GCC 0927 A Pilot and Phase II Study of Entinostat and Anastrozole/Tamoxifen in Women With Triple Negative Breast Cancer to Evaluate Biomarkers and Surrogates for Response
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This phase II trial is studying how well giving entinostat and anastrozole together works in treating postmenopausal women with triple-negative breast cancer that can be removed by surgery. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving entinostat together with anastrozole may be an effective treatment for breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of entinostat in combination with anastrozole or tamoxifen. (Pilot) II. To determine the optimal dose of entinostat in combination with anastrozole or tamoxifen for phase II. (Pilot) III. To determine baseline and percentage change in proliferative index (Ki67) before and after treatment with entinostat and anastrozole/tamoxifen in triple negative breast cancer (TNBC). (Phase II) IV. To determine the estrogen receptor (ER) expression after treatment with entinostat and anastrozole/tamoxifen in TNBC. (Phase II)
SECONDARY OBJECTIVES:
I. To evaluate baseline and change in the expression levels of progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and aromatase before and after treatment with entinostat and anastrozole/tamoxifen.
II. To assess baseline and change in tumor tissue histone H3 and H4 acetylation before and after treatment with entinostat and anastrozole/tamoxifen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
no masking
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
entinostat & anastrozole neoadjuvant
Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery.
Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
干预措施: entinostat (Drug)
entinostat & anastrozole neoadjuvant
Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery.
Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
干预措施: anastrozole (Drug)
entinostat & anastrozole neoadjuvant
Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery.
Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
干预措施: diagnostic laboratory biomarker analysis (Other)
entinostat & anastrozole neoadjuvant
Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery.
Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
干预措施: therapeutic conventional surgery (Procedure)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Participants were followed during the study and for 30 days post treatment, up to 59 days
To address the safety of the regimen, a maximum width 90% confidence interval for any grade 3 or higher toxicity will be approximately 30%. For 5 patients in this study, if the true unknown probability of a rare toxicity is 10%, the probability of observing 1 or more toxicities is 97%, and if the true toxicity rate is 5% then the probability of observing one or more rare toxicities is 83%.
Recommended Phase II Dose of Entinostat in Combination With Anastrozole (Pilot)
时间窗: Duration of the study is 29 days followed by 30 days end of study assessment visit, up to 59 days
Since the study was terminated early there was insufficient data for analysis and to recommend a phase II dose of entinostat in combination with anastrozole
Change in Proliferative Index (Ki67) (Phase II)
时间窗: Baseline to the time of surgery, within 6 days after the last dose of entinostat, up to 35 days
The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.
Change in Estrogen-receptor (ER) Expression (Phase II)
时间窗: Baseline before the study treatment and at the time of surgery, up to 30 days
The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.
次要结局
- The Pathological Response to Entinostat and Anastrozole(Pathological response was assessed after the surgery, up to 59 days)
- Clinical Response to Entinostat and Anastrozole(Clinical response was assessed during the study treatment and before the surgery, up to 29 days)
- Change in HER2(Baseline before study treatment and at the time of surgery, up to 30 days)