Clinical trial NCT02471547: Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT
Official title: Intravesically Heated Thermo-chemotherapy With Mitomycin-C Prior to TURBT- Prospective Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Transitional Cell Carcinoma
Keywords: Recurrence
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-06-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence rate of Urothelial carcinoma (UC) of bladder
timeFrame: Two years
Secondary outcomes:
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center, Department od Urology
name: Jacob Ramon, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.