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Trial record 24 of 26 for:    upper tract urothelial

Efficacy and Safety of UGN-101 in Recurrent Patients (Retreatment)

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ClinicalTrials.gov Identifier: NCT04006691
Recruitment Status : Recruiting
First Posted : July 3, 2019
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
UroGen Pharma Ltd.

Brief Summary:
This trial is designed to evaluate the efficacy and safety of UGN-101 administered to the upper urinary tract (UUT) in patients who were treated in Trial TC-UT-03, found to be a complete response (CR) at the Primary Disease Evaluation (PDE) 1 Visit and are subsequently found to have a documented recurrence of low grade (LG) upper tract urothelial carcinoma (UTUC) at follow up (FU).

Condition or disease Intervention/treatment Phase
Carcinoma Transitional Cell Carcinoma Transitional Cell Cancer of the Renal Pelvis and Ureter Drug: UGN-101 instillations Phase 3

Detailed Description:

This is an open-label, single-arm, Phase 3b multicenter extension trial, designed to evaluate the efficacy and safety of UGN-101 administered to the UUT in patients who were treated in Trial TC-UT-03, found to be a CR at the PDE 1 Visit, and are subsequently found to have a documented recurrence of LG UTUC at FU.

Upon signing of informed consent, the patients will undergo their routine ureteroscopy to assess durability. A biopsy will be performed at Visit 0, if appropriate, to confirm evidence of tumor. If a high grade (HG) UTUC is confirmed by biopsy and/or cytology, the patient will be excluded from the retreatment trial. Eligible patients with confirmed LG non-invasive UTUC will be treated with 3 to 6 once-weekly instillations of UGN-101 in a retrograde fashion, per investigator's discretion.

Five weeks (± 1 week) following the last Investigational product (IP) treatment, the patient will be assessed for efficacy and safety at the PDE 2 Visit. At this visit, the patient will undergo ureteroscopy and any remaining lesions will be biopsied, and UUT urine wash will be collected for cytology.

Patients demonstrating CR at the PDE 2 Visit will undergo FU visits at 3, 6, 9, and 12 months (± 2 weeks) following the PDE 2 Visit.

The trial will be approximately 15 months, per patient: a 3- to 6-week treatment period, followed by 4 to 6 weeks post-treatment leading up to the PDE 2 Visit, and a 12-month FU post PDE 2 Visit. This trial will follow the Steering Committee, and a Data Monitoring Committee (DMC) has been assigned as established for the primary trial TC-UT-03.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b Multicenter Extension Trial Evaluating the Efficacy and Safety of UGN-101 (Mitomycin Gel) for Instillation on Ablation of Upper Urinary Tract Urothelial Carcinoma in Recurrent Patients From Trial TC-UT-03
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : December 16, 2020
Estimated Study Completion Date : December 16, 2021


Arm Intervention/treatment
Experimental: UGN-101 instillations
The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, the maximum dose is 15ml. 3-6 once weekly intravesical instillations for the ablation treatment.
Drug: UGN-101 instillations
Treatment with UGN-101 once weekly for a total of 3-6 times; in a retrograde fashion.
Other Names:
  • UGN-101
  • MitoGel™




Primary Outcome Measures :
  1. Complete response (CR) rate [ Time Frame: An average of 11 weeks ]
    Complete response defined dichotomously as "Success" if CR was confirmed at the end of the treatment period (PDE 2 Visit), and "Failure" otherwise.


Secondary Outcome Measures :
  1. Long-term durability of complete response (CR) [ Time Frame: 3, 6, 9 and 12 months ]
    This endpoint is defined only for those patients demonstrating CR at the PDE 2 Visit.


Other Outcome Measures:
  1. Incidence (number of patients) of adverse events [ Time Frame: 15 months ]

    Adverse events (AEs) analyses will include only Treatment Emergent Adverse Events (TEAEs), namely, those events which started on the day of first trial IP administration or afterwards.

    The incidence (no. of patients) of TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary;

    • Breakdowns of TEAEs by all AEs attributes will also be provided;
    • Breakdowns of TEAEs by age, sex and volume of instillation will also be provided;
    • The incidence of serious TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary as well as by serious adverse events (SAEs) attributes and by age, sex, and volume of instillation. SAEs will also be listed.

  2. Frequency (number of events) of adverse events [ Time Frame: 15 months ]

    Adverse events (AEs) analyses will include only Treatment Emergent Adverse Events (TEAEs), namely, those events which started on the day of first trial IP administration or afterwards.

    The Frequency (no. of patients) of TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary;

    • Breakdowns of TEAEs by all AEs attributes will also be provided;
    • Breakdowns of TEAEs by age, sex and volume of instillation will also be provided;
    • The Frequency of serious TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary as well as by serious adverse events (SAEs) attributes and by age, sex, and volume of instillation. SAEs will also be listed.

