Pre-TURBT TC-3 Gel Intravesical Instillation in NMIBC (OPTIMA)
In the proposed study the investigators aim to evaluate the effect of the standard of care dose (40mg) of MMC mixed with TC-3 gel (with sustained release mechanism on the drug) on low risk recurrent NMIBC lesions and to compare our findings to instillation with the standard mode of instillation- 40mg MMC in water in order to examine our hypothesis that MMC mixed with TC-3 gel will have at least non-inferior and even superior results over the standard instillation mode
The investigators believe that this study is of importance of 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 of TURBT performance and serve as a new mode of tumor ablation.
- Even if proved partially effective this mode of treatment will diminish tumors size 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, which might improve the patient's prognostic outcome.
- If this experimental treatment will prove to have a better ablative effect, this could be translated to a better prophylactic effect of tumor recurrence.
|Carcinoma of Urinary Bladder, Superficial||Device: 40 mg MMC gel Other: Standard of care MMC mixed with water Device: 80 mg MMC gel|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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 of the treatments on The bladder lesion(s) of NMIBC patients [ Time Frame: 2 years ]Cystoscopic and pathological effect (evaluated during TUR-BT visit) of pre-TURBT intravesical instillations with 40 mg of MMC mixed with 60cc TC-3 Hydrogel on bladder lesion(s) of NMIBC patients. At To, which is the time of identification of a recurrent tumor by cystoscopy, the number, size and location of the lesions will be documented and photographed. Each tumor size will be evaluated by photographing a ureter catheter adjacent to the tumor. Since the ureter catheter diameter is a pre-known variable, the tumor diameter can be calculated using specific software developed for study purposes. Photography of the tumor with a pre-known diameter ureter catheter will be performed during the same cystoscopy as described above and will be evaluated by a central clinic for uniformity of measurements, and the results of these measurements will serve for the post study evaluation of the change in tumor diameter
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability rate. [ Time Frame: 2 years ]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 2 groups. [ Time Frame: 2 years ]• Comparison of the cystoscopic and pathological effect of pre-TURBT instillations with MMC mixed with TC-3 Hydrogel on bladder lesion(s) to that of pre-TURBT MMC in water instillation groups
- • Comparison of one year tumor recurrence rate between both treatment groups [ Time Frame: 2 years ]
- • 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 [ Time Frame: 1 year ]
|Study Start Date:||June 2013|
|Study Completion Date:||June 2017|
|Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: 40 mg MMC gel
Device: TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 60 cc of TC-3 gel mixed with 40 mg MMC will be instilled using catheter.
Other Name: MMC Gel
Device: 40 mg MMC gel
A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder.
Other Name: MMC-Gel
Active Comparator: Standard of care MMC mixed with water
40 mg MMC mixed with 40cc water. Six weekly intravesical instillations of 40 mg of MMC mixed with 40 cc of water will be instilled using catheter
Other: Standard of care MMC mixed with water
Standard of care 40mg MMC mixed with water
Experimental: 80 mg MMC gel
Device: TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 60 cc of TC-3 gel mixed with 80 mg MMC will be instilled using catheter.
Other Name: MMC Gel
Device: 80 mg MMC gel
A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder
Other Name: MMC-Gel
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) or BCG. 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 biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug 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 instillation using TheraCoat 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 the Baseline status and after that a follow-up period: 3,6,9,12 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01803295
|Carmel Medical Center of Haifa, Department of Urology|
|Rambam Health Care Campus|
|Wolfson Medical Center of Holon, Department of Urology|
|Meir medical center|
|Kfar Saba, Israel|
|Galil Maaravi Medical Center of Nahariya, Department of Urology|
|Rabin Medical Center of Petah Tikva, Department of Urology|
|Petach Tikvah, Israel|
|Ziv Medical Center|
|Vita Salute University, San Raffaele Hospital of Milan, Department of Urology|
|S. Andrea Hospital of Rome, Department of Urology|
|Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona|
|Hospital Universitario Infanta Sofìa of Madrid, Department of Urology|
|Hôpital HUG of Geneva, Department of Urology|
|Principal Investigator:||Fred Witjes, Prof||Radboud University Nijmegen Medical Centre, Department of Urology Geert Grooteplein South 10 (659), Nijmegen|
|Principal Investigator:||Stenzl, Prof.||Tübingen Universitätsklinik für Urologie|