Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder
Conditions
Keywords
Non-muscle invasive bladder cancer, Low grade non-muscle invasive bladder cancer, Intermediate risk non-muscle invasive bladder cancer, NMIBC, UGN-102, Mitomycin
Brief summary
This Phase 3, multinational, single-arm study was designed to evaluate the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
Detailed description
Eligible patients received 6 once-weekly intravesical instillations of UGN-102. All patients returned to the clinic approximately 3 months after the first instillation for determination of response to treatment. Assessment of response was based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions by central pathology lab (if applicable), and interpretation of urine cytology by central pathology lab. Patients who had a complete response (CR) at the 3-month Visit, defined as having no detectable disease in the bladder, entered the Follow-up Period of the study. Patients who had a non-complete response (NCR) due to residual LG disease underwent investigator-designated standard of care (SOC) treatment of remaining lesions and then entered the Follow-up Period of the study. During the Follow-up Period, patients return to the clinic every 3 months for up to 24 months (ie, 27 months after the first instillation) for evaluation of response. Patients who remain disease free at the 27-month Visit will continue to be followed every 6 months for up to 36 months (ie, 63 months after the first instillation) or until disease recurrence, disease progression, death, or the study is closed by the sponsor, whichever occurs first. Patients who had a disease recurrence during the Follow-up Period or a disease progression at any time underwent investigator-designated SOC treatment and had a separate End of Study (EOS) Visit performed. The timing of the EOS Visit was approximately 3 months after SOC treatment of disease recurrence or progression. Study conduct is ongoing and data are summarized through a cutoff date of 04 Apr 2024. As of the data cutoff date, ongoing patients were followed through at least Study Month 15, with the earliest enrolled patients followed through Study Month 21.
Interventions
DRUGUGN-102
UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.
Sponsors
UroGen Pharma Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and the protocol. 2. Patient who has LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. 3. History of LG-NMIBC requiring treatment with transurethral resection of bladder tumors (TURBT). Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened. 4. Has intermediate-risk disease, defined as having 1 or 2 of the following: * Presence of multiple tumors; * Solitary tumor \> 3 cm; * Early or frequent recurrence (≥ 1 occurrence of LG-NMIBC within 1 year of the current diagnosis at the initial Screening Visit). 5. Negative voiding cytology for high-grade (HG) disease within 8 weeks before Screening. 6. Has adequate organ and bone marrow function as determined by routine laboratory tests as below: * Leukocytes ≥ 3,000 per μL; * Absolute neutrophil count ≥ 1,500 per μL; * Platelets ≥ 100,000 per μL; * Hemoglobin ≥ 9.0 g/dL; * Total bilirubin ≤ 1.5 x upper limit of normal (ULN); * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN; * Alkaline phosphatase ≤ 2.5 × ULN; * Estimated glomerular filtration rate ≥ 30 mL/min. 7. Has an anticipated life expectancy of at least the duration of the trial. 8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post-treatment.
Exclusion criteria
1. Received Bacillus Calmette-Guérin treatment for urothelial carcinoma (UC) within previous 1 year. 2. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years. 3. Known allergy or sensitivity to mitomycin that in the Investigator's opinion cannot be readily managed. 4. Clinically significant urethral stricture that would preclude passage of a urethral catheter. 5. History of: * Neurogenic bladder; * Active urinary retention; * Any other condition that would prohibit normal voiding. 6. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC. 7. Current tumor grading of T1. 8. Concurrent upper tract UC. 9. Evidence of active urinary tract infection that in the Investigator's opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment. 10. Is pregnant or breastfeeding. 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. 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. 13. Has participated in a study with an investigational agent or device within 30 days of enrollment. 14. Has previously participated in a study in which they received UGN-102. 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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | 3 months | CRR is defined as the percentage of patients who achieved a complete response (CR) at the 3-month Visit. A patient was considered a CR if there was no detectable disease in the bladder based on visual observation (white light cystoscopy), biopsy of remaining lesions (if applicable), and voiding urine cytology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) in Patients Who Achieved CR at the 3-month Visit | Up to 60 months | DOR is defined as the time from the first documented CR 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. |
| Durable Complete Response (DCR) Rate in Patients Who Achieved CR at the 3-month Visit | Up to 60 months | DCR rate at scheduled disease assessment time points is defined as the percentage of patients who had a CR at the 3-month Visit and maintained CR up to that particular follow-up visit. |
| Disease-free Survival (DFS) in Patients Who Achieved CR at the 3-month Visit | Up to 63 months | DFS is defined as the time from the first instillation 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Up to 21 months | The number of patients with each type of event is summarized. TEAEs were defined as adverse events (AEs) that started on or after the day of the first instillation of UGN-102 or pre-treatment AEs that worsened during the study. |
| Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | 6 months | The number of patients with each type of event is summarized. |
| Number of Participants With Post-baseline PCS Chemistry Values | 6 months | The number of patients with each type of event is summarized. |
Countries
Austria, Bulgaria, Estonia, Georgia, Latvia, Lithuania, Poland, Serbia, Spain, United States
Contacts
