A Randomised, Open-Label, Parallel-Group, Pre-surgical Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2-negative Primary Breast Cancer (SERENA-3)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Percentage Change From Baseline in Estrogen Receptor (ER) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)
研究概览
简要总结
This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics (PK) of different doses of oral AZD9833 in post-menopausal women with primary breast cancer
详细描述
The study will be conducted in approximately 20 study centers across 3 countries and will be conducted in three stages (stage 1, stage 2 and stage 3). After the screening visit and confirmation of eligibility, evaluable participants will be enrolled across treatment groups. In stage 1, up to 24 evaluable participants across two treatment groups will be enrolled. A Safety and Data Monitoring Committee will convene to review stage 1 data and decide whether further treatment groups are required in stage 2. Stage 2 will include participants across up to 3 treatment groups. Stage 3 will include two treatment groups:
Stage 1 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily
Stage 2 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily Group 3: AZD9833 Dose C once daily
Stage 3 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily
Adverse events and concomitant medications information will be collected throughout the study. Thereafter there will be 28-day follow-up visit after discontinuation of study treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 130 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- •Intervention with any of the following:
- •Use of sex-hormone-containing drugs within 6 months prior to the first dose of study treatment
- •Medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5, sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index
- •Drugs that are known to prolong QT and have a known risk of torsades de pointes
- •Inflammatory breast cancer
- •Any evidence of severe or uncontrolled systemic diseases which in the investigator's opinion makes it undesirable for the participant to participate in the study
- •Any of the following cardiovascular criteria: Mean resting QTcF > 470 msec; resting heart rate of < 50 bpm for stages 1 and 2 at screening;resting heart rate <60 bpm at screening for Stage 3; any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; any factors that increase the risk of QTc prolongation or risk of arrhythmic events; known left ventricular ejection fraction < 50%; significant cardiovascular procedure or event within the last 6 months; uncontrolled hypertension or symptomatic hypotension
- •Inadequate bone marrow reserve or organ function
- •Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833
- •History of hypersensitivity to active or inactive excipients of AZD9833
- •Previous randomisation in the present study
- •Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements
研究组 & 干预措施
Stage 1: AZD9833 Dose A
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.
干预措施: AZD9833 (Drug)
Stage 1: AZD9833 Dose B
Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.
干预措施: AZD9833 (Drug)
Stage 2: AZD9833 Dose A
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study.
干预措施: AZD9833 (Drug)
Stage 2: AZD9833 Dose B
Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study.
干预措施: AZD9833 (Drug)
Stage 2: AZD9833 Dose C
Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.
干预措施: AZD9833 (Drug)
Stage 3: AZD9833 Dose A
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study.
干预措施: AZD9833 (Drug)
Stage 3: AZD9833: Dose B
Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 3 of the study.
干预措施: AZD9833 (Drug)
结局指标
主要结局
Percentage Change From Baseline in Estrogen Receptor (ER) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)
时间窗: Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
The pharmacodynamic (PD) effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by immunohistochemistry (IHC) method. The percentage change was calculated from an analysis of covariance (ANCVOA) model adjusting for baseline ER score and day of on-treatment biopsy.
Percentage Change From Baseline in ER Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)
时间窗: Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
The PD effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline ER H-score \< 10. The percentage change was calculated from ANCVOA model adjusting for baseline ER score and day of on-treatment biopsy.
次要结局
- Percentage Change From Baseline in Progesterone Receptor (PgR) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)(Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3]))
- Percentage Change From Baseline in PgR Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)(Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3]))
- Number of Patients With Adverse Events (AEs)(From screening (Day -21 to 1) through 28-day follow-up (Upto 2 months))
- Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Primary Analysis)(Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3]))
- Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)(Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3]))
- Plasma Concentrations of AZD9833(Days 5-7 or Days 12-15 (Pre and Post biopsy))