A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (OPTIMA II)
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| ClinicalTrials.gov Identifier: NCT03558503 |
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Recruitment Status :
Completed
First Posted : June 15, 2018
Results First Posted : July 25, 2022
Last Update Posted : September 16, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Bladder Cancer Urothelial Carcinoma Urothelial Carcinoma Bladder | Drug: UGN-102 | Phase 2 |
Eligible patients were treated with 6 once-weekly intravesical instillations of UGN-102.
The ablative effect of UGN-102 was evaluated at the 3-month Visit, which occurred 5 weeks ± 1 week after the last weekly instillation (3 months after initiation of study drug). Response was determined based on visual evaluation by cystoscopy (appearance, number, and size of the lesions) and, if there were remaining lesions, by histopathology of the remaining lesions. Complete response (CR) was defined as having no detectable disease (NDD) and was assessed visually during cystoscopy and also by urine cytology. In the event that the investigator was not sure, and there was suspect tissue, a small biopsy was taken from the suspect tissue to confirm CR in addition to cystoscopy and urine cytology.
Patients who achieved a CR continued to have monthly telephone contacts to document any adverse events (AEs) and changes in concomitant medications and were assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence of disease recurrence. Patients who had a non-complete response (non-CR) discontinued the study and continued with standard of care according to their treating physician.
Safety was determined based on a review of AEs, laboratory assessments, and physical examination findings.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 63 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2b, Single-Arm, Multicenter Trial to Evaluate the Efficacy and Safety of UGN-102 as Primary Chemoablative Therapy in Patients With Low Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk of Recurrence |
| Actual Study Start Date : | October 15, 2018 |
| Actual Primary Completion Date : | January 3, 2020 |
| Actual Study Completion Date : | October 21, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: UGN-102
Patients were treated with 6 once-weekly intravesical instillations of UGN-102.
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Drug: UGN-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, with subsequent conversion to a semi-solid gel depot following instillation into the bladder. The UGN-102 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL). Other Name: UGN-102 (mitomycin) for intravesical solution |
- Complete Response (CR) Rate for UGN-102 Treatment [ Time Frame: 3 months after the first instillation of UGN-102 ]To evaluate the tumor ablative effect of UGN-102 in patients with LG NMIBC. CR rate was defined as the percentage of patients with no detectable disease (NDD) as determined by cystoscopy, for cause biopsy, and urine cytology.
- Durable Complete Response (DCR) Rate [ Time Frame: 6, 9, and 12 months after the first instillation of UGN-102 ]To evaluate the durability of response in patients with LG NMIBC who achieve CR. DCR rate was defined as the percentage of patients who maintained CR at the respective time point.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. [ Time Frame: Up to 12 months ]The number of patients with each type of event will be summarized. Adverse event severity was graded according to Common Terminology Criteria for Adverse Events version 5.0 as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), Grade 5 (fatal).
- Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values [ Time Frame: Up to 12 months ]The number of patients who met PCS criteria for chemistry or hematology parameters post-baseline will be summarized
- Number of Participants With Post-baseline PCS Vital Signs Values [ Time Frame: Up to 12 months ]The number of patients who met PCS criteria for vital signs parameters post-baseline will be summarized
- Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings [ Time Frame: Up to 12 months ]The number of patients with abnormal, CS physical examination findings post-baseline will be summarized
- Number of Participants With Post-baseline CS Urology-oriented Physical Examination Findings [ Time Frame: Up to 12 months ]The number of patients with abnormal, CS urology-oriented physical examination findings post-baseline will be summarized
- Mitomycin Plasma Concentrations [ Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102 ]Mitomycin plasma concentrations were assessed in a subset of 6 patients treated with UGN-102
- Mitomycin Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 0 (pre-instillation) to 6 hours after the first instillation of UGN-102 ]Mitomycin AUC was assessed in a subset of 6 patients treated with UGN-102
- Mitomycin Maximum Plasma Concentration (Cmax) [ Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102 ]Mitomycin Cmax was assessed in a subset of 6 patients treated with UGN-102
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Willing and able to sign an informed consent and comply with the protocol.
- Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 6 weeks of screening.
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Is at intermediate risk of recurrence, 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).
- Has negative voiding cytology for high grade (HG) disease at or within 6 weeks of enrollment.
- Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the participant is female or the female partner of a male participant and is of childbearing potential (defined as premenopausal women who have not been sterilized).
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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 (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
- Alkaline phosphatase ≤ 2.5 × ULN;
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
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Has no evidence of active urinary tract infection (UTI) at Screening and Baseline visits.
- In the case of symptomatic UTI, the patient will be treated with a full course of antibiotics, and study drug will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study drug is left to the discretion of the Principal Investigator (PI).
Exclusion Criteria:
- History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment.
- Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 2 years.
- History of HG papillary UC in the past 2 years.
- Known allergy or sensitivity to mitomycin.
- Clinically significant urethral stricture that would preclude passage of a urethral catheter.
- History of pelvic radiotherapy.
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History of:
- Neurogenic bladder;
- Active urinary retention;
- Any other condition that would prohibit normal voiding.
- Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract urothelial carcinoma (UTUC).
- Has participated in a study with an investigational agent or device within 30 days of enrollment.
- History of prior treatment with an intravesical chemotherapeutic agent with the exception of a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT).
- 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.
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): NCT03558503
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| Study Director: | Elyse Seltzer, MD | UroGen Pharma |
Documents provided by UroGen Pharma Ltd.:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | UroGen Pharma Ltd. |
| ClinicalTrials.gov Identifier: | NCT03558503 |
| Other Study ID Numbers: |
TC-BC-12 |
| First Posted: | June 15, 2018 Key Record Dates |
| Results First Posted: | July 25, 2022 |
| Last Update Posted: | September 16, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Non-muscle invasive bladder cancer Low grade non-muscle invasive bladder cancer Intermediate risk non-muscle invasive bladder cancer |
NMIBC UGN-102 Mitomycin |
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Carcinoma Urinary Bladder Neoplasms Carcinoma, Transitional Cell Non-Muscle Invasive Bladder Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications |
Urogenital Diseases Urinary Bladder Diseases Urologic Diseases Male Urogenital Diseases Mitomycins Mitomycin Antibiotics, Antineoplastic Antineoplastic Agents Alkylating Agents Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors |