A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 4
- 主要终点
- Incidence of Dose limiting toxicities (DLTs) - Phase lb only
研究概览
简要总结
The purpose of this trial is to explore the clinical utility of the three investigational agents in HR+, HER2- breast cancer. LEE011 (CDK4/6 inhibitor), BKM120 (PI3K-pan class I-inhibitor) and BYL719 (PI3K-alpha specific class I inhibitor) in combination with fulvestrant.
This is a multi-center, open-label Phase Ib/II study. The Phase Ib portion of the study is a dose escalation to estimate the MTD and/or RP2D for three regimens: LEE011 with fulvestrant; LEE011 and BKM120 with fulvestrant; LEE011and BYL719 with fulvestrant.
The Phase II portion of the study was planned to be a randomized study to assess the anti-tumor activity as well as safety and tolerability of LEE011 with fulvestrant to LEE011 and BKM120 with fulvestrant, and LEE011 and BYL719 with fulvestrant in patients with ER+/HER2- locally advanced or metastatic breast cancer.
Approximately 216 adult women with ER+/HER2- locally advanced or metastatic breast cancer were planned to be enrolled.
详细描述
On 31-May-2016 Novartis's made the decision decision to not open the Phase II portion of the study, for business reasons. Sufficient data had already been collected and no additional data for the triplet combinations was needed. As a result, the Phase II portion of the trial was not opened.
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
- •Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)
- •Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)
排除标准
- •HER2-overexpression in the patient's tumor tissue
- •Inadequate bone marrow function or evidence of end-organ damage
- •Severe or uncontrolled medical issues
- •Diabetes mellitus
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LEE011 + BKM120 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: LEE011 (Drug)
LEE011 + BKM120 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: fulvestrant (Drug)
LEE011 + BKM120 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: BKM120 (Drug)
LEE011 + BYL719 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: LEE011 (Drug)
LEE011 + BYL719 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: BYL719 (Drug)
LEE011 + BYL719 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: fulvestrant (Drug)
LEE011 + fulvestrant
LEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: LEE011 (Drug)
LEE011 + fulvestrant
LEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
干预措施: fulvestrant (Drug)
结局指标
主要结局
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
时间窗: 28 days
Dose limiting toxicities
Progression free survival (PFS) - Phase ll only
时间窗: 36 months
Progression Free Survival per RECIST v 1.1 by local investigator assessment
次要结局
- Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant(36 months)
- Overall Response Rate (ORR)(36 months)
- Progression Free Survival (PFS) (phase l only)(36 months)
- Duration of Response (DOR)(36 months)
- Overall Survival (OS) - Phase II only(36 months)
- Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.(36 months)