Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urologic Diseases

Urinary Bladder Diseases

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

120 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel

120 mg MMC in 90ml gel

140 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel

140 mg MMC in 90ml gel

160 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel

160 mg MMC in 90ml gel

120 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel

120 mg MMC in 60ml gel

140 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel

140 mg MMC in 60ml gel

160 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel

160 mg MMC in 60ml gel

Ifat Klein, PhD

A prospective, open label, modified 3+3 dose escalation study. This dose-escalation study is designed to carefully assess the safety of successive cohorts of patients (3 patients/cohort), each cohort treated with a fixed dose of TC-3 and MMC Intravesical instillations.

A prospective, open label, modified 3+3 dose escalation study. This dose-escalation study is designed to carefully assess the safety of successive cohorts of patients. A total of 10 patients will be treated in the first cohort with 120mg MMC-TC-3 Gel unless DLT is reached in more than 1/3 of the patients in the cohort. The next cohorts will have 3 patients/cohort, each cohort treated with a fixed dose of TC-3 and MMC Intravesical instillations. Since data is already available for 40 and 80 mg MMC in TC-3 gel, the initial cohort is 120mg MMC mixed with of 60 mL TC-3. Subsequent cohorts will be given dose levels of 140mg \& 160mg MMC mixed with 60 mL TC-3. Thus, if 160mg MMC mixed in 60ml TC-3 will be found to be safe and tolerable, no higher doses will be further explored at this stage.

If 120 mg MMC in 60 ml TC-gel (2 mg/ml) is found to be intolerable, higher concentrations will not be tested. Instead, a dose of 120 mg in 90 cc TC gel and a subsequent doses of 140 and 160 mg MMC in 90 cc TC gel will be tested in the same dose escalating manner. This will allow testing similar doses at lower concentrations (up to 1.78 mg/ml) but with a longer dwell time due to the larger volume of TC-gel.

Dose escalation is to be halted when the maximum tolerated dose (MTD) will be reached; MTD is defined as one dose level below which dose limited toxicity (DLT) is Any adverse event (AE) related to TC-3+MMC and qualified per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) as grade 3 or 4 will be evaluated by board of 2 independent physicians to determine if it qualifies as DLT based on the known safety profile of MMC. If the NCI grade will not apply, the adverse event to be graded as mild, moderate, or severe.

If one of the three patients in a cohort experienced a DLT, three more patients will be added to the cohort for AE confirmation, only if 3 patients from the given cohort will experienced DLT, the MTD will be reached If no further DLTs are observed in the cohort, the three patients will be enrolled in the next successive cohort.

Safety of Pre-TURBT Intravesical Instillation of Escalating Doses of TC-3 Gel and MMC in NMIBC Patients

Evaluation of the Safety of Pre-TURBT Intravesical Instillation of Escalating Doses of TC-3 Gel Mixed With Mitomycin C (MMC) in Non-muscle Invasive Bladder Cancer (NMIBC) Patients

Complete Response (CR) rate defined as percent of patients with CR at the Primary Disease Evaluation (PDE) Visit

Durable Complete Response (CR) rate defined as percent of patients who continue to display CR at 3, 6, 9 and 12 months following the last treatment.

UroGen Pharma Ltd.

TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 40 ml of TC-3 gel mixed with 40 mg MMC will be instilled using catheter.

TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 40 ml of TC-3 gel mixed with 80 mg MMC will be instilled using catheter.

A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature) for drug retention in the urinary bladder.

40 mg MMC in 40 mL TC-3.

80 mg MMC in 40 mL TC-3.

Sudhir Rawal, MD

The purpose of this study is to evaluate the clinical response of the tumors within the bladder of recurrent NMIBC patients to Mitomycin-C embedded in UroGen Pharma's (known at that time as TheraCoat Ltd.) TC-3 Sterile Hydrogel (TC-3) and to evaluate the patency of ureters 6 hr post instillation.

An open label, successive dose escalation trial in subjects with Non Muscle Invasive Bladder Cancer (NMIBC), designed to evaluate the clinical response of low-intermediate risk tumors within the bladder to Mitomycin-C embedded in TC-3 Sterile Hydrogel (TC-3), administered intravesically, prior to TURBT in NMIBC subjects.

Eligible subjects with NMIBC will be recruited to the trial following the initial diagnostic cystoscopy. During the diagnostic cystoscopy, the number of tumor lesions, their size and location will be documented and recorded with video or photo cystoscopy.

A baseline cystoscopy will be conducted in all subjects for the evaluation of number of tumors and their diameters, and for mapping of their location. Baseline blood samples for liver and renal functions, as well as for complete blood count (CBC) and coagulation tests will be drawn prior to instillation to ensure eligibility and to serve as a reference point for systemic safety follow-up.

A future TURBT has been planned for 8-10 weeks post screening. Enrolled subjects will be treated successively with 40mg MMC in 40 mL TC-3 (the first 6 subjects) and with 80 mg MMC in 40 mL TC-3 (the following 12 subjects). At treatment session initiation, an 18-20 Fr two-way catheter will be inserted into the subject's bladder in order to completely empty the bladder of urine. Thereafter, a volume of 40 mL of cooled TC-3 mixed with 40 mg or 80 mg of MMC will be instilled through the catheter into the bladder of the subject. The catheter will then be ligated for twenty minutes, after which it will be drawn out of the bladder and the subject was will be allowed to urinate freely.

The subjects will undergo six weekly bladder instillations according to their assigned treatment of either 40 mg MMC (Group A) or 80 mg MMC (Group B) in 40 mL of TC-3. Following completion of instillation treatment series, there will be a 2-4 weeks healing period prior to next follow up visit (overall 10-12 weeks post screening). During 2-4 weeks follow-up (FU) visit, the lesions' status will be examined under cystoscopy. For subjects who will appear to have complete response (CR), this will be confirmed based on histological results. For subjects that will not be classified as having CR, decision about performance of TURBT or giving additional treatment will be at the PI's discretion.

Following 2-4 week FU visit, subjects will be managed according to their local standard guidelines. All patients will attempt to be followed up for 12 months following 2-4 weeks FU within the trial. These visits will be documented and data regarding recurrence and progression will be collected. Moreover, biopsy slides prior (when available), and following treatment will be collected and analyzed by an independent uro-pathologist.

Pilot Study to Evaluate the Clinical Response to Mitomycin-C in Hydrogel (TC-3) Administered Intravesically in NMIBC Patients

Evaluation of the Clinical Response of Mitomycin-C (MMC) Embedded in Hydrogel (TC-3) in Comparison to Mitomycin C in Saline, When Administered Intravesically, Pre-TURBT in Non Muscle Invasive Bladder Cancer (NMIBC) Patients. Muscle Invasive Bladder Cancer (NMIBC) Patients

Subjects' satisfaction with the treatment will be measured using an 8-item satisfaction questionnaire

Cystoscopic and pathological effect of pre-TURBT intravesical instillations with 40 or 80 mg of MMC mixed with 40cc TC-3 Hydrogel on bladder lesion(s) of NMIBC patients

Information of whether anesthesia was used during the treatment will be collected

Blood and urine tests (including urine culture test) be be collected

The degree of pain subject felt at the time the drug will be injected to the bladder will be collected (VAS)

Data regarding gel clearance and adverse urinary patency post instillation will be obtained based on the "post instillation telephone follow-up" set of questions.

Lesion mass will consider the number and size of the papillary lesion, and will be described at Screening and in 2-4 weeks follow-up visit

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety of Pre-TURBT Intravesical Instillation of Escalating Doses of TC-3 Gel and MMC in NMIBC Patients	NCT02307487	Bladder Cancer Neoplasms Urinary Bladder... Urologic Diseas...	120 mg MMC in 9... 140 mg MMC in 9... 160 mg MMC in 9... 120 mg MMC in 6... 140 mg MMC in 6... 160 mg MMC in 6...	18 Years -	UroGen Pharma Ltd.
Pilot Study to Evaluate the Clinical Response to Mitomycin-C in Hydrogel (TC-3) Administered Intravesically in NMIBC Patients	NCT02891460	Urinary Bladder... Urologic Neopla... Neoplasms Urinary Bladder... Urologic Diseas...	40 mg MMC in 40... 80 mg MMC in 40...	18 Years -	UroGen Pharma Ltd.

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