A Phase IIa, Open-label Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Camizestrant in Combination With Atirmociclib in Participants With ER-positive, HER2-negative Advanced Breast Cancer (SERENA-1b)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 7
- 主要终点
- Number of participants with adverse events (AEs) and serious AEs
研究概览
简要总结
A study to investigate camizestrant in combination with atirmociclib in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.
详细描述
This is a Phase IIa, sequential assignment, non- randomized, open-label treatment study to determine the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of camizestrant in combination with atirmociclib.
The single-arm study includes:
- Screening period
- Atirmociclib single dose period
- Doublet intervention period
- Post-treatment follow-up period
研究设计
- 研究类型
- 干预性
- 分配方式
- 不适用
- 干预模型
- 单组
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
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
- Main Inclusion Criteria:
- Participants with advanced adenocarcinoma of the breast and must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease.
- Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting investigational medicinal products.
- Eastern cooperative oncology group (ECOG)/World Health Organization (WHO) performance status 0 to 1, and a minimum life expectancy of 12 weeks.
- At least one lesion that is measurable and/or non-measurable, as per RECIST 1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray, or clinical examination.
- Menopausal status
- Pre-menopausal women must start GnRH agonist therapy at least 4 weeks before study treatment and continue throughout the study.
- Post-menopausal women must meet one of these criteria: bilateral oophorectomy, age ≥60 years, age ≥50 years with ≥12 months amenorrhea and intact uterus without hormonal therapy, or age <60 years with ≥12 months amenorrhea and post-menopausal hormone levels.
- Histological or cytological confirmation of adenocarcinoma of the breast.
- Participants of childbearing potential must agree to use one highly effective contraceptive measure.
- Documentation of ER-positive tumor irrespective of progesterone receptor status.
- Main
排除标准
- A participant who has received 2 or more lines of CDK4/6 inhibitors in the advanced disease setting.
- A participant who has received prior camizestrant or atirmociclib treatment in the advanced disease setting.
- Patients previously treated with other next generation selective estrogen receptor degrader (SERDs) or other experimental ETs in the advanced disease setting.
- Patients previously treated with other experimental cyclin-dependent kinase (CDK) inhibitors are not eligible.
- Inability to swallow oral medications.
- Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia).
- Presence of life-threatening metastatic visceral disease.
- Any evidence of severe or uncontrolled systemic diseases.
- Contraindication to or known intolerance/hypersensitivity of/to camizestrant or atirmociclib.
研究组 & 干预措施
Camizestrant + Atirmociclib
Participants will receive a single dose of atirmociclib on Day -1 followed by combination of camizestrant and atirmociclib from Day 1.
干预措施: Camizestrant (Drug)
Camizestrant + Atirmociclib
Participants will receive a single dose of atirmociclib on Day -1 followed by combination of camizestrant and atirmociclib from Day 1.
干预措施: Atirmociclib (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs) and serious AEs
时间窗: Up to Post-Treatment Follow up (Day 30 Post Dose)
To investigate the safety and tolerability of camizestrant in combination with atirmociclib.
次要结局
- Maximum concentration observed (Cmax)(At pre-defined intervals from Day -1 to Day 57)
- Area under plasma concentration-time curve from time 0 to infinity (AUCinf)(At pre-defined intervals from Day -1 to Day 57)
- Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)(At pre-defined intervals from Day -1 to Day 57)
- Time to reach maximum (peak) plasma concentration following drug administration (tmax)(At pre-defined intervals from Day -1 to Day 57)
- Terminal elimination rate constant (λz)(At pre-defined intervals from Day -1 to Day 57)
- Terminal elimination half-life (t½λz)(At pre-defined intervals from Day -1 to Day 57)
- Apparent total body clearance (CL/F)(At pre-defined intervals from Day -1 to Day 57)
- Apparent volume of distribution at steady state (Vss/F)(At pre-defined intervals from Day -1 to Day 57)
- Apparent volume of distribution based on the terminal phase (Vz/F)(At pre-defined intervals from Day -1 to Day 57)
- Maximum concentration observed at steady state (Cssmax)(At pre-defined intervals from Day -1 to Day 57)
- Area under the curve from 0 to the end of dosing interval (AUC0-tau)(At pre-defined intervals from Day -1 to Day 57)
- Area under the curve from 0 to the end of dosing interval at steady state (AUCss0-tau)(At pre-defined intervals from Day -1 to Day 57)
- Time to reach maximum plasma concentration at steady state (tssmax)(At pre-defined intervals from Day -1 to Day 57)
- Objective Response Rate (ORR)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Clinical Benefit Rate at 24 Weeks (CBR24)(At 24 weeks)
- Percentage change in tumor size(Up to 2 years)
- Progression Free Survival (PFS)(Up to 2 years)
- Progression-free survival landmark 6 months (PFSLM6m)(At 6 months)
- Progression-free survival landmark 12 months (PFSLM12m)(At 12 months)
研究者
研究点 (7)
标识符
- NCT 编号
- NCT07427394
- 其他研究编号
- D853CC00001
日期
- 首次提交
- (7个月前)
- 首次发布
- (7个月前)
- 主要完成日期
- (明年)
- 研究完成日期
- (明年)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.