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

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ClinicalTrials.gov Identifier: NCT02891460
Recruitment Status : Completed
First Posted : September 7, 2016
Last Update Posted : September 8, 2016
Sponsor:
Information provided by (Responsible Party):
UroGen Pharma Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Urologic Neoplasms Neoplasms Urinary Bladder Diseases Urologic Diseases Device: 40 mg MMC in 40 mL TC-3. Device: 80 mg MMC in 40 mL TC-3. Not Applicable

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2013
Actual Primary Completion Date : February 2014
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 40 mg MMC in 40 mL TC-3.
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.
Device: 40 mg MMC in 40 mL TC-3.
A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature) for drug retention in the urinary bladder.
Other Name: MMC-Gel

Experimental: 80 mg MMC in 40 mL TC-3.
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.
Device: 80 mg MMC in 40 mL TC-3.
A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature) for drug retention in the urinary bladder.
Other Name: MMC-Gel




Primary Outcome Measures :
  1. Subject's degree of response at 2-4 weeks post-treatment [ Time Frame: 9-11 weeks ]
    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

  2. Adverse events (AE) including serious adverse events (SAE) [ Time Frame: 1.2 years ]
  3. Anesthesia information [ Time Frame: 7 weeks ]
    Information of whether anesthesia was used during the treatment will be collected

  4. Blood and urine tests [ Time Frame: 9-11 weeks ]
    Blood and urine tests (including urine culture test) be be collected

  5. The degree of pain during treatment [ Time Frame: 7 weeks ]
    The degree of pain subject felt at the time the drug will be injected to the bladder will be collected (VAS)

  6. Gel clearance and urinary patency [ Time Frame: 7 weeks ]
    Data regarding gel clearance and adverse urinary patency post instillation will be obtained based on the "post instillation telephone follow-up" set of questions.


Secondary Outcome Measures :
  1. Tumor recurrence rate during 12 months post- 2-4 week follow-up visit in complete response (CR) subjects. [ Time Frame: 1.2 years ]
  2. Lesion Mass by time point (Screening and 2-4 weeks post-treatment) [ Time Frame: 9-11 weeks ]
    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


Other Outcome Measures:
  1. Subjects' satisfaction with the treatment [ Time Frame: 9-11 weeks ]
    Subjects' satisfaction with the treatment will be measured using an 8-item satisfaction questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion criteria:

  1. Single or multiple tumors (n≤7)
  2. Recurrent or Naive tumor.
  3. No prior history of T1 and/or Tis
  4. At least one tumor >1mm.
  5. Largest tumor diameter ≤ 30mm
  6. Cystoscopic appearance of papillary Low or high grade tumor

Main Exclusion Criteria:

  1. Carcinoma In Situ (CIS)
  2. Over 7 lesions
  3. Lesion is larger than 30mm in diameter
  4. Cystoscopic appearance suspicious for Tis
  5. Tumor located in prostatic urethra
  6. Previous systemic chemotherapy or pelvic radiotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02891460


Locations
India
Rajiv Gandhi Cancer Institute & Research Center
Delhi, New Delhi, India, 110085
Sponsors and Collaborators
UroGen Pharma Ltd.
Investigators
Principal Investigator: Sudhir Rawal, MD Rajiv Gandhi Cancer Institute & Research Center

Additional Information:
Responsible Party: UroGen Pharma Ltd.
ClinicalTrials.gov Identifier: NCT02891460     History of Changes
Other Study ID Numbers: TC-3 /2012 / P2
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: September 8, 2016
Last Verified: September 2016

Keywords provided by UroGen Pharma Ltd.:
Mitomycin C
MMC
NMIBC
Non Muscle Invasive Bladder Cancer
Hydrogel Reverse thermal gelation
Drug retention
Urinary Bladder Neoplasms
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases

Additional relevant MeSH terms:
Neoplasms
Urinary Bladder Neoplasms
Urologic Diseases
Urinary Bladder Diseases
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors