Olympus: The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study
Study Details
Study Description
Brief Summary
The study is investigating the ability of UroGen's UGN-101 to treat urothelial carcinoma tumors from the upper urinary tract.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Trial TC-UT-03 is a prospective, open label, single-arm trial, designed to assess the efficacy, safety, and tolerability of treatment with UGN-101 instilled in the upper urinary system of patients with non-invasive low-grade (LG), Upper Tract Urothelial Carcinoma (UTUC).
Upon signing of informed consent, the patients will undergo a screening visit for eligibility evaluation. Eligible patients will be treated with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.
Five (5) weeks (± 1 w) following the last instillation, the Primary Disease Evaluation (PDE) Visit, during which safety and efficacy will be assessed, will take place. During this visit, the ablative effect of the UGN-101 will be assessed visually, by upper tract washed urine cytology, and if there are remaining tumors, by biopsy or brush biopsy if technically feasible.
Patient demonstrating CR at PDE will undergo monthly maintenance instillations of UGN-101 up to 11 months post PDE. Safety follow-up for these patients will be done until one month post last instillation or at the end of the follow-up period in FU visit 12, which is the earlier.
For patients who did not demonstrate Complete Response, to the extent that it is possible, all remaining tumors lesions will be biopsied. The patients shall undergo any additional surgical or other treatment the Principal Investigator (PI) decides deem necessary to remove remaining tumor.
An independent Data Monitoring Committee (DMC) was assigned to this trial. Accumulating safety, tolerability and efficacy data will be monitored periodically by the DMC according to a pre-specified process and frequency detailed in the DMC charter.
Study Design
Arms and Interventions
| 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, maximum dose is 15ml. 6 once weekly intravesical instillations for the ablation treatment. |
Drug: UGN-101 instillations
Treatment with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit). [An average of 11 weeks]
The primary efficacy endpoint was the number of patients attaining complete response (CR) at the end of the treatment period (Primary Disease Evaluation (PDE) visit). The CR was defined dichotomously as "Success" if CR was confirmed at PDE visit (or relevant follow-up), and "Failure" otherwise.
Secondary Outcome Measures
- The Key Secondary Efficacy Endpoint Was Long-term Durability of Complete Response (CR): Number of Patients Who Maintained CR at 12 Month Post PDE Visit. This Endpoint Was Defined Only for Those Patients Who Achieved CR at the PDE Visit. [12 months]
Continuously: Duration of CR or time-to-recurrence since the Primary Disease Evaluation (PDE) Visit (i.e., time in days from the visit at which CR was determined until recurrence or censoring). This endpoint served as the main long-term durability endpoint. Dichotomously: "Success" if CR was still present at the 12 month post-PDE Visit (at Follow-Up Visit 4), and "Failure" otherwise. This endpoint served as a supportive long-term durability endpoint.
- Durability of Complete Response (CR) for Each Follow-up Time Point. [3, 6, 9 and 12 months]
Durability of CR defined dichotomously as "Success" if CR was achieved at Primary Disease Evaluation (PDE) visit and remained at follow-up Visit 1, Visit 2 and Visit 3 (3, 6, 9 and 12 months post PDE visit), and "Failure" otherwise.
- Clinical Benefit for Patients With Partial Response (PR) at the Primary Disease Evaluation (PDE) Visit. Clinical Benefit Endpoint Was Analyzed Using the Intent-to-Treat (ITT) Analysis Set, Including Patients Who Achieved Partial Response at PDE Visit. [An average of 11 weeks]
Clinical benefit for patients with partial response (PR) at the PDE visit. Clinical benefit endpoint was analyzed using the Intent-to-Treat (ITT) Analysis Set, including patients who achieved partial response at PDE Visit.Partial response at PDE visit will be defined dichotomously, similarly to the primary efficacy endpoint. For subjects with partial response at PDE visit, originally planned and actual treatments will be compared.
- Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. [Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation of UGN-101]
Cmax: maximum plasma concentration Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL). The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.
- Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. [Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101]
Tmax: time to maximum plasma concentration Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL), and the Tmax was 1.79 hours (range: 0.50 to 5.17 hours) after instillation. The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.
- Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. [Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101]
Half-life (t½): terminal half-life The mean apparent t½ following instillation of mitomycin into the upper urinary tract (UUT) was 1.27 hours (76 minutes), which was longer than the true t½ of mitomycin following a 30 mg bolus injection (mean t½ value of approximately 17 minutes). The apparent t½ demonstrates that UGN-101 dissolved gradually, resulting in prolonged exposure of mitomycin following local instillation into the UUT.
Other Outcome Measures
- Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs). [Through study completion, an average of 15 months]
Treatment-emergent AEs were most frequently reported from the Renal and urinary disorders system organ class (SOC), 59 (83.1%) patients, as expected, given the underlying indication of low grade (LG) Upper tract urothelial carcinoma (UTUC) in the study population, chemotherapeutic drug in a gel matrix instilled in the upper urinary tract (UUT), and the study procedure of treatment instillation via a ureteral catheter. The toxicity within the upper urinary tract was considered consistent with the disease under study and the mode of administration of UGN-101. Most events in the Renal and urinary disorders SOC were mild to moderate in severity and resolved. No new risks were identified and the overall safety profile was consistent with the known safety profile of endoscopic administration of intravesical mitomycin and of mitomycin. Overall, based on the safety and efficacy results to date, the benefit-risk profile of UGN-101 is favorable for the treatment of LG-UTUC.
Eligibility Criteria
Criteria
Main Inclusion Criteria:
-
Patient is at least 18 years of age.
-
Naive or recurrent patients with low grade (LG), non-invasive Upper Tract Urothelial Carcinoma (UTUC) in the pyelocalyceal system.
-
Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15mm.
-
Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening.
-
Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm.
-
Wash urine cytology sampled from the pyelocalyceal system documenting the absence of High Grade (HG) urothelial cancer, diagnosed not more than 2 months prior to the screening.
-
Patient with bilateral LG UTUC may be enrolled if at least one side meets the inclusion criteria for the trial and if the other kidney does not require further treatments (The other kidney can be treated prior to the beginning of the study).
Main Exclusion Criteria:
-
Patient received Bacille de Calmette et Guérin (BCG) treatment for Urothelial carcinoma (UC) during the 6 months prior to Visit 1.
-
The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening)
-
Carcinoma in situ (CIS) in the past in the urinary tract.
-
Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years.
-
Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years.
-
Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Hospital | Phoenix | Arizona | United States | 85054 |
| 2 | Loma Linda Cancer Center | Loma Linda | California | United States | 92354 |
| 3 | University of California | Los Angeles | California | United States | 90095 |
| 4 | Providence Medical Institute | Santa Monica | California | United States | 90404 |
| 5 | Mayo Clinic Florida | Jacksonville | Florida | United States | 32224 |
| 6 | Loyola University Medical Center, Department of Urology | Maywood | Illinois | United States | 60153 |
| 7 | Indiana University School of Medicine | Indianapolis | Indiana | United States | 46202 |
| 8 | John Hopkins University | Baltimore | Maryland | United States | 21218 |
| 9 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
| 10 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 11 | Mayo Clinic health system | Rochester | Minnesota | United States | 55905 |
| 12 | Urology Center Las Vegas | Las Vegas | Nevada | United States | 89144 |
| 13 | Montefiore Medical Center (Albert Einstein) | Bronx | New York | United States | 10467 |
| 14 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 15 | Weill Cornell Medical Center | New York | New York | United States | 10065 |
| 16 | University of north carolina - chapel hill | Chapel Hill | North Carolina | United States | 27514 |
| 17 | The Ohio State University Wexner Medical Center | Columbus | Ohio | United States | 43210 |
| 18 | Penn State College of Medicine | Hershey | Pennsylvania | United States | 17033 |
| 19 | Thomas Jefferson University Hospitals | Philadelphia | Pennsylvania | United States | 19107 |
| 20 | MD Anderson | Houston | Texas | United States | 77006 |
| 21 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 22 | Seattle Cancer Care Alliance (University of Washington) | Seattle | Washington | United States | 98109--1023 |
| 23 | Hasharon Hospital (Rabin Medical Center) | Petah Tikva | Israel | 49372 | |
| 24 | Sheba Medical Center | Ramat Gan | Israel | 52621 |
Sponsors and Collaborators
- UroGen Pharma Ltd.
Investigators
- Study Chair: Seth Lerner, M.D., Baylor College of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.- TC-UT-03-P
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT). Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen. |
| Period Title: Overall Study | |
| STARTED | 71 |
| COMPLETED | 62 |
| NOT COMPLETED | 9 |
Baseline Characteristics
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT. Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen. |
| Overall Participants | 71 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
18
25.4%
|
| >=65 years |
53
74.6%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
71
|
| Sex: Female, Male (Count of Participants) | |
| Female |
23
32.4%
|
| Male |
48
67.6%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
4
5.6%
|
| White |
62
87.3%
|
| More than one race |
3
4.2%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
57
80.3%
|
| Israel |
14
19.7%
|
Outcome Measures
| Title | The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit). |
|---|---|
| Description | The primary efficacy endpoint was the number of patients attaining complete response (CR) at the end of the treatment period (Primary Disease Evaluation (PDE) visit). The CR was defined dichotomously as "Success" if CR was confirmed at PDE visit (or relevant follow-up), and "Failure" otherwise. |
| Time Frame | An average of 11 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT. Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen. |
| Measure Participants | 71 |
| Count of Participants [Participants] |
42
59.2%
|
| Title | The Key Secondary Efficacy Endpoint Was Long-term Durability of Complete Response (CR): Number of Patients Who Maintained CR at 12 Month Post PDE Visit. This Endpoint Was Defined Only for Those Patients Who Achieved CR at the PDE Visit. |
|---|---|
| Description | Continuously: Duration of CR or time-to-recurrence since the Primary Disease Evaluation (PDE) Visit (i.e., time in days from the visit at which CR was determined until recurrence or censoring). This endpoint served as the main long-term durability endpoint. Dichotomously: "Success" if CR was still present at the 12 month post-PDE Visit (at Follow-Up Visit 4), and "Failure" otherwise. This endpoint served as a supportive long-term durability endpoint. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | Population was analyzed at 12 months post Primary Disease Evaluation (PDE) visit. 8 out of 41 patients had disease recurrence. The Kaplan-Meier estimate of 12 month duration of complete response (CR) rate was 82%. This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT). Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen. |
| Measure Participants | 41 |
| Count of Participants [Participants] |
23
32.4%
|
| Title | Durability of Complete Response (CR) for Each Follow-up Time Point. |
|---|---|
| Description | Durability of CR defined dichotomously as "Success" if CR was achieved at Primary Disease Evaluation (PDE) visit and remained at follow-up Visit 1, Visit 2 and Visit 3 (3, 6, 9 and 12 months post PDE visit), and "Failure" otherwise. |
| Time Frame | 3, 6, 9 and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | UGN-101 Patients Evaluated 3 Months Post PDE | UGN-101 Patients Evaluated at 6 Months Post PDE | UGN-101 Patients Evaluated at 9 Months Post PDE | UGN-101 Patients Evaluated at 12 Months Post PDE |
|---|---|---|---|---|
| Arm/Group Description | Patients reaching CR at PDE evaluated at 3 months post PDE | Patients reaching CR at PDE evaluated at 6 months post PDE | Patients reaching CR at PDE evaluated at 9 months post PDE | Patients reaching CR at PDE evaluated at 12 months post PDE |
| Measure Participants | 38 | 38 | 35 | 31 |
| Count of Participants [Participants] |
35
49.3%
|
33
NaN
|
28
NaN
|
23
NaN
|
| Title | Clinical Benefit for Patients With Partial Response (PR) at the Primary Disease Evaluation (PDE) Visit. Clinical Benefit Endpoint Was Analyzed Using the Intent-to-Treat (ITT) Analysis Set, Including Patients Who Achieved Partial Response at PDE Visit. |
|---|---|
| Description | Clinical benefit for patients with partial response (PR) at the PDE visit. Clinical benefit endpoint was analyzed using the Intent-to-Treat (ITT) Analysis Set, including patients who achieved partial response at PDE Visit.Partial response at PDE visit will be defined dichotomously, similarly to the primary efficacy endpoint. For subjects with partial response at PDE visit, originally planned and actual treatments will be compared. |
| Time Frame | An average of 11 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT. Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen. |
| Measure Participants | 71 |
| Count of Participants [Participants] |
8
11.3%
|
| Title | Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. |
|---|---|
| Description | Cmax: maximum plasma concentration Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL). The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin. |
| Time Frame | Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation of UGN-101 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Consisted of patients who signed consent for PK and had sufficient PK data for the determination of PK parameters. |
| Arm/Group Title | Pharmacokinetic Population |
|---|---|
| Arm/Group Description | The PK profiles of the first UGN-101 instillation in the blood were to be examined for the first 6 patients. |
| Measure Participants | 6 |
| Mean (Inter-Quartile Range) [ng/mL] |
6.24
|
| Title | Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs). |
|---|---|
| Description | Treatment-emergent AEs were most frequently reported from the Renal and urinary disorders system organ class (SOC), 59 (83.1%) patients, as expected, given the underlying indication of low grade (LG) Upper tract urothelial carcinoma (UTUC) in the study population, chemotherapeutic drug in a gel matrix instilled in the upper urinary tract (UUT), and the study procedure of treatment instillation via a ureteral catheter. The toxicity within the upper urinary tract was considered consistent with the disease under study and the mode of administration of UGN-101. Most events in the Renal and urinary disorders SOC were mild to moderate in severity and resolved. No new risks were identified and the overall safety profile was consistent with the known safety profile of endoscopic administration of intravesical mitomycin and of mitomycin. Overall, based on the safety and efficacy results to date, the benefit-risk profile of UGN-101 is favorable for the treatment of LG-UTUC. |
| Time Frame | Through study completion, an average of 15 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety: Consisted of all patients who enrolled in the study and received at least 1 instillation of UGN-101. |
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution |
|---|---|
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT). Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen. |
| Measure Participants | 71 |
| Treatment-emergent Adverse Events (TEAEs) |
67
94.4%
|
| TEAEs related to study drug |
52
73.2%
|
| TEAEs related to study procedure |
55
77.5%
|
| TEAEs related to study drug or preocedure |
61
85.9%
|
| Serious Adverse Events (SAE) |
28
39.4%
|
| SAEs related to study drug or procedure |
19
26.8%
|
| Title | Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. |
|---|---|
