An International Multicentre, Open-Label First in Human Phase I/II Study to Evaluate the Safety, Tolerability, Biodistribution and Antitumour Activity of 177Lu-3BP-227 for the Treatment of Subjects With Solid Tumours Expressing Neurotensin Receptor 1
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Ipsen
- 入组人数
- 14
- 试验地点
- 8
- 主要终点
- Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)
研究概览
简要总结
This study was conducted to advance new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1). This study was the first time the investigational drug called 177Lu-3BP-227 was administered to patients under controlled conditions of a clinical study.
The purpose of this study was to evaluate how safe the investigational drug is as well to verify how well it is tolerated by patients after several intravenous administrations. In addition, the effect of the study drug on tumoral lesions and how it distributes throughout the body and at which rate it is removed from the body was evaluated. Since 177Lu-3BP-227 is a radio-labelled drug, it also measured how the emitted radiation is distributed throughout the body (dosimetry).
The study consisted of a phase I dose escalation part. The study originally planned to include a phase II study however due to early termination (not due to safety concerns) the study did not progress to phase II and was stopped during phase I. For the phase I dose escalation part, it was anticipated that approximately 30 subjects will be included, in up to six escalation steps. No expansion cohorts were implemented.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
177Lu-3BP-227
Screening: 177Lu-IPN01087 - 25 µg 3BP-227 (IPN01087) per 1 GBq of 177Lu. 1 GBq in a total volume of 10 mL.
Treatment phase: 177Lu-IPN01087 - 2.5 to 7.5 GBq escalation dose of 177Lu-3BP-227 (IPN01087) in a total volume of 20 mL for each cycle of administration (2 cycles plus 4 optional additional).
干预措施: 177Lu-3BP-227 (also called 177Lu-IPN01087) (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
DLTs were defined for a list of predefined study medication-related adverse events (AEs) as specified in the protocol, according to the National Cancer Institute - Common Terminology Criteria for Adverse Events scale version 5.0 that occurred during the defined DLT assessment period (during Cycle 1 or 2).
次要结局
- Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.)
- Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.)
- Phase 1: Clearance of 3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: Number of Participants With Disease Control Rate (DCR)(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Renal Clearance of 3BP-227 From Plasma(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.)
- Phase 1: Half-life (t1/2) of 177Lu-3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.)
- Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Cmax of 3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: AUC of 3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: t1/2 of 3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: Progression-Free Survival (PFS)(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Overall Survival (OS)(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs(Measurements were performed at 0 to 1 hours, 2 to 4 hours, 16 to 24 hours, 40 to 48 hours, 72 to 96 hours post infusion in each treatment cycle.)
- Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Volume of Distribution of 3BP-227(Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1.)
- Phase 1: Number of Participants With Objective Response Rate (ORR)(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST(From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks.)
- Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen(Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal)
- Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9(Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal)