A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG-IR-NMIBC)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 282
- 试验地点
- 137
- 主要终点
- Disease-free Survival (DFS)
研究概览
简要总结
This global, randomized, controlled, open-label Phase 3 study was designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
详细描述
Eligible patients were randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization was stratified by the presence of a previous LG-NMIBC episode within 1 year of the current diagnosis (yes or no). Starting on Day 1, patients randomized to the UGN-102 ± TURBT arm will receive 6 weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone arm underwent TURBT.
All patients returned to the clinic approximately 3 months after the start of treatment for a disease assessment visit. Response to treatment was determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions, and voiding urine cytology. Patients confirmed to have a complete response (CR), defined as having no detectable disease (NDD) in the bladder, received no further treatment and entered the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) due to residual LG disease in either treatment arm underwent TURBT of any remaining lesions and then entered the Follow-up Period of the study.
During the Follow-up Period, patients returned to the clinic every 3 months to determine if they remained disease free. Patients remained on study until completion of all follow-up visits or until disease recurrence, disease progression, or death was documented, whichever occurred first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit were considered to have completed the study and released to the care of their treating physician.
Study enrollment was stopped early by the sponsor to pursue an alternative development strategy for UGN-102 in the treatment of bladder cancer. Patients who had consented at the time the trial terminated were permitted to continue, but follow-up was terminated once the last patient had been followed for 15 months after the start of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
- •Patient who has newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks of Screening.
- •Has intermediate risk 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).
- •Negative voiding cytology for HG disease within 6 weeks of Screening.
- •Has adequate organ and bone marrow function as determined by the following routine laboratory tests:
- •Leukocytes ≥ 3,000 cells per μL;
- •Absolute neutrophil count ≥ 1,500 cells 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 (ALP) ≤ 2.5 × ULN;
- •Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
- •Has no evidence of active urinary tract infection (UTI).
- •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 enrollment through 6 months post-treatment.
排除标准
- •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 1 year.
- •History of HG papillary UC in the past 2 years.
- •Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed.
- •Clinically significant urethral stricture that would preclude passage of a urethral catheter.
- •History of pelvic radiotherapy.
- •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 UC.
- •Current tumor stage of T
- •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.
- •History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately after any previous TURBT.
- •Has previously participated in a study in which they received UGN-
- •Has participated in a study with an investigational agent or device within 30 days of randomization.
研究组 & 干预措施
UGN-102 ± TURBT
6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102).
干预措施: UGN-102 (Drug)
UGN-102 ± TURBT
6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102).
干预措施: TURBT (Procedure)
TURBT Alone
TURBT on Day 1 + repeat TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the initial TURBT).
干预措施: TURBT (Procedure)
结局指标
主要结局
Disease-free Survival (DFS)
时间窗: 15 months
DFS is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), progression to high-grade (HG) disease, or death due to any cause. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization.
次要结局
- Duration of Response (DOR)(12 months)
- Number of TURBTs(3 months)
- Number of Participants With Post-baseline PCS Serum Chemistry Values(Up to 6 months)
- Time to Recurrence (TTR)(15 months)
- Complete Response Rate (CRR)(3 months)
- Changes From Baseline in Health-related Quality of Life(Pre-treatment to 3 months after the start of treatment)
- Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values(Up to 6 months)
- Observed CRR at Scheduled Disease Assessment Time Points(12 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest(Up to 21 months)