A Phase I, Open-Label, Multicentre Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD5312 in Patients With Advanced Solid Tumours Where the Androgen Receptor Pathway is a Potential Factor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose of AZD5312 in patients with advanced solid tumours where androgen receptor pathway is a potential factor.
研究概览
简要总结
This is a first time in man (FTIM), Phase I study to determine the Maximum Tolerated Dose, Recommended Phase 2 Dose, safety, tolerability and Pharmacokinetics of AZD5312. This is a multicentre study with sites in the United States and United Kingdom. Approximately 90 patients are expected to be enrolled in this study.
The study involves two parts, Part A, Dose Escalation and Part B, Dose Expansion.
详细描述
This is a first time in man (FTIM), Phase I study to determine the Maxiimum Tolerated Dose, Recommended Phase 2 Dose, safety, tolerability and Pharmacokinetics of AZD5312. This is a multicentre study with sites in the United States and United Kingdom. Approximately 90 patients are expected to be enrolled in this study.The study involves two parts, Part A, Dose Escalation and Part B, Dose Expansion.
AZD5312 will be given intravenously (IV) as an infusion, over one hour. For the purpose of planning, each 4 week period (28 days) will be called a Cycle. AZD5312 will initially be administered 4 times within the first 11 days, (on Days [1, 4, 8 and 11]± 2), with no dosing on sequential days. Patients will receive weekly treatments on Days 15 and 22 to complete Cycle.
- During the subsequent cycles, patients will receive weekly treatment on Days 1, 8, 15 and 22 (±2). The AZD5312 dose will not change unless dose reductions are required due to treatment-related toxicity. Patients will continue to receive AZD5312 until disease progression, intolerable toxicity, or discontinuation criteria have been met. Toxicity, Pharmacokinetics and biomarker data will be assessed throughout the study. Alternative infusion durations and/or treatment schedules may be explored if preliminary data suggest these would be more appropriate.
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 130 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
AZD5312
AZD5312 will be given intravenously (IV) as an infusion, over one hour. For the purpose of planning, each 4 week period (28 days) will be called a Cycle. AZD5312 will initially be administered 4 times within the first 11 days, (on Days [1, 4, 8 and 11]± 2), with no dosing on sequential days. Patients will receive weekly treatments on Days 15 and 22 to complete Cycle
- During the subsequent cycles, patients will receive weekly treatment on Days 1, 8, 15 and 22 (±2).
干预措施: AZD5312 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose of AZD5312 in patients with advanced solid tumours where androgen receptor pathway is a potential factor.
时间窗: 13 Months
•3 evaluable patients (pts) will be enrolled at each dose level (3+3 design) •Evaluated for 28 days before escalation to next dose level. •If more than 1 experiences Dose Limiting Toxicity (DLT), additional 3 patients treated with the same dose. •Maximum of 6 pts enrolled per dose level. •100% increase in dosing until 2 pts (out of 3) at dose level experience toxicity of ≥ Grade 2, or 1 pt. experiences DLT. •Accelerated titration stopped, and subsequent dose escalation will be ≤ 50%. •Evaluation of a cohort of at least 3 patients completing 1 cycle of treatment (28 days) required prior to next dose level. •Dose escalation decisions take into account safety profile of prior dose groups, and available PK data. •Additional patients may be enrolled at lower doses for sufficient PK data. •Intermediate dose levels evaluated to declare the recommended Phase II dose (RP2D). When R2PD is determined, 12 patients will be treated at that dose level to further evaluate safety and efficacy.
Safety and tolerability of AZD5312 in patients assessed in terms of AEs, labs, vitals, ECGs and conc. med use.
时间窗: 13 months
Maximum Tolerated Dose of AZD5312 in pts with advanced solid tumours where androgen receptor pathway is a potential factor.
时间窗: 13 months
The patient population used for determination of the MTD will consist of patients who have met the minimum safety evaluation requirements of the study, and/or who have experienced a DLT. Minimum safety requirements will be met if, during Cycle 1 of treatment, the patient receives all doses of AZD5312, completes all required safety evaluations, and is observed for at least 28 days following the first dose of AZD5312.
次要结局
- Pharmacokinetics of AZD5312 determined by AUC(0-t)(25 Months)
- Pharmacokinetics of AZD5312 determined by λz(25 months)
- Pharmacokinetics of AZD5312 determined by t½λz(25 months)
- Pharmacokinetics of AZD5312 determined by (AUC(0-24)(25 months)
- PK of AZD5312 determined Vz(25 months)
- Pharmacokinetics of AZD5312 determined by MRT(25 Months)
- Pharmacokinetics of AZD5312 determined by CLR(25 Months)
- Pharmacokinetics of AZD5312 determined by Cmax(25 months)
- Pharmacokinetics of AZD5312 determined by Css min(25 Months)
- Pharmacokinetics of AZD5312 determined by tmax(25 months)
- Preliminary anti-tumour activity of AZD5312 in patients with advanced solid tumours.(25 months)
- Pharmacokinetics of AZD5312 determined by AUC(25 months)
- Pharmacokinetics of AZD5312 determined by CL(25 months)
- Pharmacokinetics of AZD5312 determined by tss max(25 Months)
- Pharmacokinetics of AZD5312 determined by Ae;%dose(25 Months)
- Pharmacokinetics of AZD5312 determined byAUCss(25 Months)
- Pharmacokinetics of AZD5312 determined by Css max(25 Months)
- Pharmacokinetics of AZD5312 determined by CLss(25 Months)
- Pharmacokinetics of AZD5312 determined by RAC(25 Months)