| Description | Tmax: time to maximum plasma concentration Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL), and the Tmax was 1.79 hours (range: 0.50 to 5.17 hours) after instillation. The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin. |
| Time Frame | Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Consisted of patients who signed consent for PK and had sufficient PK data for the determination of PK parameters. |
| Arm/Group Title | Pharmacokinetic Population |
|---|---|
| Arm/Group Description | The PK profiles of the first UGN-101 instillation in the blood were to be examined for the first 6 patients. |
| Measure Participants | 6 |
| Mean (Inter-Quartile Range) [Hours] |
1.79
|
| Title | Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients. |
|---|---|
| Description | Half-life (t½): terminal half-life The mean apparent t½ following instillation of mitomycin into the upper urinary tract (UUT) was 1.27 hours (76 minutes), which was longer than the true t½ of mitomycin following a 30 mg bolus injection (mean t½ value of approximately 17 minutes). The apparent t½ demonstrates that UGN-101 dissolved gradually, resulting in prolonged exposure of mitomycin following local instillation into the UUT. |
| Time Frame | Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Consisted of patients who signed consent for PK and had sufficient PK data for the determination of PK parameters. |
| Arm/Group Title | Pharmacokinetic Population |
|---|---|
| Arm/Group Description | The PK profiles of the first UGN-101 instillation in the blood were to be examined for the first 6 patients. |
| Measure Participants | 6 |
| Number [Hours] |
1.27
|
Adverse Events
| Time Frame | The study period for Adverse Events (AEs) collection was defined from the Informed Consent Form (ICF) signature and up to 30 days following the last administration of investigational product unless the AE was suspected to be related to the study treatment or was a Serious Adverse Event, in such case the AE should be reported regardless to the timelines of the reporting period. Through study completion, an average of 15 months. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | UGN-101 Mitomycin for Pyelocalyceal Solution | |
| Arm/Group Description | This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT). Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation. Eligible patients with confirmed Low Grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen. | |
All Cause Mortality |
||
| UGN-101 Mitomycin for Pyelocalyceal Solution | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/71 (7%) | |
Serious Adverse Events |
||
| UGN-101 Mitomycin for Pyelocalyceal Solution | ||
| Affected / at Risk (%) | # Events | |
| Total | 28/71 (39.4%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/71 (1.4%) | 1 |
| Iron deficiency anaemia | 1/71 (1.4%) | 1 |
| Pancytopenia | 1/71 (1.4%) | 1 |
| Thrombocytopenia | 1/71 (1.4%) | 1 |
| Cardiac disorders | ||
| Arrhythmia | 1/71 (1.4%) | 1 |
| Atrial fibrillation | 1/71 (1.4%) | 1 |
| Cardiac failure acute | 1/71 (1.4%) | 1 |
| Cardiac failure chronic | 1/71 (1.4%) | 1 |
| Cardiac failure congestive | 1/71 (1.4%) | 1 |
| Pericardial effusion | 1/71 (1.4%) | 1 |
| Pulmonary oedema | 1/71 (1.4%) | 1 |
| Supraventricular tachycardia | 1/71 (1.4%) | 1 |
| Gastrointestinal disorders | ||
| Vomiting | 2/71 (2.8%) | 2 |
| General disorders | ||
| Asthenia | 1/71 (1.4%) | 1 |
| Death | 1/71 (1.4%) | 1 |
| Pyrexia | 1/71 (1.4%) | 1 |
| Immune system disorders | ||
| Hypersensitivity | 1/71 (1.4%) | 1 |
| Infections and infestations | ||
| Gangrene | 1/71 (1.4%) | 1 |
| Pneumonia | 1/71 (1.4%) | 1 |
| Septic shock | 1/71 (1.4%) | 1 |
