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 currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by TheraCoat Ltd.
Sponsor:
Information provided by (Responsible Party):
TheraCoat Ltd.
ClinicalTrials.gov Identifier:
NCT01803295
First received: February 21, 2013
Last updated: November 24, 2013
Last verified: February 2013
  Purpose

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:

  1. It evaluates a new mode of bladder instillation that may bypass the drawbacks of the current instillation mode.
  2. If proved effective this mode of treatment might save the need of TURBT performance and serve as a new mode of tumor ablation.
  3. Even if proved partially effective this mode of treatment will diminish tumors size or number thus enable a more limited TURBT procedure.
  4. 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.
  5. If this experimental treatment will prove to have a better ablative effect, this could be translated to a better prophylactic effect of tumor recurrence.

Condition Intervention
Non Muscle Invasive Bladder Cancer
Device: TC-3 Gel
Other: Standard of care MMC mixed with water

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by TheraCoat Ltd.:

Primary Outcome Measures:
  • ablative effect of pre-TURBT intravesical instillations of the treatments on The 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 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 ] [ 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.


Other Outcome Measures:
  • Comparison of the cystoscopic and pathological effect between the 2 groups. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
  • • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MMC gel group Patients

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: TC-3 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: MMC standard of care group
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

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) 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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Single or multiple tumors (n≤7)
  • Recurrent tumor.
  • No prior history of HG and/or T1 and/or Tis
  • At least one Tumor ≥ 1mm.
  • Largest tumor diameter ≤ 30mm
  • Cystoscopic appearance of papillary Low grade tumor
  • The patient had upper urinary tract evaluation in the previous year excluding urothelial carcinoma, hydronephrosis,Renal Cell Carcinoma or other renal cancers.
  • Good performance status (Karnofsky performance status 70% or greater).

Exclusion Criteria:

  • Sensitivity to MMC
  • Acute urinary Tract Infection(UTI)
  • Upper urinary tract obstruction.
  • Treatment with intravesical chemotherapy within the 3 last months
  • Cystoscopic Appearance suspicious for HG and/or solid and/or Tis
  • The patient did not have at least 3 months cystoscopically confirmed tumor-free interval between the last tumor recurrence and screening.
  • Pregnant women as diagnosed by Beta - HCG, or women that are suspected to be --pregnant
  • Brest feeding women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803295

Contacts
Contact: Michal Jeshurun-Gutshtat, MD 972-52-8770775 michal.jeshurun@theracoat.com
Contact: Nadav Malchi 972-52-6543306 nadav.malchi@theracoat.com

Locations
Israel
Meir medical center Recruiting
Kfar Saba, Israel
Contact: Ilan Leibovitch, Prof       leibovitchi@clalit.org.il   
Principal Investigator: Ilan Labovich, Prof         
Italy
University hospital of Florence Recruiting
Florence, Italy
Contact: Alberto Lapini, MD    +393386622330    lapinial@gmail.com   
Principal Investigator: Alberto Lapini, MD         
Spain
Fundacio Puigvert Recruiting
Barcelona, Spain
Contact: Juan Palou Redorta, MD/PhD         
Principal Investigator: Prof Palou, MD/PhD         
Sponsors and Collaborators
TheraCoat Ltd.
Investigators
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
  More Information

No publications provided

Responsible Party: TheraCoat Ltd.
ClinicalTrials.gov Identifier: NCT01803295     History of Changes
Other Study ID Numbers: TAS-4M-CS-0002-0
Study First Received: February 21, 2013
Last Updated: November 24, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by TheraCoat Ltd.:
Non Muscle Invasive Bladder Cancer
Intravesical instillation
Mitomycin C
Hydrogel Reverse thermal gelation
Drug retention
Intravesical Instillation
Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Nucleic Acid Synthesis Inhibitors
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014