Mitomycin (formulation contains poloxamer 407 excipient) for Non-muscle invasive bladder cancer

Inclusion criteria

• {"criterion_text":"- 1. Provide written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol."}
• {"criterion_text":"- 2. Patient must be ≥ 18 years of age at the time of informed consent."}
• {"criterion_text":"- 3. Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. Note: This is a diagnostic biopsy to demonstrate histopathology of tumor and resection of the tumor is not to be performed. Residual tumor must be present and documented after biopsy and before instillation of study treatment."}
• {"criterion_text":"- 4. History of at least 1 prior episode of NMIBC. Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened."}
• {"criterion_text":"- 5. Has intermediate risk disease, defined as having 1 or 2 of the following: a. Presence of multiple tumors. b. Solitary tumor > 3 cm. c. Early or frequent recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial Screening Visit) Note: Patients with all 3 factors are considered high risk and are not eligible to participate."}
• {"criterion_text":"- 6. Negative voiding cytology for HG disease within 8 weeks before Screening"}
• {"criterion_text":"- 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 g/dL. • Total bilirubin ≤ 1.5 × ULN. • AST and ALT ≤ 2.5 × ULN. • ALP ≤ 2.5 × ULN. • eGFR ≥ 30 mL/min."}
• {"criterion_text":"- 8. Has an anticipated life expectancy of at least the duration of the trial."}
• {"criterion_text":"- 9. Both male and female patients: Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female partner of male patient: 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). Acceptable methods of birth control which are considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only hormonal), condoms with spermicide, sexual abstinence* or vasectomized partner. * Sexual abstinence is defined as refraining from intercourse from enrollment through 6 months post treatment. Periodic abstinence (calendar, symptothermal, postovulation methods) is NOT an acceptable method of contraception. b. Female patient: Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the patient is of childbearing potential (defined as premenopausal women who have not been sterilized)"}

Exclusion criteria

• {"criterion_text":"- 1. Received BCG treatment for UC within the previous 1 year."}
• {"criterion_text":"- 10. Is pregnant or breastfeeding"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 12. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous TURBT"}
• {"criterion_text":"- 13. Has participated in a study with an investigational agent or device within 30 days of enrollment"}
• {"criterion_text":"- 14. Has previously participated in a study in which they received UGN-102"}
• {"criterion_text":"- 15. Has any other active malignancy requiring treatment with systemic anticancer therapy (eg, chemotherapy, immunotherapy, radiation therapy). Superficial cancers such as cutaneous basal cell or squamous cell carcinomas that can be treated locally are allowed."}
• {"criterion_text":"- 16. Has any other clinically significant medical or surgical condition that in the investigator’s opinion could compromise patient safety or the interpretation of study results"}
• {"criterion_text":"- 17. Where applicable per country regulation, the patient must not be currently committed to an institution by virtue of an order issued by either judicial or administrative authorities"}
• {"criterion_text":"- 2. History of HG bladder cancer (papillary or CIS) in the past 2 years"}
• {"criterion_text":"- 3. Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator’s opinion cannot be readily managed"}
• {"criterion_text":"- 4. Clinically significant urethral stricture that would preclude passage of a urethral catheter"}
• {"criterion_text":"- 5. History of: a. Neurogenic bladder. b. Active urinary retention. c. Any other condition that would prohibit normal voiding"}
• {"criterion_text":"- 6. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC"}
• {"criterion_text":"- 7. Current tumor staging of T1"}
• {"criterion_text":"- 8. Concurrent UTUC"}
• {"criterion_text":"- 9. Evidence of active UTI that in the investigator’s opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment"}

Primary endpoints

• {"endpoint_text":"- CRR, defined as the proportion of patients who achieved CR at the 3-month Visit (3 months after the first instillation of UGN-103) as determined by cystoscopy, for cause biopsy, and urine cytology.","definition_or_measurement_approach":"Proportion of patients who achieved complete response (CR) at the 3-month Visit (3 months after first instillation), as determined by cystoscopy, for-cause biopsy, and urine cytology."}

Secondary endpoints

• {"endpoint_text":"- 1. DOR in patients who achieved CR at the 3-m Visit, defined as the time from the date of evidence of CR at the 3-m Visit to the earliest date of recurrence or progression as determined using the date of cystoscopy, for cause biopsy, or cytology, or death due to any cause, whichever occurred first.","definition_or_measurement_approach":"Time from documented CR at 3-month Visit to earliest date of recurrence or progression determined by cystoscopy, for-cause biopsy, cytology, or death from any cause."}
• {"endpoint_text":"- 2. Safety and tolerability will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and l laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs)","definition_or_measurement_approach":"Assessment via adverse event reporting (AEs, SAEs, AESIs) and routine clinical/laboratory tests (hematology, chemistry, urinalysis), physical exam and vital signs."}
• {"endpoint_text":"- 3. Concentration data and PK parameters (Cmax, tmax, and AUC","definition_or_measurement_approach":"Pharmacokinetic measurement of mitomycin plasma concentration and PK parameters including Cmax, tmax and AUC in a subgroup."}
• {"endpoint_text":"- Exploratory 1. Changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires","definition_or_measurement_approach":"Patient-reported outcomes measured by QLQ-C30 and TSQM change from baseline."}
• {"endpoint_text":"- Exploratory 2. DNA, RNA and/or protein biomarkers in tumor tissue","definition_or_measurement_approach":"Analysis of tumor tissue biomarkers at DNA, RNA and/or protein level."}
• {"endpoint_text":"- Exploratory 3. Number (%) of response outcomes evaluated at the first disease assessment visit after SoC","definition_or_measurement_approach":"Proportion/count of response outcomes at first disease assessment visit after standard-of-care (SoC) treatment."}

Bulgaria

Earliest CTIS Part Ii Submission Date

09-08-2024

Latest Decision Or Authorization Date

16-08-2024

Processing Time Days

7

Number Of Sites

9

Number Of Participants

16

Estonia

Earliest CTIS Part Ii Submission Date

16-05-2024

Latest Decision Or Authorization Date

19-08-2024

Processing Time Days

95

Number Of Sites

4

Number Of Participants

7

Latvia

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

15-08-2024

Processing Time Days

30

Number Of Sites

3

Number Of Participants

8

Romania

Earliest CTIS Part Ii Submission Date

16-05-2024

Latest Decision Or Authorization Date

19-08-2024

Processing Time Days

95

Number Of Sites

6

Number Of Participants

13

Spain

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

14-08-2024

Processing Time Days

2

Number Of Sites

5

Number Of Participants

13

Primary sponsor

Full Name

Urogen Pharma Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Israel

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"ClinChoice","duties_or_roles":"sponsorDuties codes: [6]","organisation_type":"Industry"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"sponsorDuties: ePro - Patient Questionnaires","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Myonex LLC","duties_or_roles":"sponsorDuties: Ancillary Supplies (code 15)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"sponsorDuties: IP Supplies (value: IP Supplies)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"sponsorDuties codes: [1,11,12,15(value: Insurance procurement),2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Viedoc","duties_or_roles":"sponsorDuties: ePro - Patient Questionnaires","organisation_type":"Industry"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}