A Phase II Open-label, 2-Part, Multi-center Study of BYL719 (Alpelisib) in Combination With Fulvestrant for Men and Postmenopausal Women With PIK3CA Mutation Hormone Receptor (HR) Positive, HER2-negative, Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment in Japan
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 16
- 主要终点
- [Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.
详细描述
This is a Phase II open-label, 2-Part, multi-center study in Japan. The study will be conducted in two parts: Part 1 (Cohort 1) includes participants regardless of prior CDK4/6 inhibitor use and is designed to determine the recommended dose (RD), evaluate the tolerability and safety of alpelisib in combination with fulvestrant. Part 2 consists of 2 cohorts (the CDK4/6 inhibitor naive participants are in Cohort 2 and the CDK4/6 inhibitor pre-treated participants are in Cohort 3) which are designed to assess the efficacy and safety of alpelisib in combination with fulvestrant, will start once the RD of alpelisib is established.
Participants will be treated until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese man or postmenopausal woman
- •Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory.
- •Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
- •Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory
- •Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH or SISH) test is required by local laboratory testing
- •Participant has measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
- •Participant has advanced breast cancer
- •Participant has ECOG performance status 0 or 1
排除标准
- •Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
- •Participant has received prior treatment;
- •with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor for Cohort 1 and 3
- •with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, AKT inhibitor or CDK 4/6 inhibitor for Cohort 2
- •Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
- •Participant with inflammatory breast cancer at screening
- •Participant is concurrently using other anti-cancer therapy
- •Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
- •Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II (based on FPG and HbA1c)
- •Participant has currently documented pneumonitis /interstitial lung disease
- •History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
- •Participant with unresolved osteonecrosis of the jaw
- •Participant has a history of severe cutaneous reactions
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)
Participants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Alpelisib (Drug)
Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)
Participants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Fulvestrant (Drug)
Cohort 2: CDK4/6 inhibitor naive (Part 2)
Participants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Alpelisib (Drug)
Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)
Participants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Alpelisib (Drug)
Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)
Participants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Fulvestrant (Drug)
Cohort 2: CDK4/6 inhibitor naive (Part 2)
Participants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
干预措施: Fulvestrant (Drug)
结局指标
主要结局
[Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant
时间窗: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)
A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 2 cycles (the first 56 days) of treatment with alpelisib in combination with fulvestrant and meets any of the criteria specified in the protocol .
[Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants
时间窗: Up to approximately 36 months
ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.
次要结局
- [Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 37 months)
- [Part 2] Number of participants with dose adjustments(Up to approximately 37 months)
- [Part 2] Dose intensity for alpelisib and fulvestrant(Up to approximately 37 months)
- [Part 2] Duration of exposure for alpelisib and fulvestrant(Up to approximately 37 months)
- [Part 2] Plasma concentrations of alpelisib in combination with fulvestrant(Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days))
- [Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 37 months)
- [Part 1] Plasma concentrations of alpelisib in combination with fulvestrant(Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days))
- [Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants(Up to approximately 36 months)
- [Part 2] Progression Free Survival (PFS)(Up to approximately 36 months)
- [Part 2] Overall Survival (OS)(Up to approximately 60 months)
- [Part 2] Clinical Benefit Rate (CBR)(Up to approximately 36 months)
- [Part 2] Duration of Response (DOR)(Up to approximately 36 months)
- [Part 2] Time to Response (TTR)(Up to approximately 36 months)
- [Part 1] Number of participants with dose adjustments(Up to approximately 37 months)
- [Part 1] Dose intensity for alpelisib and fulvestrant(Up to approximately 37 months)
- [Part 1] Duration of exposure for alpelisib and fulvestrant(Up to approximately 37 months)
- [Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status(Up to approximately 36 months)