NCT02307487

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: UroGen Pharma Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Bladder Cancer
• Neoplasms
• Urinary Bladder Diseases
• Urologic Diseases

Interventions

Type	Name	Description
DRUG	120 mg MMC in 90ml gel	120 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel
DRUG	140 mg MMC in 90ml gel	140 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel
DRUG	160 mg MMC in 90ml gel	160 mg of Mitomycin C mixed with 90 ml UroGen's TC-3 gel
DRUG	120 mg MMC in 60ml gel	120 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel
DRUG	140 mg MMC in 60ml gel	140 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel
DRUG	160 mg MMC in 60ml gel	160 mg of Mitomycin C mixed with 60 ml UroGen's TC-3 gel

Timeline

• Start date: 2014-12-01
• Primary completion: 2016-04-01
• Completion: 2017-06-01
• First posted: 2014-12-04
• Last updated: 2017-06-16

Locations

2 sites across 1 country: Israel