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The Efficacy and Safety of UGN-102 as a Primary Chemoablative Therapy in Patients With LG NMIBC at Intermediate Risk of Recurrence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03558503
Recruitment Status : Active, not recruiting
First Posted : June 15, 2018
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
UroGen Pharma Ltd.

Tracking Information
First Submitted Date  ICMJE May 8, 2018
First Posted Date  ICMJE June 15, 2018
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE October 25, 2018
Actual Primary Completion Date December 4, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2018)
Complete response (CR) rate for UGN-102 treatment [ Time Frame: 3 months after the first instillation of UGN-102 ]
To evaluate the tumor ablative effect of UGN-102 in patients with LG NMIBC
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Durable complete response (DCR) rate [ Time Frame: Six (6), nine (9), and Twelve (12) months after the first instillation of UGN-102 ]
    To evaluate the durability of response in patients with LG NMIBC who achieve CR
  • Incidence (number of patients) of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) incidence analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Frequency (number of events) of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) frequency analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Seriousness of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) seriousness analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Severity of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) severity analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Type of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) type analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Changes from baseline in laboratory values [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    Changes in laboratory values of hematology and serum chemistry which will be defined as potentially clinically meaningful will be reported as such (number of participants with potentially clinically meaningful laboratory values will be counted). Laboratory values will include the following : Complete blood count (CBC, including red blood cell indices and white blood cell differential Platelet count Creatinine Blood urea nitrogen Uric acid Sodium Potassium Phosphorus Calcium Bicarbonate Chloride SGOT/AST SGPT/ALT GGT Alkaline phosphatase Total bilirubin Direct bilirubin Albumin Total protein
  • Clinically meaningful changes in full physical examination [ Time Frame: Screening visit and Twelve (12) months after the first instillation of UGN-102 ]
    Changes in Full Physical Examination findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful Full Physical Examination findings will be counted). Full physical examination findings are composite outcome measure consisting of multiple measures: General appearance Cardiovascular system Respiratory system HEENT (head, eyes, ears, nose, and throat) and neck Abdomen Extremities Neurologic system Skin
  • Clinically meaningful changes Urology-Oriented Physical Examination [ Time Frame: First day of treatment and after 22 days and 3, 4, 5, 7, 8, 10, 11 and 12 months after the first instillation of UGN-102 ]
    Changes in Urology-Oriented Physical Examination findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful Urology-Oriented Physical Examination findings will be counted). Urology-Oriented physical examination findings are composite outcome measure consisting of multiple measures: Urethral meatus Perineal skin and mucus membranes Scrotum and testes (for male patients) Lymphadenopathy Rectal examination (male patients - Screening visit only) Bimanual examination (female patients - Screening visit only)
  • Clinically meaningful changes vital signs [ Time Frame: Screening visit and at each study visit until Twelve (12) months after the first instillation of UGN-102 ]
    Changes in vital signs findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful vital signs findings will be counted). . Vital signs are composite outcome measure consisting of multiple measures: Blood pressure, heart rate, respiration rate, and body temperature.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2018)
  • Durable complete response (DCR) rate [ Time Frame: Six (6), nine (9), and Twelve (12) months after the first instillation of UGN-102 ]
    To evaluate the durability of response in patients with LG NMIBC who achieve CR
  • Incidence (number of patients) of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) incidence analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Frequency (number of events) of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) frequency analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Seriousness of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) seriousness analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Severity of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) severity analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Type of adverse events [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    AE (Adverse Events) type analyses will include both all AEs and treatment emergent AEs (TEAEs), i.e., events that started on the day of first administration of study medication or afterwards, or were present before first administration of study medication and increased in intensity after first administration of study medication. Listings of both TEAEs and non-TEAES will be provided.
  • Changes from baseline in laboratory values [ Time Frame: From the time a patient has signed the informed consent until 30 days after the last instillation of study medication ]
    Changes in laboratory values of hematology and serum chemistry which will be defined as potentially clinically meaningful will be reported as such (number of participants with potentially clinically meaningful laboratory values will be counted). Laboratory values will include the following : Complete blood count (CBC, including red blood cell indices and white blood cell differential Platelet count Creatinine Blood urea nitrogen Uric acid Sodium Potassium Phosphorus Calcium Bicarbonate Chloride SGOT/AST SGPT/ALT GGT Alkaline phosphatase Total bilirubin Direct bilirubin Albumin Total protein
  • Clinically meaningful changes in full physical examination [ Time Frame: Screening visit and Twelve (12) months after the first instillation of UGN-102 ]
    Changes in Full Physical Examination findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful Full Physical Examination findings will be counted). Full physical examination findings are composite outcome measure consisting of multiple measures: General appearance Cardiovascular system Respiratory system HEENT (head, eyes, ears, nose, and throat) and neck Abdomen Extremities Neurologic system Skin
  • Clinically meaningful changes Urology-Oriented Physical Examination [ Time Frame: First day of treatment and after 22 days and 3, 4, 5, 7, 8, 10, 11 and 12 months after the first instillation of UGN-102 ]
    Changes in Urology-Oriented Physical Examination findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful Urology-Oriented Physical Examination findings will be counted). Urology-Oriented physical examination findings are composite outcome measure consisting of multiple measures: Urethral meatus Perineal skin and mucus membranes Scrotum and testes (for male patients) Lymphadenopathy Rectal examination (Screening visit only) Bimanual examination (female patients - Screening visit only)
  • Clinically meaningful changes vital signs [ Time Frame: Screening visit and at each study visit until Twelve (12) months after the first instillation of UGN-102 ]
    Changes in vital signs findings which will be defined as clinically meaningful will be reported as such (number of participants with clinically meaningful vital signs findings will be counted). . Vital signs are composite outcome measure consisting of multiple measures: Blood pressure, heart rate, respiration rate, and body temperature.
Current Other Pre-specified Outcome Measures
 (submitted: November 8, 2018)
  • Plasma Mitomycin C concentration [ Time Frame: Plasma Mitomycin C concentration will be assessed pre-instillation, 0.5, 1, 2, 3, 4, 5, and 6 hours post the first instillation. ]
    Plasma Mitomycin C concentration will be assessed in a sub-group set of 6 patients treated with UGN-102 .
  • Plasma Mitomycin C area under the curve (AUC) [ Time Frame: Plasma Mitomycin C AUC be assessed pre-instillation, 0.5, 1, 2, 3, 4, 5, and 6 hours post the first instillation. ]
    Plasma Mitomycin C AUC will be assessed in a sub-group set of 6 patients treated with UGN-102 .
  • Plasma Mitomycin C maximum concentration (Cmax) [ Time Frame: Plasma Mitomycin C Cmax be assessed pre-instillation, 0.5, 1, 2, 3, 4, 5, and 6 hours post the first instillation. ]
    Plasma Mitomycin C Cmax will be assessed in a sub-group set of 6 patients treated with UGN-102 .
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Efficacy and Safety of UGN-102 as a Primary Chemoablative Therapy in Patients With LG NMIBC at Intermediate Risk of Recurrence
Official Title  ICMJE A Phase 2b, Single-Arm, Multicenter Trial to Evaluate the Efficacy and Safety of UGN-102 as Primary Chemoablative Therapy in Patients With Low Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk of Recurrence
Brief Summary The study is investigating the efficacy and safety of UroGen's UGN-102 to treat patients with Low Grade (LG) Non Muscle Invasive Bladder Cancer (NMIBC) at intermediate risk of recurrence.
Detailed Description

This study is a prospective, open-label, single-arm, multicenter Phase 2b trial designed to assess the efficacy and safety of UGN-102 treatment instilled in patients diagnosed with LG NMIBC, including newly diagnosed patients, and determined to have intermediate risk of progression, defined as 1 or 2 of the following: multiple tumors, solitary tumor >3 cm, or recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis). Eligible patients will be treated with 6 weekly instillations of UGN-102.

UGN-102 is a reverse thermal hydrogel formulated with MMC. The product is specifically formulated to achieve a liquid state at 4°C and to transition to a water-soluble gel at body temperature. The advantage of delivering Mitomycin to the urinary bladder using UGN-102 relies on preclinical and clinical literature documenting that concentration and dwell time correlate directly with the therapeutic efficacy of MMC when used to treat Urothelial Carcinoma (UC)

The ablative effect of UGN-102 will be evaluated at the Primary Disease Evaluation (3 MONTH) assessment, which will take place 5 weeks ±1 week after the last weekly instillation (3 months after initiation of study medication). Response will be determined based on visual evaluation by cystoscopy (appearance, number, size, and location of the lesions) and, if there are remaining lesions, by histopathology of the remaining lesions. CR is defined as having no detectable disease (NDD) and will be assessed visually during cystoscopy and also upon urine cytology. In the event that the investigator is not sure, and there is suspect tissue, a small biopsy will be taken from the suspect tissue to confirm CR in addition to cystoscopy and urine cytology. Patients who achieve a CR will continue to have monthly telephone contacts to document any adverse events and changes in concomitant medications and will be assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence of disease recurrence. The group of patients considered nonresponders (non-CR) will discontinue the study and continue with standard of care according to their treating physician.

Safety will be determined based on physical examination, laboratory assessments, and a review of AEs. All safety data will be reviewed on an ongoing basis, including close review and follow up of any unexpected AE related to UGN-102 and qualified per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) as Grade 3 or 4.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bladder Cancer
  • Urothelial Carcinoma
  • Urothelial Carcinoma Bladder
Intervention  ICMJE Drug: UGN-102
Six (6) intravesical instillations of UGN-102 (1.33 mg) will be given weekly.
Other Name: MMC + UG-1 gel
Study Arms  ICMJE Experimental: UGN-102
75 mg Mitomycin C (MMC) in 56 mL admixture (1.33 mg MMC per 1 mL of admixture).
Intervention: Drug: UGN-102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 12, 2019)
63
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2018)
60
Estimated Study Completion Date  ICMJE November 2020
Actual Primary Completion Date December 4, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. ≥ 18 years of age.
  2. Willing and able to sign an informed consent and comply with the protocol.
  3. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 6 weeks of screening
  4. Is at intermediate risk for progression, defined as having 1 or 2 of the following:

    1. presence of multiple tumors,
    2. solitary tumor >3 cm
    3. recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis).
  5. Has negative voiding cytology for HG disease at or within 6 weeks of enrollment.
  6. Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the female partner is of childbearing potential (defined as premenopausal women who have not been sterilized).
  7. Has adequate organ and bone marrow function as determined by routine laboratory tests as below:

    Leukocytes ≥3,000/μL (≥3×109/L), Absolute neutrophil count ≥1,500/μL (≥1.5×109/L), Platelets ≥100,000/μL (≥100×109/L), Hemoglobin ≥9.0 mg/dL, Total bilirubin ≤1.5 upper limit of normal (ULN), AST (SGOT)/ALT (SGPT) ≤2.5 × upper limit of normal (ULN), ALP ≤2.5 × ULN, and Estimated glomerular filtration rate (eGFR) ≥30 mL/min.

  8. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline visits.

In the case of symptomatic UTI, the patient will be treated with a full course of antibiotics, and study medication will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study medication is left to the discretion of the Principal Investigator (PI).

Exclusion Criteria:

  1. History of Carcinoma in Situ (CIS) on preliminary cystoscopy within 5 years of enrollment.
  2. Received Bacillus Calmette-Guérin (BCG) treatment for UC within previous 2 years.
  3. History of HG papillary UC in the past [2] years
  4. Known allergy or sensitivity to mitomycin.
  5. Clinically significant urethral stricture that would preclude passage of a urethral catheter.
  6. History of pelvic radiotherapy.
  7. History of:

    1. neurogenic bladder
    2. active urinary retention
    3. any other condition that would prohibit normal voiding
  8. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic UC or concurrent upper tract urothelial carcinoma (UTUC).
  9. Has participated in a study with an investigational agent or device within 30 days of enrollment.
  10. History of prior treatment with an intravesical chemotherapeutic agent with the exception of a single dose of chemotherapy immediately post-TURBT.
  11. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03558503
Other Study ID Numbers  ICMJE TC-BC-12
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party UroGen Pharma Ltd.
Study Sponsor  ICMJE UroGen Pharma Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Robert, MS, CNS, CCRC UroGen pharma Inc
Study Director: Nimrod Gabai, BSc UroGen pharma Inc
PRS Account UroGen Pharma Ltd.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP