Surgical Techniques for Bladder Cancer

Recruiting at 6 trial locations

Overseen By Alvin Goh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Opioids

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

530 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two surgical techniques to assess their impact on recovery after bladder cancer surgery. One technique uses a ureteral stent, a tube placed in the ureter to aid urine flow, though it may cause infections. The other technique involves the drug alvimopan (Entereg) to stimulate bowel movement post-surgery. Surgeons will either choose the technique or assign it randomly if uncertain. This trial may suit individuals with bladder cancer scheduled for a radical cystectomy (bladder removal surgery) who are not on long-term opioid medication. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in bladder cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on chronic opioid therapy, you cannot receive alvimopan as part of the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that alvimopan is generally safe for use after surgery. Patients who took alvimopan recovered bowel function faster, allowing them to eat and digest food sooner, which helped them leave the hospital earlier. The safety profile of alvimopan was similar to not taking the drug, as it did not cause more side effects than usual.

For ureteral stents, which are thin tubes used to help urine drain after bladder surgery, safety information is mixed. Some studies suggest that stents can lead to urinary tract infections (UTIs), while others did not find significant issues. However, the type of stent might affect the risk of complications. Specifically, one study found that certain types of stents were linked to fewer infections.

In summary, alvimopan is well-tolerated and aids recovery after surgery. Stents can be safe but may increase the risk of infections depending on the type used. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for bladder cancer surgery because they offer potential improvements in recovery and surgical outcomes. Alvimopan is a medication that can speed up the return of bowel function after surgery by blocking opioid receptors in the gut, which can lead to faster recovery times compared to standard care. On the other hand, the use of ureteral stents, particularly with the flexibility in size and type, may help ensure better urinary drainage and reduce complications, tailored to the surgeon’s expertise and the patient's needs. These innovations could lead to shorter hospital stays and improved patient experiences post-surgery.

What evidence suggests that these surgical techniques are effective for bladder cancer?

In this trial, participants will be randomized to receive either alvimopan or no alvimopan. Research has shown that alvimopan can speed up recovery after bladder cancer surgery. It enables patients to resume eating regular food sooner and shortens hospital stays by helping the digestive system return to normal more quickly post-surgery.

Another part of this trial compares the use of ureteral stents to no stents. The results for ureteral stents are mixed. While they aid in urine drainage, some studies suggest they might increase certain risks, such as additional cancers in the upper urinary tract. The effectiveness of stents depends on each patient's specific needs and risks. ^{5 6 7 8 9}

Who Is on the Research Team?

Alvin Goh, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals undergoing radical cystectomy, a surgery for bladder cancer. Participants must be suitable candidates for the surgical procedure. The study excludes those who have conditions or circumstances that might interfere with the trial procedures or outcomes.

Inclusion Criteria

I am 21 or older and will have surgery for bladder cancer at MSK.

I am 21 or older and will have surgery for bladder cancer at MSK.

Exclusion Criteria

No exclusion criteria Alvimopan vs. no alvimopan

I am not on long-term opioid pain medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Immediate Postoperative Care

Participants undergo radical cystectomy with potential use of ureteral stents and/or alvimopan as per randomization

1 week

In-hospital stay

Postoperative Monitoring

Participants are monitored for length of hospital stay and symptomatic urinary tract infections

4 weeks

In-hospital and follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alvimopan
• Stent placement

Trial Overview The study compares two standard surgical techniques during cystectomy: ureteral stent placement to aid urine drainage and Alvimopan use to speed up bowel function recovery post-surgery. Surgeons may assign these methods by chance if there's uncertainty about which is best.

How Is the Trial Designed?

Group I: Stent vs No Stent Experimental Treatment 1 Intervention

For patients treated by a surgeon randomized to use ureteral stents, the operating surgeon may choose to use a single or double J ureteral stent (6- to 8.5-fr in size) or an alternative ureteral stent of the surgeon's choice to be placed across the ureteroenteric anastomosis intraoperatively. Because there is no standard ureteral stent size or type, the surgeon will select a stent type and size according to their experience and will document the stent size and type used. This is already routinely recorded as part of the standard of care at MSK.

