Gemcitabine for the Prevention of Intravesical Recurrence of Urothelial Cancer in Patients With Upper Urinary Tract Urothelial Cancer Undergoing Radical Nephroureterectomy, GEMINI Study
Study Details
Study Description
Brief Summary
This phase II trial studies how well gemcitabine works in preventing urothelial cancer from coming back within the bladder (intravesical recurrence) in patients with upper urinary tract urothelial cancer undergoing radical nephroureterectomy. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Instilling gemcitabine into the bladder during surgery, may reduce the chance of recurrence of upper urinary tract urothelial cancer.
Detailed Description
PRIMARY OBJECTIVE:
- To determine the efficacy of a single intraoperative intravesical instillation of gemcitabine hydrochloride (gemcitabine) at time of radical nephroureterectomy (RNU) for clinically localized upper tract urothelial carcinoma (UTUC) in preventing intravesical recurrence of urothelial cancer (UC) at one year.
SECONDARY OBJECTIVES:
- To assess time to recurrence for entire duration of follow-up. II. To assess the qualitative and quantitative toxicities.
EXPLORATORY OBJECTIVES:
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To stratify intravesical UC recurrence free survival by tumor grade, neoadjuvant chemotherapy, tumor stage, ureteral tumor location, and history of bladder cancer.
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To assess incidence and time to development of muscle-invasive bladder cancer (MIBC).
OUTLINE:
Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU.
After completion of study, patients are followed up at 2 weeks, and 3, 6, 12, 18, and 24 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Prevention (gemcitabine hydrochloride) Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU. |
Drug: Gemcitabine Hydrochloride
Given intravesically
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Relapse-free survival [At 1 year]
Relapse-free survival will be assessed by cystoscopy and urine cytology at 3, 6, 12, 18, and 24 months. Will be evaluated utilizing a one-sided exact test of proportions with alpha level 0.05.
Secondary Outcome Measures
- Time to recurrence [Up to 2 years]
- Incidence of adverse events [Up to 2 years]
Adverse events will be categorized by grade and further distinguished as serious adverse events. Furthermore, they will be designated by each site as not related, unlikely, possible, probably, and definitely related to treatment adverse events. they will also be summarized and organized by organ system, with the number and percent of patients experiencing the adverse event at least once and the number of patients exposed. Adverse events will be described and analyzed qualitatively. Adverse events will be grouped into categories and numerically described.
Other Outcome Measures
- Relapse-free survival [At 2 years]
Overall time-to-recurrence will be assessed through 2 year follow up using survival analysis methods. Will be stratified by tumor grade, neoadjuvant chemotherapy, tumor stage, ureteral tumor location, and history of bladder cancer.
- Incidence of muscle-invasive bladder cancer [Up to 2 years]
Kaplan-Meier estimates will describe estimated event rates at 2 years.
- Time to development of muscle-invasive bladder cancer [From date of radical nephroureterectomy to date of histologic proof of T2 urothelial cancer, assessed up to 2 years]
Kaplan-Meier estimates will describe estimated event rates at 2 years. Time to muscle-invasive bladder cancer and time to death will be analyzed similarly.
- Time to death [From date of RNU to date of death, assessed up to 2 years]
Kaplan-Meier estimates will describe estimated event rates at 2 years. Time to muscle-invasive bladder cancer and time to death will be analyzed similarly.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Clinical diagnosis of localized (clinical American Joint Committee on Cancer [AJCC] stage Ta-T4N0M0) low- and high-grade UC of the renal pelvis and/or ureter
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Plan to undergo RNU
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Creatinine < 2.2 mg/dL (194 mmol/L)
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Hemoglobin > 9 g/dL
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White blood cell count >= 3000/uL
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Platelet count > 75,000/uL and < 500,000/uL
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Serum bilirubin levels below 2 times the institution's upper limits of normal
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Alkaline phosphatase levels below 2 times the institution's upper limits of normal
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Aspartate aminotransferase levels below 2 times the institution's upper limits of normal
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Alanine aminotransferase levels below 2 times the institution's upper limits of normal
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Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2
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Suitable candidate for surgery at the discretion of the investigator
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Patient must be capable of giving appropriate approved informed consent or have an appropriate representative available to do
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Patient with a prior malignancy allowed if adequately treated > 3 years ago with no current evidence of disease
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Women of childbearing potential (WOCBP) must have a negative pregnancy urine test within 28 days of registration, and be using an adequate method of contraception to avoid pregnancy prior to and for at least 6 months after gemcitabine instillation to minimize the risk of pregnancy
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Male patient who has a partner that is a WOCBP must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) and should avoid conceiving children prior to and for 6 months following gemcitabine instillation
Exclusion Criteria:
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Pure non-urothelial histology; urothelial carcinoma with differentiation allowed
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Evidence of nodal or distant metastases; enlarged retroperitoneal lymph nodes > 2 cm or histologically positive lymph nodes
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History of UC of the bladder within 12 months preceding RNU, or receipt of intravesical therapy within 6 months
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History of or current prostatic urethral, urethral, or contralateral upper tract UC
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Planned radical cystectomy at time of RNU
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Symptomatic urinary tract infection of bacterial cystitis (once satisfactorily treated, patients can enter the study)
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Patient with any current malignancy except for basal or squamous cell skin cancers, noninvasive cancer of the cervix, or any other cancer deemed to be of low-risk for progression or patient morbidity during the trial period (i.e. Gleason 6 prostate cancer, renal mass < 3 cm)
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Women who are pregnant or breastfeeding
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Prisoners or subjects who are involuntarily incarcerated
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Inability for adequate follow-up, including concerns for patient compliance or geographic proximity
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224-9980 |
| 2 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 3 | Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | United States | 27157 |
| 4 | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | United States | 15232 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Stephen A Boorjian, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19-009444
- NCI-2020-03336
- 19-009444
- P30CA015083