A Study of TAR-200 in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate both the safety and tolerability of up to 4 dosing cycles of TAR-200 for 21 days per dosing cycle in the induction period.

Official Title
-----------------
A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy

Conditions
-----------------
Urinary Bladder Neoplasms

Intervention / Treatment
-----------------
* Drug: TAR-200


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the bladder Participant must have been as fully resected as possible per the physician's judgment Participants must be deemed unfit for RC due to comorbid conditions with a risk of mortality Participants must refuse or be deemed ineligible for cisplatin-based chemotherapy Participant must refuse or not be eligible for radiotherapy Exclusion Criteria: Other active malignancies Presence of any bladder or urethral anatomic feature that in the opinion of the Investigator may prevent the safe placement, indwelling use, or removal of TAR-200 Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy tube is allowed) Evidence of bladder perforation during diagnostic cystoscopy Concurrent clinically significant infections as determined by the treating Investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants Ineligible for Radical Cystectomy<br>Participants will receive the TAR-200 transuretherally on Day 0 in to the bladder through an Inserter and gradually releases gemcitabine during the 21-day indwelling period before being removed on Day 21 via flexible or rigid cystoscopy. Participants will undergo an 84-day induction period comprised of four consecutive 21-day dosing cycles. Participants may undergo 21 day cycle every 3 months for a maximum of 3 cycles as maintenance (Up to 14 months). Each TAR-200 system will be removed at 21 days after insertion. | Drug: TAR-200<br>* TAR-200 will be placed for 21-day dosing cycles, with up to 7 doses per participant.<br>* Other names: Gemcitabine-Releasing Intravesical System (GemRIS);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | An Adverse Event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the intervention under study. | Up to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Complete Response (cCR) | Percentage of Participants with Clinical Complete Response (cCR) will be reported as assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated). | Up to Day 360 | 
| Percentage of Participants with Clinical Partial Response (cPR) | Percentage of participants with clinical partial response (cPR) will be reported as assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated). | Up to Day 360 | 
| Percentage of Participants with Stable Disease (SD) | Percentage of participants with stable disease (SD) will be reported as assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated). | Up to Day 360 | 
| Percentage of Participants with Disease Progression | Percentage of participants with disease progression as assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated) | Up to Day 360 | 
| Symptom Control | Symptom Control is defined as changes in bladder-related symptoms per the protocol-specified bladder symptom (Urinary frequency, Nocturia, Hematuria and Dysuria/pain) and toxicity grading system (Grade 0-3). | Up to Day 360 | 
| Time to Intervention for Symptom Control | Time to intervention for symptom control, defined as the time from the date of the first TAR-200 insertion to the date of intervention for symptom palliation. | Up to Day 360 | 
| Time to Progression | Time to progression, defined as the time from the date of the first TAR-200 insertion to the date of first occurrence of progression. | Up to Day 360 | 
| Percentage of Participants Undergoing Post-treatment Interventions by 3, 6, 9, and 12 Months | Percentage of participants undergoing post-treatment interventions for the management of local symptoms by 3, 6, 9, and 12 months. | Up to 3, 6, 9, and 12 Months | 
| Percentage of Participants Surviving at 12, 24, and 36 Months | Percentage of participants surviving at 12, 24, and 36 months compared to all participants. | At 12, 24, and 36 months |