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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma of Urinary Bladder, Invasive
• Intervention / Treatment: Device: TC-3 gel; Device: TC-3 gel mixed with Mitomycin C (MMC)

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel
    • Barzilai Hospital
  • Holon, Israel
    • Wolfson
  • Petah-Tikva, Israel
    • Beilinson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: UroGen Pharma Ltd.
• Investigators: Study Director: Michal Jeshurun, MD, UroGen Pharma Ltd.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: July 17, 2012
• First Submitted That Met QC Criteria: July 23, 2012
• First Posted (Estimate): July 24, 2012

Study Record Updates

• Last Update Posted (Estimate): May 7, 2013
• Last Update Submitted That Met QC Criteria: May 6, 2013
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Non Muscle Invasive Bladder Cancer; Mitomycin C; radical cystectomy; Hydrogel; Carcinoma of urinary bladder, invasive; Intravesical instillation; Reverse thermal gelation; Drug retention
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: TAS-4M-PR-H-127-1; HTA 5972 (Other Identifier: Israeli Ministry of Health)