Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02471547
Recruitment Status : Unknown
Verified April 2016 by Prof. Jacob Ramon, Sheba Medical Center.
Recruitment status was:  Recruiting
First Posted : June 15, 2015
Last Update Posted : April 28, 2016
Sponsor:
Information provided by (Responsible Party):
Prof. Jacob Ramon, Sheba Medical Center

Tracking Information
First Submitted Date  ICMJE May 27, 2015
First Posted Date  ICMJE June 15, 2015
Last Update Posted Date April 28, 2016
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
Recurrence rate of Urothelial carcinoma (UC) of bladder [ Time Frame: Two years ]
Reduced recurrence rate of Urothelial carcinoma (UC) of bladder among patients receiving intravesical heated installations
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT
Official Title  ICMJE Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT- Prospective Controlled Study
Brief Summary

Transurethral Resection of Bladder Tumor (TURBT) is the initial treatment procedure for urinary bladder cancer. Recurrence rate during the first year ranges between 15-38% in case of low-intermediate disease. Current literature advocate using intravesical instillations of Mitomycin-C (MMC) immediately post TURBT in order to reduce the rate of recurrence.

During the last decade, heated intravesical instillations have emerged as additional players, in the treatment of recurrent disease. By most cases, the heated intravesical instillations are given either by microwave hyperthermia (synergo®) or by conductive heat bladder wall thermo-chemotherapy (BWT).

Previous reports suggest up to 59% reduction rate in recurrence following thermo-chemotherapy upon recurrent disease. These outstanding reduction results haven't convinced significant amount of urologists worldwide to use the intravesical instillation close after endoscopic resection as TURBT, probably due to the fear of MMC adverse effects in an operated area or the fear of complications due to perforated bladder. Preliminary results have suggested favourable outcome when MMC is used prior to TURBT [see publication]. To the investigators' knowledge no previous study has prospectively examined the effect of preliminary heated intravesical installation with BWT.

Detailed Description

Scientific hypothesis: Patients treated with preliminary intravesical installation in a timely fashion before TURBT are expected to show lower recurrence rate and better outcome then control patients.

Participants: Three hundred patients designed to undergo TURBT in the urology department at "Sheba" Medical Center at "Tel Hashomer", Israel.

Exiting the research:

  1. Patient is not completing the procedure due to allergic reaction or serious adverse effect during the heated intravesical instillation .
  2. Patient having according to pathology report muscle invasive bladder cancer (MIBC) and expects to undergo cystectomy.

Protocol steps Eligible patients give their consent to participate in the study. A preliminary grouping (for low, intermediate and high risk groups) will be initiated according to cystoscopy examination results. (this step is for administrative purpose in order to achieve equal amount of participants between groups during follow-up phase) Then participants will randomly assign, according to randomized computer software to two major arms, those who receive the heated thermo-chemo therapy and those who will not. The intravesical instillation will take place up to 6 hours prior TURBT in the following matter: The "Elmedical" system will introduce intravesically a 40mg of heated Mitomycin-C (MMC), diluted in 50cc of saline at a uniform temperature (44-44.50C). The length of the procedure - 50 minutes.

Once pathological reports will arrive, the participant will assign to his/her actual risk group stratification. Participants with recurrent disease will be assigned into separated intermediate or high risk groups accordingly.

consequently five stratification groups are created in each major research arm (with or without prior heated intravesical instillation) Follow-up of each participant, at any group takes two years. During the follow-up period a urine cytology and routine cystoscopy will be carried out every 3 month. Patients with intermediate to high risk disease will receive six courses of intravesical bacillus Calmette-Guerin (BCG) installation according to international guidelines. Participants who for any reason won't be able to complete the BCG intravesical instillations will be offered a MMC instillation instead. Participant that pathological report is indicating a muscle invasive disease will be offered a cystectomy and exit the study (unless the participant avoids cystectomy by his/her own decision).

The investigators are obligate ourselves for surveillance according to international guidelines (as intravesical instillations of BCG or performing repeat TURBT / Biopsy by need).

Potential bias: Different surgical skills between urologists, Quality of pre-TURBT installation of thermo-chemotherapy.

Duration: Four years with two years follow up per participant.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Transitional Cell Carcinoma
Intervention  ICMJE Other: BWT with Mitomycin-C prior TURBT
Participants will randomly assign, according to random computerized software, to those who receive the heated thermo-chemo therapy and those who will not. The intravesical instillation will take place up to 6 hours prior TURBT in the following matter: The "Elmedical" BWT system will introduce intravesically a 40mg of heated Mitomycin MMC, diluted in 50cc of saline at a uniform temperature (44-44.50C). The length of the procedure - 50 minutes
Other Name: Bladder wall thermo-chemotherapy (BWT)
Study Arms  ICMJE
  • No Intervention: TURBT ONLY

    A total of 150 patients in this arm will be divided into five follow-up sub groups according to pathology reports.

    Group 1 - Primary Low risk patients Group 2 - Primary Intermediate risk patients Group 3 - Primary High risk patients Group 4 - Recurrent Intermediate risk patients Group 5 - Recurrent Intermediate risk patients

  • Experimental: BWT with Mitomycin-C prior TURBT

    A total of 150 patients in this arm will be divided into five follow-up sub groups according to pathology reports.

    Group 1 - Primary Low risk patients Group 2 - Primary Intermediate risk patients Group 3 - Primary High risk patients Group 4 - Recurrent Intermediate risk patients Group 5 - Recurrent Intermediate risk patients

    Intervention: Other: BWT with Mitomycin-C prior TURBT
Publications * Di Stasi SM, Valenti M, Verri C, Liberati E, Giurioli A, Leprini G, Masedu F, Ricci AR, Micali F, Vespasiani G. Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial. Lancet Oncol. 2011 Sep;12(9):871-9. doi: 10.1016/S1470-2045(11)70190-5. Epub 2011 Aug 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 10, 2015)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2019
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult patients (>18 yrs.) with good performance status according to Eastern Cooperative Oncology Group (ECOG) scale, designed to TURBT and gave their consent to participate in our research.
  2. All participants must have adequate blood tests (CBC, Creatinine, electrolytes and liver function tests).

Exclusion Criteria:

  1. Concurrent other malignancy in the urinary system (e.g. upper tract UC)
  2. Urothelial malignancy of the bladder other then carcinoma
  3. Diffuse carcinoma in situ on preliminary cystoscopy
  4. Allergy or sensitivity to MMC
  5. Known urinary bladder capacity of less then 200cc
  6. Concurrent complicated urinary infection
  7. Autoimmune disease or patient under immunosuppressive therapy
  8. presence of urethral stricture
  9. Previous pelvic radiotherapy
  10. Concomitant malignancy of other organ
  11. Pregnancy
  12. Children under 18 years.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02471547
Other Study ID Numbers  ICMJE SHEBA-15-1760-JR-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof. Jacob Ramon, Sheba Medical Center
Study Sponsor  ICMJE Sheba Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jacob Ramon, Prof. Sheba Medical Center, Department od Urology
PRS Account Sheba Medical Center
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP