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 study aims to demonstrate that home instillation of UGN-102 is a feasible alternative to instillation in a clinical setting, which might mitigate patient challenges (logistical, expense, and comfort) when receiving treatment for low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
Detailed description
The primary objective of this study was to evaluate the feasibility of home instillation of UGN-102 as an alternative to instillation in a clinical setting. Feasibility was assessed by evaluation of safety and tolerability, rate of discontinuation from at home study treatment, and feedback from patients, home health professionals (HHPs), and investigators via standardized questionnaires. The secondary objective of this study was to evaluate the efficacy of UGN-102 for treatment of LG-IR-NMIBC following home instillation. Efficacy was assessed at the 3-month Visit (3 months after the first instillation of UGN-102) by the complete response rate (CRR), defined as the proportion of patients who achieved a complete response (CR) as determined by cystoscopy, for cause biopsy, and urine cytology. Patients who provided informed consent underwent a Screening Visit to determine eligibility. Screening procedures were to provide evidence of LG-NMIBC and to rule out evidence of high-grade (HG) disease. Eligible patients were to receive 6 once-weekly intravesical instillations of UGN-102. The first instillation was performed at the investigative site and subsequent instillations were performed at the patient's home by a trained HHP. The HHP was to call the patient 1 to 2 days after each home instillation of UGN-102 to monitor for safety. At each home instillation visit, the patient and HHP were to complete a feasibility questionnaire. In addition, the patient and investigator were to complete a feasibility questionnaire at the 3-month Visit (end of study) or Early Termination Visit. Patients were to return to the clinic for the 3-month Visit for determination of response to treatment. Response was determined based on visual evaluation by cystoscopy (white light) (appearance, number, and size of any remaining lesions), interpretation of urine cytology, and for cause biopsy and histopathology of any remaining lesions. Any lesions or suspect tissue were to be biopsied to evaluate for persistence of disease. Safety was evaluated based on review of adverse events (AEs), laboratory assessments, vital signs, and physical examination. A patient was considered to have completed the study if the patient completed the 3-month Visit. Following the 3-month Visit, all patients exited the study and continued with standard of care according to their treating physician.
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 newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. 3. Has IR disease, defined as having 1 or 2 of the following: * Presence of multiple tumors. * Solitary tumor \> 3 cm. * Recurrence (≥ 1 occurrence of LG-NMIBC within 1 year of the current diagnosis at the initial Screening Visit). 4. Negative voiding cytology for HG disease within 6 weeks before Screening. 5. Has adequate organ and bone marrow function as determined by routine laboratory tests: * Leukocytes ≥ 3,000/μL (≥ 3 × 10\^9/L). * Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 10\^9/L). * Platelets ≥ 100,000/μL (≥ 100 × 10\^9/L). * Hemoglobin ≥ 9.0 g/dL. * Total bilirubin ≤ 1.5 × ULN. * AST and ALT ≤ 2.5 × ULN. * Alkaline phosphatase ≤ 2.5 × ULN. * Estimated glomerular filtration rate ≥ 30 mL/min. 6. Has no evidence of active urinary tract infection at the Screening and baseline visits. 7. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) by an appropriately trained home health professional. 8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. 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 first instillation through 6 months post treatment. Acceptable methods of birth control that are considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly include implants, injections, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only hormonal), condoms with spermicide, sexual abstinence, or vasectomized partner. 9. Has an anticipated life expectancy of at least the duration of the trial.
