A Phase 1/2a Study of STM-416 Administered Intraoperatively to Patients Undergoing Transurethral Resection of Bladder Tumor (TURBT) for Recurrent High-Grade Papillary Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 75
- 试验地点
- 20
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) [Safety and Tolerability] Phase 1
研究概览
简要总结
This is a first-in-human (FIH), Phase 1/2a, multi center, open-label, single treatment, dose escalation and expansion study designed to determine the safety and tolerability of STM-416 in patients with bladder cancer.
详细描述
This is a 2-part, multicenter, first-in-human (FIH), Phase 1/2a study in patients with a history of pathologically confirmed high-grade Ta or T1 NMIBC without CIS who have completed SOC previously, with recurrent papillary disease seen on cystoscopy, and who are undergoing TURBT without perioperative intravesical chemotherapy. All patients will receive relevant SOC therapy following TURBT. SOC will be administered in the adjuvant setting.
Phase 1 is an open-label, single-treatment, dose-escalation study to evaluate the safety and tolerability of up to 6 increasing doses of intraoperatively administered STM-416 utilizing a 3+3 convention, with 3 to 6 patients enrolled in each STM-416 dose level, with a minimum of 6 patients enrolled at the highest dose level, for a total of approximately 30 patients.
Phase 2a is a randomized, single-blind, single-treatment, dose-expansion study that will comprise 2 arms: TURBT + STM-416 Dose 1 followed by SOC versus TURBT + STM-416 Dose 2 followed by SOC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Are aged 18 years or older;
- •Have a history of pathologically confirmed high-grade Ta or T1 NMIBC without CIS who have completed SOC previously, with recurrent papillary disease seen on cystoscopy, and who are undergoing TURBT without perioperative intravesical chemotherapy;
- •Are considered high risk for recurrence;
- •Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2;
- •Have adequate organ and marrow function as defined below:
- •Hemoglobin 9.0 g/dL;
- •Absolute neutrophil count 1.5 × 109/L (1500 per mm3);
- •Platelet count 75 × 109/L (75,000 per mm3);
- •Serum bilirubin 1.5 × institutional upper limit of normal (ULN);
- •AST (serum glutamic-oxaloacetic transaminase)/ALT (serum glutamic-pyruvic transaminase) 2.5 × institutional ULN; and
- •Creatinine CL 60 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine CL: Males: Creatinine CL (mL/min) = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL); or Females: Creatinine CL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL).
排除标准
- •Have a history of CIS or MIBC;
- •Are receiving any other investigational agents;
- •Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to resiquimod (R848), or excipients used in STM-416 including poloxamer 407 and sodium hyaluronate;
- •Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Urinary tract infections are not exclusionary unless they are NCI-CTCAE Grade 3 or higher;
- •Are a woman of childbearing potential regardless of contraceptive use; Note: Women of childbearing potential are only to be excluded in Phase 1 and Phase 2a to avoid bias due to the low prevalence of NMIBC in this population. However, they will be included in subsequent Phase 2/3 studies.
研究组 & 干预措施
STM-416
STM-416
干预措施: STM-416 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) [Safety and Tolerability] Phase 1
时间窗: 21 days
Incidence of dose-limiting toxicities (DLTs) over the first 21-days of study treatment
Recurrence free survival time (Phase 2a)
时间窗: Through study completion up to 24 months
Recurrence will be evaluated by cystoscopy and urine cytology
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Phase 1
时间窗: Time on trial up to 90 days
Incidence of serious adverse events (SAEs), and adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
次要结局
- Pharmacokinetics of STM-416 (Phase 1)(Day 0, post 24 hours, post 24 hour)
- Pharmacodynamics of STM-416(Day 0, post 24 hours, post 48 hours, post 21 days, post 90 days)
- Pharmacokinetics of STM-416 (Phase 1)(Day 0, post 24 hours, post 48 hour)