A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,147
- 试验地点
- 62
- 主要终点
- Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
研究概览
简要总结
This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.
详细描述
Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).
Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).
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
- •Locally advanced or metastatic breast cancer
- •HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
- •Postmenopausal woman
- •A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
- •Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
- •Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1
- •Adequate bone marrow and organ function defined by laboratory values
排除标准
- •Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
- •More than one prior chemotherapy line for metastatic disease
- •Symptomatic brain metastases
- •Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- •Active heart (cardiac) disease as defined in the protocol
- •Certain scores on an anxiety and depression mood questionnaires
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: 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)
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)
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) in Full Population, Main Study Cohort and PI3K Unknown Cohort
时间窗: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to approximately 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.
次要结局
- Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths(From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years)
- Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1(Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.)
- Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)(Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.)
- Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)(Up to approx 27 months)
- Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30(Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment)
- Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort(Every 3 months following end of treatment visit, assessed for approximately 5 years)
- Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort(From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years)
- Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort(From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years)