TerminatedNCT04398368Updated Aug 8, 2023Results posted

Gemcitabine for the Prevention of Intravesical Recurrence of Urothelial Cancer in Patients With Upper Urinary Tract Urothelial Cancer Undergoing Radical Nephroureterectomy, GEMINI Study

A Phase 2 interventional study of Gemcitabine Hydrochloride in Stage 0a Renal Pelvis and Ureter Cancer AJCC v8, Stage 0a Renal Pelvis Cancer AJCC v8 and Stage 0a Ureter Cancer AJCC v8, sponsored by Mayo Clinic. Terminated at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-08.

Sponsored by Mayo Clinic · Phase 2, Interventional, and Prevention

Why this study was terminated

Focus research efforts on other projects.

Phase: Phase 2
Study type: Interventional
Enrollment: 25
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

PRIMARY OBJECTIVE:

I. 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:

I. To assess time to recurrence for entire duration of follow-up. II. To assess the qualitative and quantitative toxicities.

EXPLORATORY OBJECTIVES:

I. To stratify intravesical UC recurrence free survival by tumor grade, neoadjuvant chemotherapy, tumor stage, ureteral tumor location, and history of bladder cancer.

II. 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.

Conditions studied

Stage 0a Renal Pelvis and Ureter Cancer AJCC v8
Stage 0a Renal Pelvis Cancer AJCC v8
Stage 0a Ureter Cancer AJCC v8
Stage 0is Renal Pelvis and Ureter Cancer AJCC v8
Stage 0is Renal Pelvis Cancer AJCC v8
Stage 0is Ureter Cancer AJCC v8
Stage I Renal Pelvis and Ureter Cancer AJCC v8
Stage I Renal Pelvis Cancer AJCC v8
Stage I Ureter Cancer AJCC v8
Stage II Renal Pelvis and Ureter Cancer AJCC v8
Stage II Renal Pelvis Cancer AJCC v8
Stage II Ureter Cancer AJCC v8
Stage III Renal Pelvis and Ureter Cancer AJCC v8
Stage III Renal Pelvis Cancer AJCC v8
Stage III Ureter Cancer AJCC v8
Stage IV Renal Pelvis and Ureter Cancer AJCC v8
Stage IV Renal Pelvis Cancer AJCC v8
Stage IV Ureter Cancer AJCC v8

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In context

Ureteral Neoplasms

119 studies on the registry are indexed under Ureteral Neoplasms; 19 are open to participants now.

This study's enrollment of 25 is below the median of 42 across 96 interventional studies indexed under Ureteral Neoplasms.

Browse Ureteral Neoplasms studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
Plan to undergo RNU
Creatinine \< 2.2 mg/dL (194 mmol/L)
Hemoglobin > 9 g/dL
White blood cell count >= 3000/uL
Platelet count > 75,000/uL and \< 500,000/uL
Serum bilirubin levels below 2 times the institution's upper limits of normal
Alkaline phosphatase levels below 2 times the institution's upper limits of normal
Aspartate aminotransferase levels below 2 times the institution's upper limits of normal
Alanine aminotransferase levels below 2 times the institution's upper limits of normal
Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2
Suitable candidate for surgery at the discretion of the investigator
Patient must be capable of giving appropriate approved informed consent or have an appropriate representative available to do
Patient with a prior malignancy allowed if adequately treated > 3 years ago with no current evidence of disease
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
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

Exclusion Criteria:

Pure non-urothelial histology; urothelial carcinoma with differentiation allowed
Evidence of nodal or distant metastases; enlarged retroperitoneal lymph nodes > 2 cm or histologically positive lymph nodes
History of UC of the bladder within 12 months preceding RNU, or receipt of intravesical therapy within 6 months
History of or current prostatic urethral, urethral, or contralateral upper tract UC
Planned radical cystectomy at time of RNU
Symptomatic urinary tract infection of bacterial cystitis (once satisfactorily treated, patients can enter the study)
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)
Women who are pregnant or breastfeeding
Prisoners or subjects who are involuntarily incarcerated
Inability for adequate follow-up, including concerns for patient compliance or geographic proximity

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 25 participants (actual)

Study arms

Experimental
Prevention (gemcitabine hydrochloride)
Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU.
Drug: Gemcitabine Hydrochloride

Interventions

DrugGemcitabine Hydrochloride
Given intravesically
Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

What researchers measure

Primary outcomes

Urothelial Carcinoma Relapse-free Survival
Number of participants without recurrence of Urothelial Carcinoma. Relapse-free survival will be assessed by cystoscopy and urine cytology.
Time frame: Up to 1 year

Secondary outcomes

Time to Recurrence
Number of days from Radical Nephroureterectomy to date of histologic proof of recurrence/relapse of Urothelial Carcinoma
Time frame: Up to 1 year
Incidence of Adverse Events
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.
Time frame: Up to 2 years

Other outcomes

Incidence of Muscle-invasive Bladder Cancer
Number of subject to experience muscle-invasive bladder cancer. Assessed by Urothelial Carcinoma on final pathology of Transurethral Resection of Bladder Tumor specimen or Urothelial Carcinoma on final pathology of radical cystectomy specimen.
Time frame: Up to 2 years
Time to Development of Muscle-invasive Bladder Cancer
Defined as the time (days) from date of Radical Nephroureterectomy to date of histologic proof of Urothelial Carcinoma
Time frame: Up to 2 years
Time to Death
Defined as the time (days) from date of Radical Nephroureterectomy to date of death
Time frame: Up to 2 years

Results

Posted Aug 8, 2023

Limitations and caveats

Study target enrollment was anticipated for 90 participants but only 23 participants completed treatment before study was terminated. The study was terminated due to insufficient resources and funding to support continuation of the trial. PI decision to terminate.

