A Phase I/II Multicenter Study of the Combination of AZD2014 and Palbociclib on a Background of Hormonal Therapy in Patients With Locally Advanced/Metastatic Estrogen Receptor Positive Breast Cancer Comprising a Safety, Pharmacokinetic and Preliminary Efficacy Evaluation Followed by a Randomized, Double-Blind, Placebo-controlled, Parallel Group Extension (PASTOR).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Parts A and B: Number of adverse events experienced by patients
研究概览
简要总结
This dose finding/extension study was designed originally to consist of three parts: Part A was intended to identify the MTD of the AZD2014/ palbociclib combination on a background of fulvestrant (referred to as the triplet) in postmenopausal women with locally advanced/ metastatic estrogen receptor positive (ER+) breast cancer. Part B was to further characterize safety, tolerability, PK, and preliminary efficacy in single-arm dose expansion groups. Part C was to be a Phase 2, randomized, double-blind, extension comparing the triplet and doublet combinations. Part C was deleted from the protocol and was not performed.
详细描述
This dose finding/extension study was designed originally to consist of three parts:
Part A is a Phase 1 triplet-dose finding investigation in 3-6 patients per cohort to determine the maximum tolerated dose (MTD) of the triplet.
Part B is a single arm expansion in approximately 27 patients evaluable for response to define the recommended Phase 2 dose (RP2D).
Part C was intended to investigate the efficacy of the triplet combination at the RP2D in a randomized, double-blind, placebo-controlled, stratified, parallel group extension. Part C was intended to include ER+, locally advanced and/or metastatic breast cancer patients who have progressed following prior non-steroidal aromatase inhibitor (NSAI) endocrine therapy. Patients in Part C were to be randomized to receive either the triplet combination (AZD2014 + palbociclib + fulvestrant) or the doublet (matching AZD2014 placebo + palbociclib + fulvestrant). Patients were to be stratified according to hormone sensitivity, presence of visceral metastases, and prior CDK inhibitor treatment. Part C would have been conducted if indicated by the emerging data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Study was originally designed as randomized and double blinded. Currently (CSP v.8.0 of 14-Dec-2021) no masking and no randomization is planned.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Female
- 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
Triplet Combination (Dose Finding)
Phase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet.
干预措施: AZD2014 (Drug)
Triplet Combination (Dose Finding)
Phase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet.
干预措施: Palbociclib (Drug)
Triplet Combination (Dose Finding)
Phase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet.
干预措施: Fulvestrant (Drug)
Triplet Combination (Dose Expansion)
Additional patients will be enrolled at the dose determined in Part A.
干预措施: AZD2014 (Drug)
Triplet Combination (Dose Expansion)
Additional patients will be enrolled at the dose determined in Part A.
干预措施: Palbociclib (Drug)
Triplet Combination (Dose Expansion)
Additional patients will be enrolled at the dose determined in Part A.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Parts A and B: Number of adverse events experienced by patients
时间窗: Approximately 16 months
Safety and tolerability assessed through the incidence of adverse events.
次要结局
- Part B: Duration of Response (DoR)(Assessed every 8 weeks for approximately 16 months)
- Parts A and B: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following multiple doses(Samples will be collected at prespecified time points up to 12 hours following dosing.)
- Time to reach peak plasma concentrations (tmax) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 12 hours following dosing.)
- Part B: Overall Survival (OS)(Approximately 24 months)
- Parts A and B: Best Objective Response (BOR)(Assessed every 8 weeks for approximately 16 months)
- Part A: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following single dose(Samples for single dose PK will be collected at prespecified time points up to 12 hours following dosing.)
- Area under the plasma concentration-time curve from zero to infinity (AUC 0-∞) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 9 days following dosing.)
- Area under the plasma concentration-time curve from zero to 12 hours (AUC 0-12) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 12 hours following dosing.)
- Area under the plasma concentration-time curve from zero to 24 hours (AUC 0-24) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 24 hours following dosing.)
- Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC 0-t) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 9 days following dosing.)
- Part B: Progression Free Survival (PFS)(Assessed every 8 weeks for approximately 16 months)
- Parts A and B: Objective Response Rate (ORR)(Assessed every 8 weeks for approximately 16 months)
- Parts A and B: Change from baseline in biomarker H-score(16 months)
- Terminal elimination rate constant (λz) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 9 days following dosing.)
- Terminal plasma half-life (t1/2λz) for AZD 2014 and palbociclib.(Samples will be collected at prespecified time points up to 9 days following dosing.)