EMBER-2: A Phase 1, Open-Label, Preoperative Window Study Evaluating the Biological Effects of LY3484356 in Post-menopausal Women With Stage I-III Estrogen Receptor-Positive, HER2-Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 19
- 主要终点
- Percent Change From Baseline in Estrogen Receptor (ER) Expression
研究概览
简要总结
The purpose for this study is to see if the study drug, LY3484356, is safe and to determine what effects it has on breast cancer in participants with Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) early stage (stage I-III) breast cancer, when given prior to surgery. Participation in this study could last up to 2.5 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Have histologically confirmed invasive ER+, HER2- breast carcinoma
- •Be willing and able to provide pre- and on-treatment tumor samples
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale
- •Have adequate organ function
- •Be able to swallow capsules
- •Be a postmenopausal woman
排除标准
- •Have bilateral invasive breast cancer
- •Have metastatic breast cancer
- •Plan to receive concurrent neoadjuvant therapy with any other non-protocol anti-cancer therapy
- •Have had prior therapy (of any kind) for an invasive or non-invasive breast cancer
- •Have had prior radiotherapy to the ipsilateral chest wall for any malignancy
- •Have had prior anti-estrogen therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer
- •Have had prior hormone-replacement therapy within 4 weeks of the start of study treatment
- •Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s)
- •Have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled
- •Have another serious medical condition
- •Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
研究组 & 干预措施
200 milligrams (mg) LY3484356
Participants received 200 mg LY3484356 administered orally once daily for 15 days
干预措施: LY3484356 (Drug)
400 mg LY3484356
Participants received 400 mg LY3484356 administered orally once daily for 15 days
干预措施: LY3484356 (Drug)
800 mg LY3484356
Participants received 800 mg LY3484356 administered orally once daily for 15 days
干预措施: LY3484356 (Drug)
结局指标
主要结局
Percent Change From Baseline in Estrogen Receptor (ER) Expression
时间窗: Baseline, Day 15
Tumor tissue collected by biopsy is used to determine ER expression. ER expression is measured by immunohistochemistry (IHC) and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total ER H-score ranged from 0 to 300, where a higher score indicated stronger ER expression. Percent change in ER expression was defined as 100\*(ER expression on-treatment - ER expression pre-treatment)/(ER expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(ER expression on-treatment/ER expression pre-treatment).
次要结局
- Percent Change From Baseline in Ki-67(Baseline, Day 15)
- Percent Change From Baseline in Progesterone Receptor (PR) Expression(Baseline, Day 15)
- Pharmacokinetics (PK): Plasma Concentration of LY3484356(Day 1: 3.5 hours (h) postdose; Day 8: Predose; Day 8: 3.5 h postdose)