Participant flow

Participant flow — Overall Study
Milestone	Prevention (Gemcitabine Hydrochloride)
Started	25
Completed	23
Not completed	2
Withdrew: Withdrawal by subject	2

Outcome measures

PrimaryUrothelial Carcinoma Relapse-free Survival

Number of participants without recurrence of Urothelial Carcinoma. Relapse-free survival will be assessed by cystoscopy and urine cytology.

Time frame:: Up to 1 year
Reported as:: Count of participants · Participants

Urothelial Carcinoma Relapse-free Survival
Participants	Prevention (Gemcitabine Hydrochloride)
Urothelial Carcinoma Relapse-free Survival	14

SecondaryTime to Recurrence

Number of days from Radical Nephroureterectomy to date of histologic proof of recurrence/relapse of Urothelial Carcinoma

Time frame:: Up to 1 year
Reported as:: Mean · Days

Time to Recurrence
Days	Prevention (Gemcitabine Hydrochloride)
Time to Recurrence	178.75 ± 136.39

SecondaryIncidence of Adverse Events

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.

Time frame:: Up to 2 years
Reported as:: Number · Adverse Events

Incidence of Adverse Events
Adverse Events	Prevention (Gemcitabine Hydrochloride)
Incidence of Adverse Events	213

Other pre-specifiedIncidence of Muscle-invasive Bladder Cancer

Number of subject to experience muscle-invasive bladder cancer. Assessed by Urothelial Carcinoma on final pathology of Transurethral Resection of Bladder Tumor specimen or Urothelial Carcinoma on final pathology of radical cystectomy specimen.

Time frame:: Up to 2 years
Reported as:: Count of participants · Participants

Incidence of Muscle-invasive Bladder Cancer
Participants	Prevention (Gemcitabine Hydrochloride)
Incidence of Muscle-invasive Bladder Cancer	4

Other pre-specifiedTime to Development of Muscle-invasive Bladder Cancer

Defined as the time (days) from date of Radical Nephroureterectomy to date of histologic proof of Urothelial Carcinoma

Time frame:: Up to 2 years
Reported as:: Mean · Days

Time to Development of Muscle-invasive Bladder Cancer
Days	Prevention (Gemcitabine Hydrochloride)
Time to Development of Muscle-invasive Bladder Cancer	178.75 ± 136.39

Other pre-specifiedTime to Death

Defined as the time (days) from date of Radical Nephroureterectomy to date of death

Time frame:: Up to 2 years
Reported as:: Mean · Days

Time to Death
Days	Prevention (Gemcitabine Hydrochloride)
Time to Death	543 ± 379.97

Adverse events

Collected over Adverse events were collected from baseline to end of study participation for a total of approximately 24 months on all participants.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Prevention (Gemcitabine Hydrochloride)	3/25 (12%)	4/25 (16%)	19/25 (76%)

Most frequent serious events

Most frequent serious events
Event	Prevention (Gemcitabine Hydrochloride)
Cancer recurrenceRenal and urinary disorders	4/25
atrioventricular block (complete)Cardiac disorders	1/25
Respiratory failureRespiratory, thoracic and mediastinal disorders	1/25
Nectrotic segment of small intestineGastrointestinal disorders	1/25

Most frequent other events

Showing 10 of 106

Most frequent other events
Event	Prevention (Gemcitabine Hydrochloride)
Weakness/FatigueNervous system disorders	7/25
NauseaGastrointestinal disorders	6/25
Urinary Tract InfectionInfections and infestations	5/25
HypertensionGeneral disorders	5/25
Elevated creatinineBlood and lymphatic system disorders	5/25
NocturiaRenal and urinary disorders	4/25
Acute Kidney InjuryRenal and urinary disorders	4/25
Chronic Kidney DiseaseRenal and urinary disorders	4/25
Low platelet countBlood and lymphatic system disorders	4/25
abdominal painGastrointestinal disorders	3/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Prevention (Gemcitabine Hydrochloride)
Mean	72.38 ± 8.84

Sex: Female, Male
Sex: Female, Male(Participants)	Prevention (Gemcitabine Hydrochloride)
Female	10
Male	15

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Prevention (Gemcitabine Hydrochloride)

Region of Enrollment
Region of Enrollment(participants)	Prevention (Gemcitabine Hydrochloride)
United States	25

Study locations

4 sites

Mayo Clinic in Florida
Jacksonville, Florida 32224-9980, United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina 27157, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232, United States

References and documents

Study documents

Protocol and statistical analysis plan · Sep 3, 2021

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 8, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04398368
Lead sponsor: Mayo Clinic
Responsible party: Stephen A. Boorjian, M.D. (Principal Investigator, Mayo Clinic) — Principal investigator
First posted: May 21, 2020
Start date: Jun 5, 2020
Primary completion: Feb 2, 2023
Completion: Feb 2, 2023
Results posted: Aug 8, 2023
Last update: Aug 8, 2023

Study contacts

Stephen A Boorjian

principal investigator · Mayo Clinic

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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