A Randomized, Double-blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 416
- 试验地点
- 22
- 主要终点
- Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)
研究概览
简要总结
This study evaluated whether the addition of daily BKM120 to weekly paclitaxel was effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.
详细描述
Based on the efficacy results at the time of the interim analyses, the DMC recommended stopping the study at Phase II during the interim as it met the protocol pre-specified futility criteria. Consequently, the Phase III portion of the study was not conducted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Breast cancer that is locally advanced or metastatic
- •HER2 negative disease, and a known hormone receptor status - ER/PgR (common breast cancer classification tests)
- •A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
- •Adequate bone marrow and organ function
- •Measurable or non-measurable disease
排除标准
- •Prior chemotherapy for locally advanced or metastatic disease
- •Previous treatment with PI3K or AKT inhibitors
- •Patient has symptomatic CNS metastases
- •Concurrent malignancy or malignancy within 3 years of study enrollment
- •Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to starting study drug
- •Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- •Active heart (cardiac) disease as defined in the protocol
- •Known hypersensitivity or contraindications to use paclitaxel
- •Pregnant or nursing (lactating) woman
- •Certain scores on an anxiety and depression mood questionaire given at screening
- •Other protocol defined criteria may apply
研究组 & 干预措施
BKM120 and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.
干预措施: Paclitaxel (Drug)
BKM120 and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.
干预措施: BKM120 (Drug)
Placebo and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.
干预措施: Paclitaxel (Drug)
Placebo and paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.
干预措施: BKM120 matching placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)
时间窗: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed
PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Overall Survival by Kaplan-Meier Estimate (Phase ll)(every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed)
- Overall Response Rate (Phase ll)(every 8 weeks after randomization Up to 3 months after end of Treatment)
- Duration of Response (Phase Lll)(every 8 weeks after randomization Up to 3 months after end of Treatment)
- Time to Response (Phase Lll)(every 8 weeks after randomization Up to 3 months after end of Treatment)
- Clinical Benefit Rate (CBR) (Phase ll)(every 8 weeks after randomization Up to 3 months after end of Treatment)
- Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll)(Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.)
- Time to Definitive Deterioration of ECOG Performance Status (Phase Lll)(every 4 weeks)