A Phase II, Single Arm, Open-label Trial of Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) as Assessed by the Investigator
研究概览
简要总结
The purpose of this study is to determine if the triplet combination of dalpiciclib, fulvestrant, and pyrotinib is safe and effective in the treatment of hormone receptor-positive, HER2-low locally advanced/metastatic breast cancer following treatment with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib abemaciclib or ribociclib).
The study will employ a Bayesian Optimal Phase II (BOP2) design which explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs, and has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs.
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
- 否
入选标准
- •Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
- •Most recent tumor biopsy or surgical resection specimen must be either estrogen-receptor (ER) positive, progesterone receptors (PgR) positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines).
- •HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP guidelines).
- •Postmenopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin. Postmenopausal status is defined by any one of the following criteria:
- •Prior bilateral oophorectomy.
- •Age ≥60 years.
- •Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of anti-estrogen therapy.
- •Patient must have either measurable disease by RECIST 1.1 or only bone lesions in absence of measurable disease.
- •Eastern Cooperative Group (ECOG) performance status of 0 or
- •Previously treated on CDK 4/6 inhibitor(palbociclib, abemaciclib or ribociclib) with AI for at least 6 months
- •Adequate bone marrow and organ function.
排除标准
- •Patient with symptomatic visceral disease or any disease burden.
- •Patient has received more than one line of chemotherapy for advanced disease.
- •Previous treatment with Dalpiciclib /Pyrotinib /ADCe for advanced disease.
- •Progressed on more than one CDK 4/6 inhibitor
- •Patients with persistent symptoms and unstable brain metastases;
- •Any condition that makes the patient ineligible for endocrine therapy per the investigator's best judgment
研究组 & 干预措施
Dalpiciclib, Fulvestrant With Pyrotinib
Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg
干预措施: Dalpiciclib (Drug)
Dalpiciclib, Fulvestrant With Pyrotinib
Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg
干预措施: Pyrotinib (Drug)
Dalpiciclib, Fulvestrant With Pyrotinib
Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by the Investigator
时间窗: From start date to date of first documentation of progression or death (assessed up to 12 months)
Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
次要结局
- Overall Survival (OS)(From start date to date of death (assessed up to 24 months))
- Clinical Benefit Rate (CBR)(From start date to date of first documentation of progression or death (assessed up to 12 months))
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)(From the signing of the informed consent until 28 days after the last dose of study medication up to 14 months)
- Overall Response Rate (ORR)(From start date to date of first documentation of progression or death (assessed up to 12 months))