Molecularly Stratified Parallel Cohort, Single Arm Phase II Trial of the Phosphoinositide 3-kinase (PI3K) Inhibitor Buparlisib (BKM120) in Combination With Tamoxifen in Patients With Hormone Receptor-positive, HER2-negative Inoperable (Locally Advanced or Metastatic) Breast Cancer With Prior Exposure to Antihormonal Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Progression free survival (PFS)-rate in the full population, after 6 months
研究概览
简要总结
This is a clinical trial with a molecularly stratified parallel cohort, single arm design to explore the efficacy and safety of BKM120 in combination with tamoxifen in patients with ER/PR-positive, HER2-negative breast cancer with prior exposure to antihormonal therapy, and different biomarker profiles, two of them potentially indicative of constitutive PI3K pathway activation.
详细描述
This is a clinical trial with a molecularly stratified parallel cohort, single arm design to explore the efficacy and safety of BKM120 in combination with tamoxifen in patients with ER/PR-positive, HER2-negative breast cancer with prior exposure to antihormonal therapy, and different biomarker profiles, two of them potentially indicative of constitutive PI3K pathway activation:
- PIK3CA mutation/preserved PTEN expression
- PIK3CA wildtype or mutation/ loss of PTEN expression
- PIK3CA wildtype/preserved PTEN expression. This trial will explore, if the combination of BKM120 and tamoxifen can overcome resistance to antihormonal therapies. BKM120 is selective for class I PI3K enzymes with no mTOR inhibitory activity that has entered Phase II and III clinical trials. The tumor suppressor PTEN is the most important negative regulator of the PI3K signaling pathway. Therefore, in addition the trial will prospectively evaluate PIK3CA mutations and/or loss of PTEN expression as predictive biomarkers for clinical benefit from combined treatment with BKM120 and tamoxifen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
- •Patient has radiologic or objective evidence of inoperable locally advanced, or metastatic breast cancer
- •Patient has a known hormone receptor status HR-positive (ER and/or PR positive) and HER2-negative status
- •Patient has a representative archival formalin-fixed tumor biopsy (metastasis or primary tumor)
- •Patient has prior exposure to antihormonal therapy
- •Patient has received ≤ 2 prior antihormonal treatments in the metastatic setting
- •Prior treatment with tamoxifen in the (neo-)adjuvant setting is allowed but has to be discontinued for at least 1 year.
- •Patient may have received up to one prior chemotherapy in the metastatic setting
- •Measurable or non-measurable lesions according to RECIST v1.1 criteria
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2
排除标准
- •Patient has received previous treatment with a PI3K- or AKT-inhibitor or mTOR-inhibitors
- •Prior treatment with Tamoxifen in the metastatic setting. Treatment with tamoxifen in the (neo-)adjuvant setting is allowed, but has to be discontinued for at least 1 year
- •Patient has symptomatic CNS metastases
- •Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM-IV).
- •Patient has a known history of HIV infection (testing not mandatory) infection
研究组 & 干预措施
BKM120 + Tamoxifen
BKM120 (Buparlisib): 100 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle
Tamoxifen: 20 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle
干预措施: BKM120 (Drug)
BKM120 + Tamoxifen
BKM120 (Buparlisib): 100 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle
Tamoxifen: 20 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle
干预措施: Tamoxifen (Drug)
结局指标
主要结局
Progression free survival (PFS)-rate in the full population, after 6 months
时间窗: 6 months
PFS is defined as time from date of start of treatment to the date of the event, defined as the first documented disease progression or death due to any cause per local investigator assessment
次要结局
- Progression free survival (PFS)- rate in the subpopulations after 6 months of combination therapy(6 months)
- Progression-free survival (PFS)(6 months)
- 1 year overall survival (OS) rate(1 year)
- 2 years overall survival (OS) rate(2 years)
- Overall response rate (ORR)(6 months)
- Disease control rate (DCR)(6 months)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(From date of informed consent to +30 days from last application of study medication)
- Incidence and severity of depressive episodes during the course of treatment(From date of informed consent to +30 days from last application of study medication)
研究者
Anja Welt
Principal Investigator
University Hospital, Essen