Group II: Alvimopan vs No Alvimopan Experimental Treatment 1 Intervention

For patients randomized to receive alvimopan, the patient will receive alvimopan as a fixed 12-mg dose, with the first dose administered 0.5 to 5 h before the start of surgery; administration will be continued with twice daily oral doses postoperatively until hospital discharge or a maximum of 7 days (15 in-hospital doses), as indicated on the medication's FDA label. This is the current standard of care for most cases at MSK.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The endoscopic placement of the Gibbons indwelling stent in obstructed ureters is safer and associated with lower morbidity and mortality compared to traditional methods like supravesical diversion, making it a better option for high-risk patients.

In a study involving 16 patients aged 25 to 74, the Gibbons stent not only preserves quality of life better than other methods but is also reversible and does not interfere with future surgeries, although some technical challenges may arise during placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ureteral drainage with the Gibbons indwelling ureteral stent (author's transl)]. Schreiber, B.[2006]

The study introduces a new transurethral stent placement technique during robot-assisted radical prostatectomy (RARP) to prevent ureteral damage, especially in patients with large median lobes or prior surgeries.

This technique is presented as a simple and feasible alternative to preoperative stenting, addressing potential anatomical challenges encountered during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is ureteral stent placement by the transurethral approach during robot-assisted radical prostatectomy an effective option to preoperative technique? Molinari, A., Simonelli, G., De Concilio, B., et al.[2016]

In a study of 573 patients undergoing radical cystectomy, alvimopan significantly improved recovery outcomes for those who had open radical cystectomy (ORC), reducing postoperative ileus rates and hospital length of stay.

However, in patients undergoing robot-assisted radical cystectomy (RARC), alvimopan did not show any significant benefits for recovery, suggesting that its use may need to be more selective based on the surgical approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy. Faraj, KS., Judge, NZ., Rose, KM., et al.[2022]

Routine placement of stents after uncomplicated ureteroscopy is no longer considered necessary, as it leads to increased pain and irritative voiding symptoms for patients.

While stents add to the overall cost of the procedure, there is a specific subgroup of patients who may still benefit from them, indicated by higher readmission rates, suggesting a need for future research to identify these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stenting after ureteroscopy: pros and cons. Knudsen, BE., Beiko, DT., Denstedt, JD.[2014]

The study estimates that using alvimopan for all patients undergoing radical cystectomy can lead to cost savings by reducing the costs associated with postoperative ileus (POI), especially if POI occurs in more than 14% of patients or leads to an extended hospital stay of 3.5 days or more.

Routine administration of alvimopan, which costs $700 per hospitalization, is associated with a lower mean cost of $1495 per patient for POI management, compared to $1597 for patients not treated with the drug, indicating its potential cost-effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alvimopan for prevention of postoperative paralytic ileus in radical cystectomy patients: a cost-effectiveness analysis. Hilton, WM., Lotan, Y., Parekh, DJ., et al.[2022]

Endoscopically placed ureteral stents are a safe and effective method for managing ureteral obstruction and can improve the quality of life for high-risk patients with malignancies without the need for surgery.

The technique described allows for customized stent fitting using readily available graduated ureteral catheters, minimizing preparation time and eliminating the need for a wide range of catheter sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Useful technique for long-term urinary drainage by inlying ureteral stent. Six-year experience. Kearney, GP., Mahoney, EM., Brown, HP.[2019]

Alvimopan significantly accelerates gastrointestinal recovery in patients undergoing radical cystectomy, as evidenced by faster toleration of clear liquids, solid food, and bowel movements, based on a meta-analysis of 5 studies involving 613 patients.

The use of alvimopan also reduces the length of hospital stay for these patients, indicating its potential to improve postoperative recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alvimopan on accelerates gastrointestinal recovery after radical cystectomy: A systematic review and meta-analysis. Cui, Y., Chen, H., Qi, L., et al.[2018]

In patients undergoing radical cystectomy, alvimopan significantly reduced the time to reach solid food tolerance and hospital discharge, with moderate-quality evidence showing a hazard ratio of 1.77 for food tolerance and 1.67 for discharge, indicating faster recovery compared to standard care.

Alvimopan was associated with a lower risk of major adverse events (risk ratio 0.28), suggesting it may enhance safety during recovery, while not affecting readmission rates or narcotic pain medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alvimopan for recovery of bowel function after radical cystectomy. Sultan, S., Coles, B., Dahm, P.[2023]

Ureteral stenting in patients with bladder cancer significantly increases the risk of developing metachronous upper tract urothelial carcinoma, with a likelihood 3.49 times higher compared to those with no stents.

