Intravesical Gemcitabine in Patients With NMIBC

Study Overview
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Brief Summary
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Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumor recurrence after bladder tumor resection. For high-risk non-muscle invasive bladder cancer, immunotherapy in the form of intravesical Bacillus Calmette-Guérin (BCG) can be effective as first-line, nevertheless, the response rate to BCG is suboptimal with many patients failing treatment. Following BCG-failure, however, very few effective therapeutic options exist besides life-changing cystectomy. In addition, nationwide shortages of BCG have pushed the use of alternative intravesical therapies for non-muscle invasive bladder cancer. At Banner University Medical-Tucson, the use of intravesical Gemcitabine is considered as standard treatment for patients with bladder cancer who are unable to get BCG or have failed prior BCG treatment. The role of Gemcitabine as treatment for NBMIC is poorly understood. The purpose of this study is to gain a better understanding of the use of Gemcitabine intravesical chemotherapy for non-muscle invasive bladder cancer in a prospective cohort of patients.

Official Title
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Phase II Trial of Intravesical Gemcitabine in Patients With Nonmuscle Invasive Bladder Cancer With or Without Prior Bacillus Calmette-Guérin Therapy

Conditions
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Urinary Bladder Cancer

Intervention / Treatment
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* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients able to consent in English or Spanish; provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female ages ≥18 years. Patients with intermediate or high-risk non-muscle-invasive UC of the bladder and no previous BCG treatment. Histologically confirmed intermediate or high-risk non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on Transurethral Resection of Bladder Tumor (TURBT) must be obtained within 180 days of registration. OR Patients with a high-grade recurrence after 24 months since last dose of BCG. 6. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2. 7. Post-transurethral bladder tumor resection. 8. Evidence of post-menopausal status or negative urinary pregnancy test of female pre-menopausal patients is required. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Exclusion Criteria: Known hypersensitivity reaction to gemcitabine. Clinical T2 or higher stage UC of the bladder. Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure CIS of the bladder. Active malignancies other than the disease being treated under study. Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial carcinoma of any stage. Pregnant or breast-feeding women. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine induction<br>Patients will receive Gemcitabine once weekly for 6 weeks. | Drug: Gemcitabine<br>* Gemcitabine will be administered intravesically at a dose of 2000 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CR) for treatment with intravesical gemcitabine for patients with intermediate and high-risk NMIBC | The primary outcome measure will be CR rate, defined as the percentage of patients with CR at the 3-month visit. An event will be defined as the earliest date of recurrence as determined using the date of cystoscopy, biopsy, or cytology, whichever occurs first. | Complete response rate will be measured at the 3-month visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of response in patients who achieve CR | To assess durable CR in patients who achieved CR at the 3-month visit, defined as the percentage of patients with no detectable disease 6, 9, and 12 months after treatment initiation. Duration of CR will be defined as the time from the date of evidence of CR at the 3-month visit to the earliest date of recurrence. | Duration of CR will be measured as change from the 3-month visit up to 12 months after treatment initiation | 
| Tolerability and safety of the treatment | To assess adverse events using the Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be monitored during the course of treatment, and a toxicity assessment will be done after completion of treatment that will descriptively summarize any treatment-related adverse events that occur on or after the date of the first instillation of gemcitabine. | Toxicity assessment will be evaluated at the 3-month visit | 
| Proportion of patients who accept maintenance therapy | To assess the number of patients who are agreeable to monthly maintenance therapy for 10 months as per patient and physician discretion. | The assessment will be done at the 3-month visit | 
| Rate and reasons for cystectomy (if any) | To assess rate of salvage cystectomy and reasons for cystectomy at the time of tumor recurrence (if any) after treatment with gemcitabine. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacillus Calmette-Guérin (BCG), Nonmuscle invasive bladder cancer (NMIBC), Intravesical immunotherapy, Post-transurethral resection