A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 432
- 试验地点
- 38
- 主要终点
- Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)
研究概览
简要总结
This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment.
Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).
详细描述
Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BKM120 100mg + Fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
干预措施: Fulvestrant (Drug)
BKM120 100mg + Fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
干预措施: BKM120 (Drug)
Placebo + Fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
干预措施: Fulvestrant (Drug)
Placebo + Fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
干预措施: BKM120 matching placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)
时间窗: Every 6 weeks after randomization up to a maximum of 4 years
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization.
次要结局
- Progression Free Survival (PFS) by PIK3CA Mutational Status(Every 6 weeks after randomization up to a maximum of 5 years)
- Overall Response Rate (ORR) by PIK3CA Mutational Status(Every 6 weeks after randomization up to a maximum of 5 years)
- Clinical Benefit Rate (CBR) by PIK3CA Mutational Status(Week 14, Week 24)
- Overall Survival (OS) - Full Analysis Set (FAS)(Every 6 weeks after randomization up to a maximum of 5 years)
- Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS)(From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years)
- Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS)(Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.)
- Overall Survival (OS) by PIK3CA Mutational Status(Every 6 weeks after randomization up to a maximum of 5 years)
- Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)(C1D15, C2D1, C3D1 and C4D1)
- Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS)(C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose)
- Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)(Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit)