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

NCT04398368 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-009444NCI-2020-03336
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Time to Recurrence

  Up to 1 year

• Incidence of Adverse Events

  Up to 2 years

Other Outcomes (3)

• Incidence of Muscle-invasive Bladder Cancer

  Up to 2 years

• Time to Development of Muscle-invasive Bladder Cancer

  Up to 2 years

• Time to Death

  Up to 2 years

Study Arms (1)

Prevention (gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride intravesically for at least 1 hour at the time of RNU.

Drug: Gemcitabine Hydrochloride

Interventions

Gemcitabine Hydrochloride DRUG

Given intravesically

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

Prevention (gemcitabine hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (4)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Ureteral Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ureteral Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

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.

Results Point of Contact

• Title: Stephen A. Boorjian, M.D.
• Organization: Mayo Clinic

Boorjian.Stephen@mayo.edu

507 422-5516

Study Officials

• Stephen A Boorjian

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2020
• First Posted: May 21, 2020
• Study Start: June 5, 2020
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: August 8, 2023
• Results First Posted: August 8, 2023

Record last verified: 2023-07

Locations

US (4)