A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity,Safety,Tolerability,and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)(PYRUS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
研究概览
简要总结
To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy, in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated in patients who have progressed after chemotherapy (Part A) and in patients who have progressed before receiving chemotherapy (Part B).
Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off).
Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients on a dose and schedule selected from Part A.
详细描述
A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety, Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) (PYRUS)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent
- •Males aged 18 years and older
- •Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features for which no standard therapy is currently considered appropriate
- •Documented evidence of Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
- •Part A: Patients must have received prior docetaxel-based chemotherapy for mCRPC and have a Circulating Tumour Cell score of 5;
- •Part B: Patients must have progressed before receiving any chemotherapy for mCRPC;
排除标准
- •Any prior exposure to agents which inhibit AKT as the primary pharmacological activity
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus
- •Spinal cord compression or brain metastases unless asymptomatic, treated, and stable and not requiring steroids
- •Clinically significant abnormalities of glucose metabolism
- •Major surgery within the previous 4 weeks
研究组 & 干预措施
Part A Group 1 Intermittent
Recruitment suspended and will not be re-opened. See intervention description below.
干预措施: Intermittent dosing of AZD5363 (Drug)
Part A Group 2 Intermittent
Recruitment complete. See intervention description below.
干预措施: Intermittent dosing of AZD5363 (Drug)
Part B
This part of the study will not be conducted following a review of data from Part A. See intervention description below.
干预措施: Intermittent dosing of AZD5363 (Drug)
结局指标
主要结局
Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
时间窗: PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks
Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
时间窗: CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks
Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
时间窗: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent
Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
时间窗: Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.
次要结局
- Parts A and B: Safety and tolerability of AZD5363 in terms of adverse events, serious adverse events (including death) and safety measures: ECG, ECHO/MUGA, physical examination, pulse, blood pressure, weight and laboratory variables(Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.)
- Parts A and B: AZD5363 PK: time to maximum plasma concentration, terminal rate constant,terminal half life, area under plasma concentration time curve, plasma clearance & volume of distribution(Multiple AZD5363 PK blood sample assessments.AZD5363 plasma concentration blood samples will be taken on Day 1(pre-dose,2,4,8 hours post-dose);D2(pre-dose);D8(continous) or D11(intermittent) (pre-dose and at 2,4,and 8 hours post-dose);D15,Cyc)
- Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker(Multiple PD blood sample assessments.PD blood samples will be taken on the same schedule as PK sample and then Day 1 of every 12 weeks thereafter, and at the discontinuation visit)
- Parts A and B: Progression-free survival (PFS)(Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.)
- Parts A and B: Quality of life (QoL)(QOL will be documented from date of randomization and for 12 weeks.)