldu, MD

There is a high rate of intravesical (bladder) recurrence following extirpative surgery for upper tract urothelial carcinoma. There is no single established standard of care for prevention of intravesical recurrence; however, one protocol in common use involves the use of intravesical gemcitabine instilled into the bladder during surgery and prior to entry into the bladder. There are barriers to the use of gemcitabine, especially at lower volume centers. Some evidence suggests that intravesical irrigation with sterile water has equivalent efficacy to intravesical chemotherapy in prevention of recurrent bladder cancer following transurethral resection of bladder tumors (TURBT). This study is intended to compare recurrence rates using intravesical gemcitabine (as a pseudo-standard of care) and continuous bladder irrigation with sterile water.

Upper tract urothelial carcinoma is a relatively rare disease, accounting for 5-10% of urothelial malignancies. Following radical nephroureterectomy (RNU), recurrence of urothelial carcinoma in the bladder (UCB) is reported in up to 50% of cases. Although the mechanism of bladder cancer recurrence following RNU is still controversial, recent evidence suggest that these tumors have similar clonal origin to upper tract tumors, supporting the theory of downstream seeding; specifically, that manipulation of the upper tract during surgery results in shedding of tumor cells which then implant in the bladder and give rise to bladder tumors.

Different strategies have been suggested to reduce UCB recurrence rates following RNU. Early clipping of the ureter distal to the tumor may prevent seeding and reduce UCB recurrence, while the correct technique for bladder cuff resection remains debatable. A single, post-operative, prophylactic intravesical chemotherapy instillation (pIVC) has been shown to reduce recurrence rates following resection of UCB. Specifically, two prospective studies have evaluated the use of pIVC using mitomycin-C (MMC) or pirarubicin (THP) following RNU, showing a 11-25% absolute reduction in the risk of UCB recurrence. The safety of pIVC has previously been reported by Moriarty et al. with no directly associated adverse events. The investigators' group also compared bladder recurrence rates in patients who received intraoperative or postoperative pIVC. In this cohort, 12- and 24-month recurrence rates in the I-pIVC groups were 10.8% and 14.4%, respectively, with a favorable safety profile. Current practice at this institution, which is widely employed at many centers but is not supported by Level I evidence, is to instill gemcitabine into the bladder intraoperatively and to allow it to dwell within the bladder until excision of the ureter, at which time the gemcitabine is drained prior to entry into the bladder.

Despite its demonstrated benefits, there appears to be considerable underutilization of pIVC for various reasons. Based on a national survey in the United States, less than 50% of urologic oncologists use pIVC, mainly due to concerns including lack of evidence, fear of extravasation and office infrastructure. While educational measures should be taken to increase urologists' awareness of the importance and high level evidence supporting the use of pIVC, other concerns, such as extravasation and logistical issues (which may include office infrastructure, availability of chemotherapeutic agents outside of a hospital setting, availability of trained personnel, etc.).

A possible alternative to pIVC that would circumvent logistical, availability-, and toxicity-based concerns is the use of intravesical continuous bladder irrigation (CBI) with sterile water. In this method, a multi-way urinary catheter is placed in the bladder which allows water to be irrigated into the bladder while simultaneously and freely draining out via a separate lumen, allowing the bladder to be continuously irrigated with sterile fluid. In this setting, irrigation would be initiated at the start of the surgical procedure and would be terminated and the bladder drained immediately prior to entry into the bladder at the time of excision of the distal ureter. There have been several studies that have demonstrated the ability of hypotonic fluid (e.g., sterile water) to kill bladder tumor cells. Distilled water irrigation has shown to delay tumor recurrence of bladder cancer by osmolysis of tumor cells. A prospective, randomized, open-label, two-arm, single-center, pilot study compared continuous sterile water irrigation to a single dose intravesical of mitomycin C after transurethral resection of bladder tumors (TURBT) and found recurrence-free rates for MMC and continuous sterile water irrigation groups were 47.1% and 52.6%, respectively. Another study investigated the results of bladder irrigation with water for injection after TURBT. A total of 239 patients (158 with single tumors, group A, and 81 with multiple tumors, group B) received continuous intravesical postoperative irrigation with water. Recurrence-free rate for those patients who received only intravesical irrigation with water was 75.8%, 66.2% and 63.2% at the 1st, 2nd and 3rd year of follow up, respectively. A systemic review of the literature evaluated bladder irrigation after TURBT. There were 6 studies, including 1515 patients of which 361 had saline irrigation and 463 had sterile water. There was no significant difference between IVT chemotherapy, saline and sterile water groups regarding to the median RFS at 1 year \[IVT: 81%, IQR (77.70, -81.00), sterile water: 74%, IQR (63.3-74.9), saline: 76.7% IQR (76.0, 77.7), p = 0.21\]. Adverse events were more frequent amongst patients in the IVT chemotherapy group in comparison to the saline or water groups.

In this study, it is hypothesized that intraoperative continuous bladder irrigation with sterile water is noninferior to intravesical instillation of gemcitabine. If the two regimens are substantially equivalent, irrigation with water would be considered a superior option due to greater simplicity, wider availability, and reduced risk of toxic exposure to the patient and operating room staff.

randomized, single-blinded controlled noninferiority trial

Participants will not be informed of group allocation. Blinding treating clinicians is impractical due to the techniques used.

Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma

A Randomized Trial Comparing Intravesical Gemcitabine to Continuous Bladder Irrigation With Sterile Water to Prevent Bladder Cancer Implantation in Patients Undergoing Excision of Upper Tract Urothelial Carcinoma

rate of biopsy proven intravesical recurrence of urothelial carcinoma

University of Texas Southwestern Medical Center

Professor and Chief of Urologic Oncology

Mitomycin for pyelocalyceal solution

Michael Louie, MD, MPH, MSC

This program provides controlled, pre-approval access to JELMYTO in response to unsolicited requests by physicians, hospitals, pharmacies, distributors, ministries of health or other parties on behalf of specific, or named patients, in select countries where JELMYTO has not yet received a marketing authorization and in situations when patients have exhausted all available treatment options.

Named Patient Program for Mitomycin for Pyelocalyceal Solution

Tanner Pharma Group

Mitomycin (40 mg in 40 mL of sterile water) will be administered through a Foley catheter, which will be clamped for two hours.

Mitomycin C

Piotr Zareba, MD MPH

The objective of this pilot study is to determine the feasibility of conducting a phase III randomized trial of intravesical mitomycin C (MMC) for prevention of intravesical recurrence (IVR) after diagnostic ureteroscopy for suspected upper tract urothelial carcinoma (UTUC). In the current study, 40 patients will be randomized to receive MMC or no intervention and will be followed for two years to determine the incidence of adverse events and IVR.

Intravesical Mitomycin C After Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma

Preventing Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract: a Pilot Randomized Trial of a Single Prophylactic Bladder Instillation of Mitomycin C After Diagnostic Ureteroscopy

Proportion of patients who consent to participate in the study after being invited to do so

Proportion of consented patients who are deemed eligible to participate and are randomly allocated to one of the two arms

Proportion of randomized patients who complete follow-up

Cumulative incidence of grade 3-5 adverse events

Cumulative incidence of urothelial carcinoma of the bladder

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
uTRACT Jelmyto Registry: A Registry of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto	NCT05874921	Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Canc... Urothelial Carc... Carcinoma, Tran... Transitional Ce...	Jelmyto (mitomy...	18 Years -	UroGen Pharma Ltd.
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma	NCT04865939	Urothelial Canc... Urothelial Carc...	sterile water i... Gemcitabine	18 Years - 90 Years	University of Texas Southwestern Medical Center
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma	NCT04865939	Urothelial Canc... Urothelial Carc...	sterile water i... Gemcitabine	18 Years - 90 Years	University of Texas Southwestern Medical Center
Named Patient Program for Mitomycin for Pyelocalyceal Solution	NCT05494411	Urothelial Canc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc...	Mitomycin for p...	18 Years -	UroGen Pharma Ltd.
Intravesical Mitomycin C After Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma	NCT05979909	Urothelial Carc... Urothelial Canc...	Mitomycin C	18 Years -	McMaster University
Named Patient Program for Mitomycin for Pyelocalyceal Solution	NCT05494411	Urothelial Canc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc...	Mitomycin for p...	18 Years -	UroGen Pharma Ltd.

Spots Global Cancer Trial Database for urothelial carcinoma ureter