SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast): A Phase 2 Study on Fulvestrant Beyond Progression in Combination With Alpelisib for PIK3CA-mutated, Hormone-receptor Positive HER2 Negative Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 130
- 试验地点
- 25
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
The study is a nationwide, multicenter single-arm phase 2 study. The current phase 2 study investigates the efficacy of the combination of fulvestrant and alpelisib directly after progression on fulvestrant (either in first or second line, with or without previous use of CDK4/6-inhibitor) in patients with HR+ HER2- advanced breast cancer with PIK3CA mutated tumors.
All eligible patients must have progressive disease on fulvestrant as latest treatment line.
Previous treatment with a CDK4/6 inhibitor in first or second line is obligatory. After progressive disease is confirmed, it is important to continue fulvestrant (without CDK4/6 inhibition) during the screening period awaiting study enrollment.
After study enrollment all participants will be treated with alpelisib and fulvestrant beyond progression. Follow-up time will be until progression or death or until a different oncolytic treatment has started (in case no progressive disease during previous fulvestrant and alpelisib treatment has been documented).
Should participants discontinue due to reasons other than progression or death (e.g. toxicity), then they should still be evaluated for disease progression every 8 weeks as per protocol until progression, unless they do not wish to proceed with these screenings, or receive a different oncolytic treatment.
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
- All
- 接受健康志愿者
- 是
入选标准
- •Adult women and men (≥ 18 years of age) with proven diagnosis of adenocarcino-ma of the breast withlocoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent andfor whom chemotherapy is not clinically indicated
- •Estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancerbased on local la-boratory results. Tumor must be HER2- as defined by ASCO-CAP guidelines
- •Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy)
- •Previous treatment with a CDK4/6 inhibitor in the advanced setting
- •The presence of an activating PIK3CA mutation
- •Evaluable disease* as defined per RECIST v.1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
排除标准
- •Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in theshort term
- •Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningealdisease as indicated by clinical symptoms, cerebral edema, and/or progressive growth
- •Prior treatment with a PI3K /AKT/mTOR inhibitor
- •Type 1 diabetes or uncontrolled type 2 diabetes (Hba1C > 68 mmol/mol)
- •Clinically significant, uncontrolled heart disease and/or recent cardiac events
研究组 & 干预措施
Arm A (one-arm study)
Alpelisib plus fulvestrant beyond progression
干预措施: Alpelisib 150 MG Oral Tablet [Piqray] (Drug)
Arm A (one-arm study)
Alpelisib plus fulvestrant beyond progression
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: From registration to progression, assessed up to 36 months
Defined as time from study enrollment to disease progression or death from any cause, with censoring when fulvestrant and alpelisib are stopped and another treatment is initiated without confirmed disease progression.
次要结局
- Clinical Benefit Rate(From registration to progression, assessed up to 36 months)
- 'On treatment' Progression-free survival (PFS)(From registration to progression, assessed up to 36 months)
- Duration of Response (DoR)(From registration to progression, assessed up to 36 months)
- Objective Response Rate(From registration to progression, assessed up to 36 months)