Clinical trial NCT01803295: Pre-TURBT TC-3 Gel Intravesical Instillation in NMIBC
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Carcinoma of Urinary Bladder, Superficial
Keywords: Non Muscle Invasive Bladder Cancer
Intravesical instillation
Mitomycin C
Hydrogel Reverse thermal gelation
Drug retention
Urinary Bladder Neoplasms
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycin
Lead sponsor: UroGen Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2013-03-04
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

1. Patient is 21 years of age or older.
2. Patient has signed Informed Consent Form and is willing and able to abide by the protocol.
3. Naïve or recurrent low grade (LG) NMIBC tumor
4. Recurrent patients - Single or multiple tumors
5. Naive patients - 2 tumors or above
6. No prior history of HG and/or T1 in the past 5 years.
7. No prior history of Tis
8. At least one Tumor ≥ 1 mm as evaluated visually by the investigator.
9. Largest tumor diameter ≤ 30 mm as evaluated visually by the investigator
10. Cystoscopic appearance of papillary Low grade tumor
11. No active urinary tract infection as confirmed by urine culture
12. If the patient is a female of childbearing potential , she is using two acceptable \& effective methods of contraception , until 6 months post treatment
13. If the patient is a male he should use a condom during intercourse, for at least 48 hours post each instillation
14. If the patient is a male that has a partner that is a female of childbearing potential, he should be advised to use two acceptable \& effective methods of contraception until 6 months post treatment.

Exclusion Criteria:

1. Carcinoma In Situ (CIS).
2. "High Grade" urine cytology which is conclusive for HG.
3. "High Grade" tumor results in cold cup biopsy.
4. Tumor located in prostatic urethra.
5. Previous systemic chemotherapy in the last 2 years or pelvic radiotherapy.
6. Pregnant or breastfeeding patient.
7. Previous treatment with BCG within the last 12 months.
8. The patient did not have at least 3 months cystoscopically confirmed tumor-free interval between the last TURBT to current tumor recurrence.
9. Treatment with full course of intravesical chemotherapy within the 3 last months.
10. The patient has/had any bladder tumor with histology other than TCC.
11. Known contraindication or hypersensitivity to MMC or gel.
12. The patient has a known history of upper urinary tract urothelial carcinoma, or Renal Cell carcinoma or other renal cancer.
13. The patient has a known urinary retention which, according to the investigator's opinion, might lead to avoid patient receiving the treatment.
14. The patient has a bleeding disorder or a screening platelet count \<50X109/L.
15. The patient has screening hemoglobin \<10 mg/dL.
16. The patient has a condition or a concurrent severe and/or uncontrolled medical or psychiatric disease (e.g. uncontrolled diabetes, compensated congestive heart failure (NYHA III and over), myocardial infarction within 6 months of study, unstable or uncontrolled hypertension or an active uncontrolled infection), which could compromise participation, compliance with scheduled visits and/or completion.
17. The patient participated in an investigational interventional study within the past 90 days.
18. The patient has documented sever vesico-ureteral reflux or an indwelling ureteral stent.
19. The patient has the tumor in the bladder diverticulum.
20. The patient participated in a prior TheraCoat's trial with MMC and TC-3

Primary outcomes:
measure: ablative effect of pre-TURBT intravesical instillations of the treatments on The bladder lesion(s) of NMIBC patients
timeFrame: 2 years
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability rate.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
measure: Comparison of the cystoscopic and pathological effect between the 2 groups.
timeFrame: 2 years
measure: • Comparison of one year tumor recurrence rate between both treatment groups
timeFrame: 2 years
measure: • 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
timeFrame: 1 year
Locations:
city: Haifa
country: Israel
facility: Carmel Medical Center of Haifa, Department of Urology
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Holon
country: Israel
facility: Wolfson Medical Center of Holon, Department of Urology
city: Kfar Saba
country: Israel
facility: Meir medical center
city: Nahariya
country: Israel
facility: Galil Maaravi Medical Center of Nahariya, Department of Urology
city: Petach Tikvah
country: Israel
facility: Rabin Medical Center of Petah Tikva, Department of Urology
city: Zefat
country: Israel
facility: Ziv Medical Center
city: Milan
country: Italy
facility: Vita Salute University, San Raffaele Hospital of Milan, Department of Urology
city: Rome
country: Italy
facility: S. Andrea Hospital of Rome, Department of Urology
city: Salerno
country: Italy
facility: Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofìa of Madrid, Department of Urology
city: Geneva
country: Switzerland
facility: Hôpital HUG of Geneva, Department of Urology
Study officials:
affiliation: Radboud University Nijmegen Medical Centre, Department of Urology Geert Grooteplein South 10 (659), Nijmegen
name: Fred Witjes, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Tübingen Universitätsklinik für Urologie
name: Stenzl, Prof.
role: PRINCIPAL_INVESTIGATOR
References: