A Phase 1 Study to Evaluate the Safety and Clinical Activity of Intravesicular CAVATAK (Coxsackievirus A21, CVA21) Alone and in Sequential Combination With Low Dose Mitomycin C in Patients With Non-Muscle Invasive Bladder Cancer (VLA-012 CANON)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
研究概览
简要总结
The study consisted of 2 sequential parts. Part A assessed the safety and tolerability of CAVATAK administered via intravesical instillation in patients with non-muscle invasive bladder cancer scheduled to undergo TUR. Part B assessed the safety and tolerability of CAVATAK administered in sequential combination with low dose Mitomycin C in the same patient population.
详细描述
This was a Phase I, two-part, open-label, dose-escalation study designed to evaluate CVA21 alone and in sequential combination with low-dose mitomycin C in patients with non-muscle invasive bladder cancer (NMIBC) who were candidates for and were planning to undergo TUR for treatment of their disease. This gave a relatively homogeneous study population and facilitated collection of resected tumour tissue for histological, pharmacodynamics (PD) and pharmacokinetic (PK) analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Clinical diagnosis of NMIBC based on cystoscopic appearance
- •No intravesical therapy within 6 weeks of study entry
- •No prior radiation to the pelvis
- •ANC >1500/mm³; Hb >9.0 g/dL; Platelet >100000/mm³
- •Serum creatinine ≤ 1.5 mg/dL
- •Bilirubin within normal limits; AST ≤ 2.5x upper limit of normal (ULN); ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5x ULN unless bone metastasis is present in the absence of liver metastasis
- •INR < 1.2; aPPT = 0.8-1.2; PT = 0.9-1.8
- •Candidate for TUR and planning to undergo TUR
- •Negative pregnancy test within 7 days of treatment start
- •Patients of child-bearing potential must agree to use an effective method of birth control
排除标准
- •Prior local or systemic treatments for NMIBC
- •Concurrent treatment with any chemotherapeutic agent
- •Patients not deemed acceptable for general anaesthesia
- •Women who are pregnant or lactating
- •History of vesicoureteric reflux or an indwelling urinary stent
- •Administration of an investigational agent within 3 months of study entry
- •Active cardiac disease
- •Known infection with HIV, hepatitis B or C
- •Active uncontrolled infection
研究组 & 干预措施
CVA21
CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.
干预措施: CVA21 (Biological)
CVA21/Mitomycin C
Mitomycin C (MMC) was administered at 10 mg by intravesical instillation on Day 1. Four hours after instillation of MMC, CVA21 was administered by intravesical instillation of one of 2 ascending dose levels or schedules. Subjects received a second instillation of CVA21 alone on Day 2 without pretreatment with MMC.
干预措施: CVA21 (Biological)
CVA21/Mitomycin C
Mitomycin C (MMC) was administered at 10 mg by intravesical instillation on Day 1. Four hours after instillation of MMC, CVA21 was administered by intravesical instillation of one of 2 ascending dose levels or schedules. Subjects received a second instillation of CVA21 alone on Day 2 without pretreatment with MMC.
干预措施: Mitomycin C (Drug)
结局指标
主要结局
Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
时间窗: 30 days from last dose
Number of Participants with Treatment-emergent adverse events. The events for each cohort of dose of CVA21 only are pooled for the analysis.
次要结局
未报告次要终点