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

GEMINI: An Open-Label, Single-Arm, Phase II Study of Intraoperative Gemcitabine Intravesical Instillation in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Stage III Renal Pelvis Cancer AJCC v8; Stage III Ureter Cancer AJCC v8; Stage IV Renal Pelvis Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage III Renal Pelvis and Ureter Cancer AJCC v8; Stage IV Renal Pelvis and Ureter Cancer AJCC v8; 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
• Intervention / Treatment: Drug: Gemcitabine Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Gemzar; dFdCyd; Difluorodeoxycytidine Hydrochloride; FF 10832; FF-10832; FF10832; Gemcitabine HCI; LY-188011; LY188011

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recurrence	Number of days from Radical Nephroureterectomy to date of histologic proof of recurrence/relapse of Urothelial Carcinoma	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.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Up to 2 years
Time to Death	Defined as the time (days) from date of Radical Nephroureterectomy to date of death	Up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephen A Boorjian, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2020
• Primary Completion (Actual): February 2, 2023
• Study Completion (Actual): February 2, 2023

Study Registration Dates

• First Submitted: May 16, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Ureteral Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Pelvic Neoplasms; Ureteral Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: 19-009444 (Other Identifier: Mayo Clinic in Rochester); NCI-2020-03336 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No