Safety and Tolerability Study Which Evaluate Intravesical Instillation With Mitomycin C Mixed With TC-3 Drug Retaining Hydrogel Device In Patients With Muscle Invasive Bladder Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety of intravesical instillation of TC-3 Hydrogel disposable device for retention of mitomycin C chemotherapeutic drug in the urinary bladder.

Detailed Description
-----------------
Non-muscle-Invasive Bladder cancer is mainly treated by tumor resection (Trans Urethral Resection - TUR), followed by series of intravesical instillations of prophylactic chemotherapeutic drugs as Mitomycin C (MMC).This treatment approach is limited due to rapid dilution the chemotheraputic drug by the incoming urine and clearance by urination. TheraCoat core technology is based on a reverse thermal (low viscosity at 5°C) degradable gel (TC-3)for MMC retention in the urinary bladder. Prior to instillation, the TC-3 hydrogel,in a liquid state, is mixed with MMC.TC-3 mixed with MMC is instilled to the bladder by a catheter.Following gel insertion to the bladder, the gel solidifies and forms a drug reservoir inside the bladder. Upon contact with urine the gel dissolves and is cleared out from the bladder. Intravesical MMC using TheraCoat gel is expected to increase treatment efficiency due to prolongation of treatment duration and consequently improving bladder exposure to MMC.

Official Title
-----------------
An Open Label Study Evaluating Short Term Safety and Tolerability of Patients With MUSCLE INVASIVE BLADDER CANCER- for Intravesical Instillation Mitomycin c Mixed With Disposable Device Which Prevents Drug Drainage Out of the Patient's Bladder

Conditions
-----------------
Carcinoma of Urinary Bladder, Invasive

Intervention / Treatment
-----------------
* Device: TC-3 gel
* Device: TC-3 gel mixed with Mitomycin C (MMC)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form. Patients with bladder cancer designated to undergo Radical Cystectomy Exclusion Criteria: Sensitivity to MMC Acute urinary Tract Infection (UTI) Upper urinary tract obstruction. Patient received neoadjuvant treatment previous to Radical Cystectomy Pregnant women as diagnosed by Beta - HCG, or women that are suspected to be pregnant Breastfeeding women

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

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

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

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

Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TC-3 gel<br>TC-3 gel group undergo intravesical instillation of the investigatory device | Device: TC-3 gel<br>* One intravesical instillation of 40 cc of TC-3 hydrogel is instilled using catheter.<br>|
| Experimental: MMC- gel<br>MMC gel group undergo intravesical instillation of the reverse thermal gelation device mixed with MMC | Device: TC-3 gel mixed with Mitomycin C (MMC)<br>* One intravesical instillation of 40 cc of TC-3 gel mixed with 40 mg MMC will be instilled using catheter<br>* Other names: MMC Gel;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of systemic and urine pharmacokinetics of MMC following intravesical instillation of TC-3 mixed with MMC for safety evaluation. | Study participants undergoing bladder instillation with MMC mixed with TC-3 6 hours prior to radical cystectomy. During these six hours the MMC levels in urine and blood will be measured every hour and the Peak Plasma Concentration (Cmax)and Area under the plasma concentration versus time curve (AUC) will be calculated and compared to the standard toxicity level in patients treated with MMC in saline (standard of cure). In addition, patient tolerability to treatment will be evaluated. | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the levels of MMC in patients urinary bladder following intravesical instillation of TC-3 mixed with MMC. | Study participants undergoing bladder instillation with MMC mixed with TC-3 6 hours prior to radical cystectomy. Local (bladder) tissue levels of MMC will be evaluated and compared to MMC levels detected following treatment with MMC in saline (standard of cure). | 6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non Muscle Invasive Bladder Cancer, Carcinoma of urinary bladder, invasive, Intravesical instillation, Mitomycin C, Hydrogel, Reverse thermal gelation, Drug retention, radical cystectomy