An Open Label, Randomised, Pre-surgical, Pharmacodynamics Study to Compare the Biological Effects of AZD9496 Versus Fulvestrant in Postmenopausal Women With ER Positive HER-2 Negative Primary Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant
研究概览
简要总结
This is an open label randomised multicentre pre-surgical pharmacodynamics study to compare and assess the biological effects of AZD9496 and fulvestrant in postmenopausal women with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative (HER2-) primary breast cancer.
Patients will receive AZD9496 or fulvestrant and will have an on-treatment image
-guided core biopsy after 5-14 days of commencing treatment.
详细描述
This is an open label, randomized, multi-centre study in postmenopausal women with primary ER+ HER2- breast cancer. Patients will be randomised to an oral dose of 250 mg bd AZD9496 or 500mg fulvestrant i.m. administered on one occasion. Patients diagnosed with primary breast cancer who are scheduled for surgery with curative intent will be consented to the study including consent to use the formalin fixed paraffin embedded (FFPE) diagnostic tumor biopsy sample and fresh frozen tumor biopsy sample (if available) for research purposes. Patients may also consent to provide an optional pretreatment fresh frozen tumor biopsy sample if this was not obtained at the time of initial diagnostic biopsy. If the diagnostic biopsy was taken ≥ 6 weeks prior to starting treatment or was not of sufficient quality, new tumor core biopsies (FFPE and fresh frozen) must be taken. Following the screening visit, eligible patients will be randomised to receive one of the following study treatments:
- AZD9496 administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy OR
- fulvestrant 500 mg administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock.
After the morning dose of AZD9496 on the day of biopsy dosing will be stopped. If following initiation of AZD9496 treatment, dosing will be stopped if biopsy is postponed beyond Day 14. Patients will be considered not evaluable for the study if biopsy is postponed beyond day 14 of AZD9496/fulvestrant treatment initiation. Core tumor biopsies will be taken at either the time of definitive surgery or at a separate visit prior to surgery in the period between (and including) day 5 and day 14. Subjects who are scheduled to start a subsequent neoadjuvant therapy must have their core tumor biopsies performed before commencing neoadjuvant 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
盲法说明
Not applicable, thisis an open-label study.
入排标准
- 年龄范围
- 18 Years 至 120 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
- 未提供
研究组 & 干预措施
Standard arm
Fulvestrant, 500 mg
干预措施: Standard Arm - Fulvestrant (Drug)
AZD9496
250 mg bd taken orally for 5-14 days
干预措施: AZD9496 (Drug)
结局指标
主要结局
Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant
时间窗: Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression
次要结局
- Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant(Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment)
- Pharmacodynamics changes to Ki67 protein biomarker expression following treatment with AZD9496 or fulvestrant(Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment)
- Safety and tolerability of AZD9496(From first dose until 28 days after last dose of AZD9496)
- Safety and tolerability of fulvestrant(From first dose until 28 days after fulvestrant)
- Plasma concentration of AZD9496 - stand alone biopsy visit option(Blood samples collected close as possible to time of biopsy, 1-2 hours after biopsy and optional 3-4 hours after biopsy)
- Plasma concentration of fulvestrant(A blood sample will be collected anytime before biopsy.)
- Plasma concentration of AZD9496 - on the table biopsy option(Blood samples collected close as possible to time of biopsy, at least 2 hours after biopsy and 8-12 hours after last dose or at discharge which is defined as up to 12 hours after last dose)