PRINCIPAL_INVESTIGATORSandip Prasad, MD
Atlantic Health System
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UGN-102 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin). | 240 |
| Total | 240 |
Baseline characteristics
| Characteristic | UGN-102 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 162 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants |
| Age, Continuous | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Longest Tumor Diameter ≤ 3 cm | 216 Participants |
| Longest Tumor Diameter > 3 cm | 19 Participants |
| Longest Tumor Diameter Missing | 5 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year No | 116 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year Yes | 124 Participants |
| Previous Low-grade Non-muscle Invasive Bladder Cancer (LG-NMIBC) Episode(s) No | 11 Participants |
| Previous Low-grade Non-muscle Invasive Bladder Cancer (LG-NMIBC) Episode(s) Yes | 229 Participants |
| Prior Transurethral Resection of Bladder Tumor (TURBT) to Treat LG-NMIBC No | 12 Participants |
| Prior Transurethral Resection of Bladder Tumor (TURBT) to Treat LG-NMIBC Yes | 228 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 234 Participants |
| Region of Enrollment Austria | 2 Participants |
| Region of Enrollment Bulgaria | 85 Participants |
| Region of Enrollment Estonia | 14 Participants |
| Region of Enrollment Georgia | 20 Participants |
| Region of Enrollment Latvia | 38 Participants |
| Region of Enrollment Lithuania | 7 Participants |
| Region of Enrollment Poland | 7 Participants |
| Region of Enrollment Serbia | 18 Participants |
| Region of Enrollment Spain | 8 Participants |
| Region of Enrollment United States | 41 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 147 Participants |
| Smoking History Non-smoker | 112 Participants |
| Smoking History Smoker | 128 Participants |
| Tumor Burden ≤ 3 cm | 180 Participants |
| Tumor Burden > 3 cm | 41 Participants |
| Tumor Burden Missing | 19 Participants |
| Tumor Count Missing | 1 Participants |
| Tumor Count Multiple | 198 Participants |
| Tumor Count Single | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 240 |
| other Total, other adverse events | 129 / 240 |
| serious Total, serious adverse events | 29 / 240 |
Outcome results
Primary
Complete Response Rate (CRR)
CRR is defined as the percentage of patients who achieved a complete response (CR) at the 3-month Visit. A patient was considered a CR if there was no detectable disease in the bladder based on visual observation (white light cystoscopy), biopsy of remaining lesions (if applicable), and voiding urine cytology.
Time frame: 3 months
Population: All patients who received any dose of UGN-102.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UGN-102 | Complete Response Rate (CRR) | 76.7 percentage of participants |
Secondary
Disease-free Survival (DFS) in Patients Who Achieved CR at the 3-month Visit
DFS is defined as the time from the first instillation 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.
Time frame: Up to 63 months
Secondary
Durable Complete Response (DCR) Rate in Patients Who Achieved CR at the 3-month Visit
DCR rate at scheduled disease assessment time points is defined as the percentage of patients who had a CR at the 3-month Visit and maintained CR up to that particular follow-up visit.
Time frame: Up to 60 months
Secondary
Duration of Response (DOR) in Patients Who Achieved CR at the 3-month Visit
DOR is defined as the time from the first documented CR 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.
Time frame: Up to 60 months
Secondary
Number of Participants With Post-baseline PCS Chemistry Values
The number of patients with each type of event is summarized.
Time frame: 6 months
Population: All patients who received any dose of UGN-102 and who had a post-baseline laboratory value.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Alanine aminotransferase > 3 × ULN | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Aspartate aminotransferase > 3 × ULN | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Bilirubin > 1.5 × ULN | 6 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Creatinine > 194 μmol/L | 8 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Gamma glutamyl transferase > 2.5 × ULN | 11 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Potassium < 3.0 mmol/L | 0 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Potassium > 5.5 mmol/L | 20 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Sodium ≤ 130 mmol/L | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline PCS Chemistry Values | Sodium > 150 mmol/L | 0 Participants |
Secondary
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values
The number of patients with each type of event is summarized.
Time frame: 6 months
Population: All patients who received any dose of UGN-102 and who had a post-baseline laboratory value, except for hemoglobin, which required non-missing laboratory values at baseline and post-baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Hemoglobin < 0.8 × lower limit of normal and > 20% decrease from baseline | 8 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Hemoglobin > 1.3 × upper limit of normal (ULN) and > 30% increase from baseline | 0 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Lymphocytes < 0.5 × 10^9/L | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Lymphocytes > 20 × 10^9/L | 0 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Neutrophils < 1.0 × 10^9/L | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Platelets < 75 × 10^9/L | 1 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Platelets ≥ 700 × 10^9/L | 0 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≤ 2.8 × 10^9/L | 2 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≥ 16.0 × 10^9/L | 5 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest
The number of patients with each type of event is summarized. TEAEs were defined as adverse events (AEs) that started on or after the day of the first instillation of UGN-102 or pre-treatment AEs that worsened during the study.
Time frame: Up to 21 months
Population: All patients who received any dose of UGN-102.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs | 137 Participants |
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any serious TEAEs | 29 Participants |
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs of special interest | 100 Participants |