Ignite Creation Date:
2024-05-06 @ 4:05 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04865939
Status:
RECRUITING
Last Update Posted:
2023-12-07
First Post:
2021-04-26
Brief Title:
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
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
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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 108 and 144 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 eg 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 471 and 526 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 758 662 and 632 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 7770 -8100 sterile water 74 IQR 633-749 saline 767 IQR 760 777 p 021 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
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 108 and 144 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 eg 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 471 and 526 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 758 662 and 632 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 7770 -8100 sterile water 74 IQR 633-749 saline 767 IQR 760 777 p 021 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None