Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Change in Ki67 Cell Percentage
研究概览
简要总结
The purpose of this study is to microscopically examine breast cancer cells of pre-menopausal and post-menopausal women before and after exposure to one of the two commonly used breast cancer drugs, tamoxifen or fulvestrant.
详细描述
The researchers hypothesize that the cyclinD1-interactome can be used to orient the use of fulvestrant in premenopausal and postmenopausal women. To test this hypothesis, the researchers propose a pre-surgical randomized clinical trial of tamoxifen vs fulvestrant in the window between breast cancer diagnosis on core biopsy and definitive surgery. Women with ER/cyclinD1 positive tumors will be eligible. Response to tamoxifen or fulvestrant will be evaluated using standard proliferation index as well as gene expression signatures obtained in pre-clinical models of tamoxifen resistance and sensitivity to fulvestrant. In addition, the researchers propose to use cutting edge new technology allowing ex-vivo expansion of primary culture from only a few cancer cells obtained by fine needle biopsy. The researchers propose to compare the response of these primary cells to patient response. If successful, the impact of this work can support the expansion of use of fulvestrant to not only postmenopausal women but premenopausal women as well. In addition, it may serve as a proof of principle to maximize the use of biopsy material to predict treatment response
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the study treatment regimen and follow-up, must be obtained and documented according to the local regulatory requirements
- •Adult women greater than 18 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- •New diagnosis of invasive cyclin D1 +, ER+, PR +/-, Her2- breast cancer
- •Cyclin D1 positive as defined as a total immunohistochemical score of 5 or greater
- •Hormone receptor positive as defined as ≥ 10% positive stained cells
- •HER2-normal (IHC score 0-1 or FISH negative [in-situ hybridization (ISH) ratio <= 2.0 status])
- •Tumor size at least 5 mm with planned primary surgery at Mount Sinai
- •A negative urine dipstick pregnancy test
排除标准
- •Estrogen receptor negative invasive breast carcinoma as defined as less than 10% stained cells
- •Prior antiestrogen therapy
- •Tumor size less than 5 mm
- •Prior diagnosis of thrombosis or known hypercoagulable state
- •Known history of bleeding diathesis
- •Known liver disease
- •Prior treatment with neoadjuvant therapy
- •Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema).
- •Current severe or uncontrolled systemic disease
- •Pregnancy or lactation period. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices) during study treatment.
- •Prior malignancy (including invasive or ductal in-situ breast cancer) within 5 years prior to randomization, except curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.
研究组 & 干预措施
Fulvestrant
750 mg injection in 3 divided doses
干预措施: Fulvestrant (Drug)
Tamoxifen
20mg orally
干预措施: Tamoxifen (Drug)
结局指标
主要结局
Change in Ki67 Cell Percentage
时间窗: baseline and 2 weeks
The change in proliferation index as measured by the percentage of cells staining for Ki67 at 2 weeks as compared on baseline.
次要结局
- Change in Estrogen Receptor Level(baseline and 2 weeks)
- Incidence of Tamoxifen-resistance Gene Expression(2 weeks)
- Percentage of Cells Staining Positive Within the Breast Tumor(2 weeks)
- Change in Progesterone Receptor Level(baseline and 2 weeks)
- Drug Dose Level(2 weeks)
- Incidence of Fulvestrant-sensitivity Gene Expression(2 weeks)
研究者
Amy Tiersten
Professor
Icahn School of Medicine at Mount Sinai