| Injury, poisoning and procedural complications | ||
| Burns third degree | 1/71 (1.4%) | 1 |
| Fall | 1/71 (1.4%) | 1 |
| Metabolism and nutrition disorders | ||
| Dehydration | 2/71 (2.8%) | 2 |
| Failure to thrive | 2/71 (2.8%) | 2 |
| Hyperglycaemia | 1/71 (1.4%) | 1 |
| Hyponatraemia | 1/71 (1.4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Ankle fracture | 1/71 (1.4%) | 1 |
| groin pain | 1/71 (1.4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Transitional cell cancer of renal pelvis and ureter metastatic | 1/71 (1.4%) | 1 |
| Nervous system disorders | ||
| Transient global amnesia | 1/71 (1.4%) | 1 |
| Renal and urinary disorders | ||
| Ureteric stenosis | 5/71 (7%) | 5 |
| Hyrdornephrosis | 4/71 (5.6%) | 4 |
| Flank Pain | 3/71 (4.2%) | 3 |
| Urosepsis | 3/71 (4.2%) | 3 |
| Heamaturia | 2/71 (2.8%) | 2 |
| Urinary tract infection | 2/71 (2.8%) | 2 |
| Acute kidney injury | 1/71 (1.4%) | 1 |
| Pelvi-ureteric obstruction | 1/71 (1.4%) | 1 |
| Pyelonephritis | 1/71 (1.4%) | 1 |
| Ureteric obstruction | 1/71 (1.4%) | 1 |
| Urinary tract obstruction | 1/71 (1.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Acute respiratory failure | 2/71 (2.8%) | 2 |
| Chronic obstructive pulmonary disease | 2/71 (2.8%) | 2 |
| Dyspnoea | 2/71 (2.8%) | 2 |
| Vascular disorders | ||
| Aortic dissection | 1/71 (1.4%) | 1 |
| Cerebrovascular accident | 1/71 (1.4%) | 1 |
| Hypotension | 1/71 (1.4%) | 1 |
| Subdural haematoma | 1/71 (1.4%) | 1 |
| Syncope | 1/71 (1.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| UGN-101 Mitomycin for Pyelocalyceal Solution | ||
| Affected / at Risk (%) | # Events | |
| Total | 67/71 (94.4%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 10/71 (14.1%) | 10 |
| Leukopenia | 4/71 (5.6%) | 4 |
| Thrombocytopenia | 4/71 (5.6%) | 4 |
| Gastrointestinal disorders | ||
| Nausea | 18/71 (25.4%) | 18 |
| Vomiting | 14/71 (19.7%) | 14 |
| Abdominal Pain | 14/71 (19.7%) | 14 |
| Diarrhoea | 6/71 (8.5%) | 6 |
| Abdominal pain lower | 6/71 (8.5%) | 6 |
| Constipation | 5/71 (7%) | 5 |
| General disorders | ||
| Fatigue | 11/71 (15.5%) | 11 |
| Pyrexia | 9/71 (12.7%) | 9 |
| Chills | 8/71 (11.3%) | 8 |
| Asthenia | 8/71 (11.3%) | 8 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 7/71 (9.9%) | 7 |
| Dehydration | 6/71 (8.5%) | 6 |
| Weight loss poor | 4/71 (5.6%) | 4 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 10/71 (14.1%) | 10 |
| Pain in extremity | 4/71 (5.6%) | 4 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Bladder transitional cell carcinoma | 6/71 (8.5%) | 6 |
| Nervous system disorders | ||
| Headache | 5/71 (7%) | 5 |
| Psychiatric disorders | ||
| Depression | 4/71 (5.6%) | 4 |
| Renal and urinary disorders | ||
| Ureteric stenosis | 31/71 (43.7%) | 31 |
| Urinary tract infection | 23/71 (32.4%) | 23 |
| Haematuria | 23/71 (32.4%) | 23 |
| Flank Pain | 22/71 (31%) | 22 |
| Dysuria | 16/71 (22.5%) | 16 |
| Renal impairment | 14/71 (19.7%) | 14 |
| Hydronephrosis | 13/71 (18.3%) | 13 |
| Pollakiuria | 10/71 (14.1%) | 10 |
| Acute kidney injury | 6/71 (8.5%) | 6 |
| urinary tract inflammation | 5/71 (7%) | 5 |
| Urinary tract obstruction | 5/71 (7%) | 5 |
| Pelvi-ureteric obstruction | 4/71 (5.6%) | 4 |
| Renal Failure | 4/71 (5.6%) | 4 |
| urine abnormality | 4/71 (5.6%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 5/71 (7%) | 5 |
| Cough | 4/71 (5.6%) | 4 |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 9/71 (12.7%) | 9 |
| Rash | 4/71 (5.6%) | 4 |
| Vascular disorders | ||
| Hypertension | 7/71 (9.9%) | 7 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Madlen Malinowski |
|---|---|
| Organization | UroGen Pharma Ltd. |
| Phone | 6467689533 |
| madlen.malinowski@urogen.com |
- TC-UT-03-P