Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast Cancer Progressed to Anti-HER2 Based Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 27
- 主要终点
- MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant
研究概览
简要总结
The main purpose of this open-label, dose-escalation, phase Ib study is to identify the appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer
详细描述
This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to the post-menopausal patients with hormone-sensitive disease.
MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide 3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.
This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611 given in combination with Trastuzumab with/without Fulvestrant.
The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review Committee.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- 否
入选标准
- •Histologically confirmed invasive adenocarcinoma of the breast
- •Known HER2+ breast cancer
- •Advanced or metastatic breast cancer harbouring PIK3CA mutation on tissue sample
- •> 2 lines of anti-HER2 based regimens with at least 1 regimen with trastuzumab
- •Radiological documented evidence of progressive disease
- •Life expectancy ≥ 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
排除标准
- •Previous treatment with PI3K inhibitors
- •Brain metastases untreated, unless treated > 4 weeks and only if clinically stable and not receiving corticosteroids
- •History of clinically significant bowel disease
- •≥ grade 2 diarrhoea
- •History of significant, uncontrolled, or active cardiovascular disease
- •Any serious and/or unstable pre-existing psychiatric or neurologic illness or other conditions that could interfere with patient's safety
- •Not controlled diabetes mellitus (glycated haemoglobin [HbA1c] >7%) and fasting plasma glucose >126 mg/dL
- •Concurrent chronic treatment with steroids, as immunosuppressant, or another immunosuppressive agent
研究组 & 干预措施
MEN1611
MEN1611 + Trastuzumab +/- Fulvestrant
干预措施: MEN1611 (Drug)
MEN1611
MEN1611 + Trastuzumab +/- Fulvestrant
干预措施: Trastuzumab (Drug)
MEN1611
MEN1611 + Trastuzumab +/- Fulvestrant
干预措施: Fulvestrant (Drug)
结局指标
主要结局
MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant
时间窗: Up to 28 Days
MTD was defined as the highest dose level at which no more than 1 participant experienced a DLT during the 28-day DLT assessment window.
Number of Participants With DLTs of MEN1611 in Combination With Trastuzumab ± Fulvestrant
时间窗: Up to 28 days
DLT was defined as the occurrence of any of the protocol defined adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during 28 days after the first MEN1611 administration.
RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant
时间窗: Up to 28 days
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant experienced a DLT during the DLT assessment window (28days), or the maximum dose judged to be tolerable.
次要结局
- Best Overall Response (BOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)
- Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)
- Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)
- Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)
- Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)
- Overall Survival (OS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant(Up to 3 years)