A Prospective Open Label Comparative Dose Ranging Study Evaluating the Effect of Pre-TURBT Intravesical Instillation of Mitomycin C (MMC) Mixed With TC-3 Gel in Patients With Non Muscle Invasive Bladder Cancer (NMIBC) (NMIBC TURBT HG)
This study is a prospective randomized open labeled dose ranging comparative study. Twenty four (24) patients with NMIBC who meet the inclusion/exclusion criteria will be recruited for the study following the initial diagnostic cystoscopy.
The investigators believe that this study is of importance on several aspects:
- It evaluates a new mode of bladder instillation that may bypass the drawbacks of the current instillation mode.
- If proved effective, this mode of treatment might save the need for TURBT performance and serve as a new mode of tumor ablation.
- Even if proved partially effective, this mode of treatment will diminish tumors size and/or number, thus enable a more limited TURBT procedure.
- This mode of treatment will enable immediate medical attendance to the patient's tumor recurrence without the waiting period (resulting from queues in the medical centers) for TURBT. This might improve the patient's prognostic outcome.
- If this experimental treatment will prove to have a better ablative effect in comparison to the standard of care known in the art, this could be translated to a better prophylactic effect of tumor recurrence.
- Finding the minimal, yet optimal, effective dose for tumor ablation and tumor recurrence prevention will enable us to reduce adverse effects of higher drug dosage.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective Open Label Comparative Dose Ranging Study Evaluating the Effect of Pre-TURBT Intravesical Instillation of Mitomycin C (MMC) Mixed With TC-3 Gel in Patients With Non Muscle Invasive Bladder Cancer (NMIBC)|
- Ablative effect of pre-TURBT intravesical instillations with 20,40,80 mg of MMC mixed with 60cc TC-3 Hydrogel on bladder lesion(s) of NMIBC patients [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Cystoscopic and pathological effect (evaluated during TUR-BT visit) of pre-TURBT intravesical instillations with 20,40,80 mg of MMC mixed with 60cc TC-3 Hydrogel on bladder lesion(s) of NMIBC patients.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability rate. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Demonstration of Pre-TURBT TC-3 gel-MMC instillation safety and adverse event rate.Adverse events will be defined as any adverse change in health or side effect that occurs in the clinical trial participant while the patient is receiving the treatment or until the completion of the post-treatment follow-up cystoscopy.
- Comparison of the cystoscopic and pathological effect between the 3 groups. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Comparison of the cystoscopic and pathological effect of pre-TURBT instillations between the 3 different dosages of MMC mixed with TC-3 Hydro-gel groups on bladder lesion(s).
- one year tumor recurrence rate [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Comparison of one year tumor recurrence rate between the 3 treatment groups
- PK level of MMC-C in blood [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]Demonstration that blood levels of MMC following Pre-TURBT TC-3 gel-MMC instillation are below the toxic level (400ng/ml) known in the art for IV MMC administration
|Study Start Date:||March 2013|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Group A: 20 mg MMC mixed with 60cc TC-3
Group A: 20 mg MMC mixed with 60cc TC-3 hydrogel. (n=8)
|Device: TC-3 hydrogel|
Experimental: • Group B: 40 mg MMC mixed with 60cc TC-3
• Group B: 40 mg MMC mixed with 60cc TC-3 hydrogel (n=8)
|Device: TC-3 hydrogel|
Experimental: • Group C: 80 mg MMC mixed with 60cc TC-3 hydrogel (n=8)
• Group C: 80 mg MMC mixed with 60cc TC-3 hydrogel (n=8)
|Device: TC-3 hydrogel|
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 such as Mitomycin C (MMC) or BCG. Unfortunately, this treatment approach is limited due to rapid dilution of the chemotherapeutic drug by the incoming urine and clearance by urination.
TheraCoat's core technology is based on a reverse thermal biodegradable gel (TC-3 Gel) (low viscosity at cold temperature (5°C) and gel appearance at body temperature)for drug retention in the urinary bladder.
Prior to instillation, the TC-3 Gel, in its liquid state, is mixed with MMC and instilled into the bladder by a standard catheter. Once inside the bladder, the gel solidifies and forms a drug reservoir. Upon contact with urine, the gel dissolves, release the drug slowly and is finally cleared out from the bladder.
Intravesical MMC instillation using TheraCoat's gel is expected to increase treatment efficiency due to prolongation of treatment duration and consequently improving bladder exposure to MMC.
Treatment Protocol - Immediately following baseline cystoscopy and tumor diagnosis and patient undergoes 6 weekly instillations followed by 2-4 weeks healing period.
1st Follow-Up Visit (Pre-Scheduled TURBT Visit): The patient will undergo a second cystoscopy to compare to baseline status. The patient will be followed-up for a period of 1 year as follows: 3,6,9,12 months.
|Contact: Michal Jeshurun-Gutshtat, MDfirstname.lastname@example.org|
|Contact: Nadav Malchiemail@example.com|
|Meir Medical Center||Recruiting|
|Kfar Saba, Israel|
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|Principal Investigator: Ilan Leibovich, MD|
|Western Galilee Hospital Nahariya||Recruiting|
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|University Hospital of Florence||Recruiting|
|Contact: Alberto Lapini, MD firstname.lastname@example.org|
|Principal Investigator: Alberto Lapini, MD|
|San Rafaelle Medical Center||Recruiting|
|Contact: Renzo Colombo, MD email@example.com|
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|Contact: Juan Palou Redorta, MD firstname.lastname@example.org|
|Principal Investigator: Juan Palou Redorta, MD|