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 T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent upper tract UC. 7. 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. 8. 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. 9. Has participated in a study with an investigational agent or device within 30 days of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs of Special Interest. | Up to 3 months | The number of patients with each type of event will be summarized. TEAEs were defined as adverse events (AEs) that occurred 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) Laboratory Values | Up to 3 months | PCS laboratory criteria were defined for the following parameters: Hematology * Hemoglobin \< 0.8 × lower limit of normal and \> 20% decrease from baseline or \> 1.3 × upper limit of normal (ULN) and \> 30% increase from baseline. * Leukocytes ≤ 2.8 or ≥ 16 × 10\^3/µL. * Lymphocytes \< 0.5 or \> 20 × 10\^3/µL. * Neutrophils \< 1.0 × 10\^3/µL. * Platelets \< 75 or ≥ 700 × 10\^3/µL. Chemistry * Creatinine \> 2.2 mg/dL. * Sodium ≤ 130 or \> 150 mEq/L. * Potassium \< 3.0 or \> 5.5 mEq/L. * Total bilirubin \> 1.5 × ULN. * Alanine aminotransferase (ALT) \> 3 × ULN. * Aspartate aminotransferase (AST) \> 3 × ULN. * Gamma glutamyl transferase \> 2.5 × ULN. |
| Composite Score for the Post-instillation Patient Questionnaire | Up to 5 weeks | Patients were asked to rate their experience receiving UGN-102 at home after each instillation was completed. A total of 5 domains (8 questions) were assessed: * Comfort (3 questions, possible range from 3 least favorable to 12 most favorable). * Safety/concerns (1 question, possible range from 1 least favorable to 4 most favorable). * Communication (2 questions, possible range from 2 least favorable to 8 most favorable). * Preference compared to office instillation (1 question, possible range from 1 least favorable to 4 most favorable). * Overall experience/satisfaction (1 question, possible range from 1 least favorable to 4 most favorable). A composite score (sum of all 8 question scores) was also calculated (possible range from 8 least favorable to 32 most favorable). |
| Responses to the Post-instillation Home Health Professional Questionnaire | Up to 5 weeks | Home health professionals (HHPs) were asked to share their experience administering UGN-102 at the patient's home after each instillation was completed. A total of 4 domains (4 questions) were assessed: * Comfort - Were you comfortable performing the instillation at this patient's home, yes (most favorable) or no (least favorable)? * Difficulty - Was it difficult to perform the instillation at this patient's home, yes (least favorable) or no (most favorable)? * Safety/concerns - Did you have any concerns performing the instillation in the home setting, yes (least favorable) or no (most favorable)? * Adequate support - Did you have sufficient support performing the instillation in the home setting, yes (most favorable) or no (least favorable)? The number of patients whose HHP had a most favorable response to all 4 questions is summarized for each home instillation. |
| Responses to End of Study Patient and Investigator Questionnaires | 3 months | Patient recommendations regarding home instillation of UGN-102 were collected at the 3-month Visit or Early Termination Visit. Two questions were asked: * Will you recommend home instillations of UGN-102 for other patients with NMIBC, yes (most favorable) or no (least favorable)? * Will you recommend home instillations of UGN-102 instead of having transurethral resection of bladder tumor (TURBT) for other patients with NMIBC, yes (most favorable) or no (least favorable)? The number of patients who had a most favorable response is summarized by question. In addition, investigators were asked if the experience of having their patient receive instillations at home was less difficult (most favorable), more difficult (least favorable), or not different than having them receive instillations in the office. All responses are summarized. |
Secondary
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UGN-102 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin). | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | UGN-102 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year No | 2 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year Yes | 6 Participants |
| Previous Low-grade (LG) Non-muscle Invasive Bladder Cancer (NMIBC) Episode(s) No | 0 Participants |
| Previous Low-grade (LG) Non-muscle Invasive Bladder Cancer (NMIBC) Episode(s) Yes | 8 Participants |
| Prior Transurethral Resection of Bladder Tumor (TURBT) No | 0 Participants |
| Prior Transurethral Resection of Bladder Tumor (TURBT) Yes | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
| Smoking History No | 3 Participants |
| Smoking History Yes | 5 Participants |
| Tumor Burden ≤ 3 cm | 4 Participants |
| Tumor Burden > 3 cm | 4 Participants |
| Tumor Count Multiple | 5 Participants |
| Tumor Count Single | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Composite Score for the Post-instillation Patient Questionnaire
Patients were asked to rate their experience receiving UGN-102 at home after each instillation was completed. A total of 5 domains (8 questions) were assessed: * Comfort (3 questions, possible range from 3 least favorable to 12 most favorable). * Safety/concerns (1 question, possible range from 1 least favorable to 4 most favorable). * Communication (2 questions, possible range from 2 least favorable to 8 most favorable). * Preference compared to office instillation (1 question, possible range from 1 least favorable to 4 most favorable). * Overall experience/satisfaction (1 question, possible range from 1 least favorable to 4 most favorable). A composite score (sum of all 8 question scores) was also calculated (possible range from 8 least favorable to 32 most favorable).
Time frame: Up to 5 weeks
Population: All patients who received any dose of UGN-102.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UGN-102 | Composite Score for the Post-instillation Patient Questionnaire | Post 2nd instillation | 32 score on a scale |
| UGN-102 | Composite Score for the Post-instillation Patient Questionnaire | Post 3rd instillation | 32 score on a scale |
| UGN-102 | Composite Score for the Post-instillation Patient Questionnaire | Post 6th instillation | 32 score on a scale |
| UGN-102 | Composite Score for the Post-instillation Patient Questionnaire | Post 4th instillation | 32 score on a scale |
| UGN-102 | Composite Score for the Post-instillation Patient Questionnaire | Post 5th instillation | 32 score on a scale |
Primary
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values
PCS laboratory criteria were defined for the following parameters: Hematology * Hemoglobin \< 0.8 × lower limit of normal and \> 20% decrease from baseline or \> 1.3 × upper limit of normal (ULN) and \> 30% increase from baseline. * Leukocytes ≤ 2.8 or ≥ 16 × 10\^3/µL. * Lymphocytes \< 0.5 or \> 20 × 10\^3/µL. * Neutrophils \< 1.0 × 10\^3/µL. * Platelets \< 75 or ≥ 700 × 10\^3/µL. Chemistry * Creatinine \> 2.2 mg/dL. * Sodium ≤ 130 or \> 150 mEq/L. * Potassium \< 3.0 or \> 5.5 mEq/L. * Total bilirubin \> 1.5 × ULN. * Alanine aminotransferase (ALT) \> 3 × ULN. * Aspartate aminotransferase (AST) \> 3 × ULN. * Gamma glutamyl transferase \> 2.5 × ULN.
Time frame: Up to 3 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 Potentially Clinically Significant (PCS) Laboratory Values | Hematology | 0 Participants |
| UGN-102 | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values | Chemistry | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs of Special Interest.
The number of patients with each type of event will be summarized. TEAEs were defined as adverse events (AEs) that occurred 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 3 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, TEAEs Leading to Discontinuation, and TEAEs of Special Interest. | Any serious TEAEs | 3 Participants |
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs of Special Interest. | Any TEAEs | 8 Participants |
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs of Special Interest. | Any TEAEs leading to discontinuation | 2 Participants |
| UGN-102 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation, and TEAEs of Special Interest. | Any TEAEs of special interest | 7 Participants |
Primary
Responses to End of Study Patient and Investigator Questionnaires
Patient recommendations regarding home instillation of UGN-102 were collected at the 3-month Visit or Early Termination Visit. Two questions were asked: * Will you recommend home instillations of UGN-102 for other patients with NMIBC, yes (most favorable) or no (least favorable)? * Will you recommend home instillations of UGN-102 instead of having transurethral resection of bladder tumor (TURBT) for other patients with NMIBC, yes (most favorable) or no (least favorable)? The number of patients who had a most favorable response is summarized by question. In addition, investigators were asked if the experience of having their patient receive instillations at home was less difficult (most favorable), more difficult (least favorable), or not different than having them receive instillations in the office. All responses are summarized.
Time frame: 3 months
Population: All patients who received any dose of UGN-102 and who completed the end of study questionnaire.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 | Responses to End of Study Patient and Investigator Questionnaires | Recommend home instillations of UGN-102 for other NMIBC patients = yes | 5 Participants |
| UGN-102 | Responses to End of Study Patient and Investigator Questionnaires | Recommend home instillations of UGN-102 instead of having TURBT = yes | 5 Participants |
| UGN-102 | Responses to End of Study Patient and Investigator Questionnaires | Having patient receive instillations at home is less difficult than in office | 0 Participants |
| UGN-102 | Responses to End of Study Patient and Investigator Questionnaires | Having patient receive instillations at home is more difficult than in office | 1 Participants |
| UGN-102 | Responses to End of Study Patient and Investigator Questionnaires | Having patient receive instillations at home is not different than in office | 5 Participants |
Primary
Responses to the Post-instillation Home Health Professional Questionnaire
Home health professionals (HHPs) were asked to share their experience administering UGN-102 at the patient's home after each instillation was completed. A total of 4 domains (4 questions) were assessed: * Comfort - Were you comfortable performing the instillation at this patient's home, yes (most favorable) or no (least favorable)? * Difficulty - Was it difficult to perform the instillation at this patient's home, yes (least favorable) or no (most favorable)? * Safety/concerns - Did you have any concerns performing the instillation in the home setting, yes (least favorable) or no (most favorable)? * Adequate support - Did you have sufficient support performing the instillation in the home setting, yes (most favorable) or no (least favorable)? The number of patients whose HHP had a most favorable response to all 4 questions is summarized for each home instillation.
Time frame: Up to 5 weeks
Population: All patients who received any dose of UGN-102.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 | Responses to the Post-instillation Home Health Professional Questionnaire | Post 2nd instillation | 8 Participants |
| UGN-102 | Responses to the Post-instillation Home Health Professional Questionnaire | Post 3rd instillation | 7 Participants |
| UGN-102 | Responses to the Post-instillation Home Health Professional Questionnaire | Post 4th instillation | 7 Participants |
| UGN-102 | Responses to the Post-instillation Home Health Professional Questionnaire | Post 5th instillation | 7 Participants |
| UGN-102 | Responses to the Post-instillation Home Health Professional Questionnaire | Post 6th instillation | 5 Participants |
Secondary
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) | 75.0 percentage of participants |