Back to resultsGemcitabine for the Prevention of Intravesical Recurrence of Urothelial Cancer in Patients With Upper Urinary Tract Urothelial Cancer Undergoing Radical Nephroureterectomy, GEMINI Study
Primary Purpose
Stage 0a Renal Pelvis and Ureter Cancer AJCC v8, Stage 0a Renal Pelvis Cancer AJCC v8, Stage 0a Ureter Cancer AJCC v8
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine Hydrochloride
Sponsored by
About this trial
This is an interventional prevention trial for Stage 0a Renal Pelvis and Ureter Cancer AJCC v8
Eligibility Criteria
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:
- 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
Sites / Locations
- Mayo Clinic in Florida
- Mayo Clinic in Rochester
- Wake Forest Baptist Medical Center
- University of Pittsburgh Cancer Institute (UPCI)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Prevention (gemcitabine hydrochloride)
Arm Description
Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU.
Outcomes
Primary Outcome Measures
Urothelial Carcinoma Relapse-free Survival
Number of participants without recurrence of Urothelial Carcinoma. Relapse-free survival will be assessed by cystoscopy and urine cytology.
Secondary Outcome Measures
Time to Recurrence
Number of days from Radical Nephroureterectomy to date of histologic proof of recurrence/relapse of Urothelial Carcinoma
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04398368
Brief Title
Gemcitabine for the Prevention of Intravesical Recurrence of Urothelial Cancer in Patients With Upper Urinary Tract Urothelial Cancer Undergoing Radical Nephroureterectomy, GEMINI Study
Official Title
GEMINI: An Open-Label, Single-Arm, Phase II Study of Intraoperative Gemcitabine Intravesical Instillation in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Focus research efforts on other projects.
Study Start Date
June 5, 2020 (Actual)
Primary Completion Date
February 2, 2023 (Actual)
Study Completion Date
February 2, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prevention (gemcitabine hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011
Intervention Description
Given intravesically
Primary Outcome Measure Information:
Title
Urothelial Carcinoma Relapse-free Survival
Description
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 Outcome Measure Information:
Title
Time to Recurrence
Description
Number of days from Radical Nephroureterectomy to date of histologic proof of recurrence/relapse of Urothelial Carcinoma
Time Frame
Up to 1 year
Title
Incidence of Adverse Events
Description
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 Pre-specified Outcome Measures:
Title
Incidence of Muscle-invasive Bladder Cancer
Description
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
Title
Time to Development of Muscle-invasive Bladder Cancer
Description
Defined as the time (days) from date of Radical Nephroureterectomy to date of histologic proof of Urothelial Carcinoma
Time Frame
Up to 2 years
Title
Time to Death
Description
Defined as the time (days) from date of Radical Nephroureterectomy to date of death
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen A Boorjian
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Gemcitabine for the Prevention of Intravesical Recurrence of Urothelial Cancer in Patients With Upper Urinary Tract Urothelial Cancer Undergoing Radical Nephroureterectomy, GEMINI Study
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