In cases of hydronephrosis, both nephrostomy and ureteral stenting are viable drainage options, as they do not differ in their risk of metachronous upper tract urothelial carcinoma, suggesting that stenting should be avoided when possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis. Sountoulides, P., Pyrgidis, N., Brookman-May, S., et al.[2021]

The migration of indwelling ureteral stents out of the bladder presents a significant challenge for urologists, often requiring innovative solutions to avoid invasive surgery.

A new transurethral technique has been successfully employed to remove a migrated catheter, potentially offering a less invasive option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transurethral removal of migrated indwelling ureteral stents: a new technique. Berman, D., Donovan, J., Assimos, D., et al.[2019]

The newly designed 'Yoticurl' stent showed promising results in a preliminary in vivo evaluation in a pig model, demonstrating normal urine flow and no significant complications over a 25-day period.

Histological analysis revealed only mild inflammation in the ureter, suggesting that this innovative stent design may be a safer and more effective alternative to traditional ureteral stents for facilitating urine drainage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a fully intraureteral stent and proof-of-concept in vivo evaluation. Shilo, Y., Willenz, U., Berkowitz, B.[2022]

In a study of 60 patients with double-J ureteral stents, tamsulosin therapy significantly reduced various measures of stent-related discomfort, including pain and urinary symptoms, compared to a placebo after 4 weeks.

Tamsulosin was well tolerated with no reported discontinuations due to side effects, suggesting it is a safe and effective option to minimize morbidity associated with ureteral stenting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tamsulosin hydrochloride in relieving "double-J ureteral stent-related morbidity": a randomized placebo controlled clinical study. Singh, I., Tripathy, S., Agrawal, V.[2021]

In a systematic review of 14 randomized clinical trials involving 2,842 patients, alpha antagonists, antimuscarinics, and phosphodiesterase (PDE) inhibitors were all found to significantly reduce symptoms related to ureteric stents compared to placebo.

Combination therapy using both alpha antagonists and antimuscarinics was more effective in improving symptoms than using either drug alone, while PDE inhibitors showed comparable effectiveness to alpha antagonists and provided additional benefits for sexual health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Ureteral Stent-Related Symptoms. Pecoraro, A., Peretti, D., Tian, Z., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6511706/

Alvimopan for post-radical cystectomy ileus: what should ... Meta-analysis revealed reduced time to toleration of liquid and solid foods, first bowel movement and length of stay in patients who had received alvimopan. As ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/iju.14546

Alvimopan as part of the Enhanced Recovery After Surgery ... The primary outcome was the length of hospital stay. Secondary outcomes were time to first bowel movement, time to tolerate a regular diet, the ...

3. auajournals.org auajournals.org/doi/abs/10.1097/UPJ.0000000000000332

Naloxegol versus Alvimopan for Enhancing Postoperative ... Conclusions: In patients undergoing RC managed with a standard ERAS pathway, there were no differences in postoperative recovery based on the ...

4. journals.sagepub.com journals.sagepub.com/doi/10.3233/BLC-150017

Alvimopan in an Enhanced Recovery Program Following ... Alvimopan was associated with a reduction in mean time to regular diet (5.3 vs 4.1 days, p < 0.01) and a reduction in mean length of hospital ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1743919115013291

Effect of alvimopan on accelerates gastrointestinal ... This meta-analysis has shown that alvimopan significantly accelerates recovery of gastrointestinal function and reduces the length of stay in patients ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24630419/

Alvimopan accelerates gastrointestinal recovery after ... Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03216525?term=ALVIMOPAN%20ANHYDROUS&rank=8

Study Details | NCT03216525 | Alvimopan Versus Placebo ... A prospective, randomized, single-center double blind trial of Alvimopan versus placebo for improving patient outcomes and cost during radical cystectomy and ...

8. jdc.jefferson.edu jdc.jefferson.edu/cgi/viewcontent.cgi?article=1131&context=patientsafetyposters

Cystectomy Safety Presentation - Jefferson Digital Commons ... Alvimopan data). • Thirty-seven of fifty (74%) received Alvimopan per protocol. • Median post-operative LOS for patients receiving Alvimopan was 7 days with 30%.

9. nature.com nature.com/articles/nrurol.2014.67

Faster recovery after radical cystectomy with alvimopan Patients who received alvimopan experienced quicker gastrointestinal recovery—a two-component end point combining first tolerance of food and ...