E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Muscle Invasive Bladder Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy (both superiority and non-inferiority) of UGN-102 with or without TURBT versus TURBT alone with respect to disease-free survival (DFS) in patients with Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG IR-NMIBC). |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of UGN-102 with or without TURBT versus TURBT alone with respect to: a) Time to Recurrence (TTR) b) Complete Response Rate (CRR) at 3-Month disease assessment c) Duration of Response (DOR) d) Avoid of surgery (TURBT) for treatment of LG IR-NMIBC 2. To evaluate the safety profile of UGN-102 with or without TURBT versus TURBT alone. 3. To assess the effect of UGN-102 with or without TURBT versus TURBT alone on Patient Reported Outcomes (PROs) including disease related symptoms, functioning, and health-related quality of life (HRQoL). 4. To evaluate visit level Complete Response Rate (CRR) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 8 weeks of screening; 2. Is at intermediate risk for progression, defined as having 1 or 2 of the following: a. presence of multiple tumors b. solitary tumor > 3 cm c. recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at initial Screening Visit) 3. Negative voiding cytology for high grade (HG) disease within 6 weeks of screening; 4. 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 mg/dL • Total bilirubin ≤ 1.5 upper limit of normal (ULN) • Aspartate aminotransferase (AST) (Serum glutamic oxaloacetic transaminase [SGOT])/Alanine aminotransferase (ALT) (Serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN • Alkaline phosphatase (ALP) ≤ 2.5 × ULN • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min; 5. Has no evidence of active urinary tract infection (UTI); |
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E.4 | Principal exclusion criteria |
1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment; 2. Received Bacille de Calmette et Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year; 3. History of HG papillary UC in the past 2 years; 4. History of: a. neurogenic bladder b. active urinary retention c. any other condition that would prohibit normal voiding 5. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic UC or concurrent upper tract urothelial carcinoma (UTUC); 6. Current tumor grading of T1; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease-free survival (DFS) is defined in the same way in treatment and control arms, however, it is defined differently between complete responders (CR) and non-complete responders (NCR) at 3-Month disease assessment. For patients who have a CR at 3-Month, DFS is defined as the time from randomization until the earliest date of disease recurrence or death due to any cause. Patients who do not have a CR at 3-Month will be treated with TURBT in both arms and DFS is defined as the time from this TURBT until the earliest date of disease recurrence or death due to any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The following efficacy endpoints will be evaluated: a) Time to recurrence (TTR) is defined in the same way in treatment and control arms, however, it is defined differently between complete responders (CR) and non-complete responders (NCR) at 3-Month disease assessment. For patients who have a CR at 3-Month, TTR is defined as the time from randomization to first documented disease recurrence. Patients who do not have a CR at 3-Month will be treated with TURBT in both arms and TTR is defined as the time from this TURBT to first documented disease recurrence. b) Complete response rate (CRR), defined as the proportion of patients who achieved CR at the 3-Month disease assessment. c) Duration of response (DOR), defined as the time from first documented CR to the date of first documented disease recurrence or death due to any cause among patients who achieve a CR at the 3-Month disease assessment. d) Proportion of patients requiring TURBT in each arm and average number of TURBT interventions per patient in each arm 2. The safety profile of UGN-102 and TURBT will be evaluated as assessed through standard clinical and laboratory tests (hematology and chemistry, urinalysis, physical examination, vital sign measurements, diagnostic tests, etc.) and through the collection of reports of adverse events (AEs) and serious adverse events (SAEs) including AEs of special interest. 3. Changes from baseline in HRQoL measures assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Non-muscle Invasive Bladder Cancer patients (EORTC-QLQ-NMIBC24). 4. Observed CRR at scheduled disease assessment timepoints, defined as the proportion of patients who had CR at 3-Month disease assessment and maintained CR up to that particular follow-up disease assessment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Transurethral Resection of Bladder Tumors (TURBT) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Georgia |
Israel |
Russian Federation |
Serbia |
Ukraine |
United States |
Bulgaria |
Estonia |
Hungary |
Latvia |
Poland |
Romania |
Slovakia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |