Phase 2/3 Run in, Open-Label, Two Arm Study for Safety, Efficacy and Tolerability of PRV111 (Cisplatin Transmucosal System) & PRV211 (Intraoperative Cisplatin System) in Subjects Amenable to Surgery
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Arm 1 ( Phase 2/3 Run in ):
PRV111: Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017)
Arm 2 (Phase 1) PRV211: Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting
Subject Assignment: Subjects will be assigned to Arm 1 or Arm 2 of this study based on disease staging Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity
详细描述
Methodology: This is a Phase 1/2, open-label, Safety and Efficacy, Tolerability, Anti-Tumor Effects, Systemic Exposure, and Device Technical Effects of PRV211 (Intraoperative Cisplatin System) in subjects with T2-T3 oral squamous cell carcinoma (SCC) amenable to surgery.
Study Design: This study will enroll up to 40 subjects. An interim analysis will take place to evaluate safety and efficacy results and the addition of a second arm (see interim analysis section for further detail). In this study both safety and efficacy will be evaluated. All subjects will be monitored for possible DLTs.
For the purpose of dose selection, tolerable dose is defined as a dose where fewer than 33% of subjects being evaluated within the safety population present with dose-limiting toxicities (DLTs). Effective dose is determined based on the evaluable population as described in the Statistical Methods section.
The study is described below:
Up to 15 subjects will be enrolled for stage 1 and undergo 1 PRV211 treatment application during standard of care tumor resection surgery. Each treatment will include permeation enhancer. If 5 or less respond, the dose can be escalated given safety requirements are met.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity
PRV111 Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017)
干预措施: PRV111 (Cisplatin Transmucosal System) (Drug)
Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity
Arm 2 PRV211 Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting
干预措施: PRV211 (Intraoperative Cisplatin System) (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 6-7 months
Proportion of treated tumors that have a response to PRV111 treatment. Response is defined as either or both: 1) histopathological downgrade of the disease such as partial or complete response as determined by post-treatment biopsies compared to baseline, or 2) clinically measurable tumor volume reduction from baseline of 30% or more from baseline.
Safety assessed via dose-limiting toxicities
时间窗: 1-month post-surgery and through study completion, ~12-14 months
Determine a safe dose of PRV211 (Intraoperative Cisplatin System) under the conditions of the trial. For the purpose of safety detection, if greater than 33% of subjects being evaluated for safety present with dose-limiting toxicities (DLTs), the study drug is deemed unsafe.
次要结局
- Event Free Survival(through study completion, ~12-14 months)
- Pharmacokinetics: platinum levels in blood(through study completion, ~12-14 months)