PIPA: A Phase Ib Study to Assess the Safety, Tolerability and Efficacy of the PI3K Inhibitors, Taselisib (GDC-0032) or Pictilisib (GDC-0941), in Combination With PAlbociclib, With the Subsequent Addition of Fulvestrant in PIK3CA-mutant Breast Cancers
试验速览
- 阶段
- 1 期
- 入组人数
- 93
- 试验地点
- 2
- 主要终点
- Preliminary anti-tumour assessment of triplet combination (RECIST criteria version 1.1) in patients with PIK3CA mutant advanced ER+ve HER2-ve breast cancer.
研究概览
简要总结
Part A: This is a phase Ib trial combining the CDK4/6 inhibitor palbociclib with the PI3K inhibitors taselisib, or pictilisib. There are two treatment arms during the dose escalation phase where patients will receive either taselisib OR pictilisib in combination with palbociclib. Palbociclib, taselisib and pictilisib can all be given orally once daily with food, in a 21-days-on and 7-days-off schedule. Once the MTD is reached, the combination with the optimum safety and PK/PD profile will be taken forward to the dose expansion phase (Part B).
Part B1: At the MTD dose expansion, fulvestrant will be administered in addition to palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule in the ER+ve HER2-ve PIK3CA mutant breast cancer cohort. Fulvestrant will be given intramuscularly on Day 1, Day 15 in cycle one followed by Day 1 for all subsequent cycles.
Part B2: At the MTD dose expansion, patients with PIK3CA mutant advanced solid tumours will be treated with palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule.
详细描述
This is a phase Ib trial of palbociclib in combination with either taselisib or pictilisib. The study will include a dose escalation phase (Part A), and an MTD dose expansion phase (Part B).
Part A: will investigate escalating doses of palbociclib with either pictilisib or taselisib administered orally, continuously for 21 days out of a 28 day cycle in patients with advanced solid tumours recruited simultaneously into two parallel arms (up to 24 patients in each arm with a maximum of 48 patients in Part A).
Once the MTD is determined the combination with the optimum safety and PK/PD profile as determined by the SRC will be taken forward to the dose expansion phase (Part B).
Part B: The MTD dose expansion phase will be conducted using the optimal combination from Part A in two parallel arms as follows:
B1: Patients (n=25) with PIK3CA mutant ER + HER2-ve advanced breast cancers will be treated with a triplet combination of palbociclib and either taselisib or pictilisib along with fulvestrant. Part B1 will require at least two of the first 15 patients to respond to progress to recruit the full 25 patients.
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
- 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
Palbociclib + Taselisib
The starting dose of palbociclib in combination with taselisib will be 100mg OD of palbociclib and 2mg taselisib OD, administered orally 21-days-on and 7-days-off, as part of a 28 day cycle.
干预措施: Palbociclib + Taselisib / Pictilisib (Drug)
Palbociclib + Pictilisib
The starting dose of palbociclib in combination with pictilisib will be 100mg OD of palbociclib and 195 mg pictilisib OD, administered orally 21-days-on and 7-days-off, as part of a 28 day cycle.
干预措施: Palbociclib + Taselisib / Pictilisib (Drug)
结局指标
主要结局
Preliminary anti-tumour assessment of triplet combination (RECIST criteria version 1.1) in patients with PIK3CA mutant advanced ER+ve HER2-ve breast cancer.
时间窗: duration of study (24 months)
To evaluate disease response by RECIST criteria version 1.1, clinical benefit rate, best change in tumour size, progression free survival, and duration or response.
Recommended dose for Phase II
时间窗: duration of study (24 months)
To determine a dose at which no more than one patient out of up to six patients at the same dose level experience a highly probable or probable drug-related dose limiting toxicity.
Safety and Toxicity Profile (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0)
时间窗: duration of study (24 months)
To evaluate causality of each adverse event to palbociclib with taselisib and fulvestrant; palbociclib and taselisib; letrozole, palbociclib and taselisib against CTCAE criteria V4.0
次要结局
- Pharmaockinetics Profile (AUC0-24 and Cmax)(duration of study (24 months))