  3. Clinically meaningful changes in laboratory values of blood hematology, coagulation, liver and kidney function parameters and urinalysis [ Time Frame: 15 months ]

    Changes from baseline in laboratory values and incidence of measurements defined as Potentially Clinically Significant (PCS) 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, serum glutamate oxaloacetate transaminase/aspartate aminotransferase (SGOT/AST), serum glutamate pyruvate transaminase/Alanine transaminase (SGPT/ALT), gamma-glutamyl transferase (GGT), Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Albumin, Total protein, Prothrombin Time and International Normalized Ratio, and Urinalysis (Specific gravity, power of hydrogen (pH), Glucose, Urobilinogen, Bilirubin, Blood, Protein, Nitrites, Leukocyte Esterase, Microscopic examination, Bacteriuria (if required) and White blood cells)


  4. Clinically meaningful changes in vital signs assessments values (blood pressure, pulse and temperature) [ Time Frame: 15 months ]
    Changes from baseline in vital signs assessments values and incidence of measurements of Potential Clinical Significance (PCS) will include blood pressure, pulse, and temperature

  5. Clinically meaningful changes in full physical examination values including General appearance, Cardiovascular and Respiratory system, HEENT (head, eyes, ears, nose, and throat) and neck, Abdomen Extremities, Neurologic system, Skin and Urological system [ Time Frame: 15 months ]

    Any clinically-relevant changes occurring during the trial visit will be recorded in the AE sections of the case report form (CRF). Full general physical examination will be done on visits 0, 7, and 11 Urology-oriented physical examinations will be done on visits 0, 7, 8, 9, 10, and 11.

    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 and Neurologic system Skin

    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)




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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. Patients with recurrent LG UTUC who were found to be CR at the PDE 1 Visit (in Trial TC-UT-03).
  2. Biopsy taken from 1 or more tumors located in the UUT shows LG urothelial carcinoma (up to 2 months before Visit 0). If there are tumors in both the kidney and the ureter, at least 1 biopsy should be taken from each location.
  3. Urine wash cytology sampled from the UUT documenting the absence of HG urothelial cancer.
  4. Patients must have adequate organ and bone marrow function as determined by routine laboratory tests.
  5. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis

Main Exclusion Criteria:

  1. Patient intends to be treated with systemic chemotherapy during the duration of the trial.
  2. Patient with urinary obstruction.
  3. Inability to deliver the IP to the UUT.
  4. Patient has any other medical or mental condition(s) that make(s) their participation in the trial unadvisable in the opinion of the treating investigator.
  5. Patient has a contraindication to mitomycin treatment, or known sensitivity to mitomycin.

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): NCT04006691


Contacts
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Contact: Madlen Malinowski 1-646-768-9533 Madlen.Malinowski@urogen.com
Contact: Ifat Klein, Phd +972-9-770-7629 Ifat.Klein@urogen.com

Locations
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United States, California
UCLA - University of California, Los Angeles Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Chamie Karim, MD    310-206-8183    kchamie@mednet.ucla.edu   
Contact    (310)794-5929      
United States, Florida
Mayo Clinic Florida Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Raymond Pak, M.D.    404-683-5298    Pak.Raymond@mayo.edu   
Contact: Katie Custer       Custer.Kaitlynn@mayo.edu   
United States, Maryland
John Hopkins University Not yet recruiting
Baltimore, Maryland, United States, 21218
Contact: Phillip Pierorazio, MD    410-955-6850    philpierorazio@jhmi.edu   
United States, Nevada
Urology Center Las Vegas Recruiting
Las Vegas, Nevada, United States, 89144
Contact: Michael Verni, M.D.    702-212-3428    mverni@mac.com   
Contact: Danielle Freedman       drfreedman@msn.com   
Israel
Sheba Medical Center Not yet recruiting
Ramat Gan, Israel, 52621
Contact: Nir Kleinmann, M.D.    952-53-3398845    nir.kleinmann@gmail.com   
Contact: Efrat Levi    972-3-5304736    Efrat.Ezra@sheba.health.gov.il   
Sponsors and Collaborators
UroGen Pharma Ltd.
Investigators
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Study Director: Ifat Klein, Phd UroGen Pharma

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Responsible Party: UroGen Pharma Ltd.
ClinicalTrials.gov Identifier: NCT04006691     History of Changes
Other Study ID Numbers: TC-UT-03/E
First Posted: July 3, 2019    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UroGen Pharma Ltd.:
Upper Tract
TC-3
MitoGel
UGN-101
UTUC
Ureteral
Carcinoma
Kidney
Renal
Ureter
Gel
Local
Mitomycin C
Prolonged Release
Slow Release
Kidney Sparing
T1
T0
Low Grade
Transitional Cell Carcinoma of Renal Pelvis
TCC
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors