A Pilot Study Evaluating Surrogates of Response to Short Term Oral Suberoylanilide Hydroxamic Acid (SAHA) in Women With Newly Diagnosed Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Change in Tissue Proliferation After 3 Days of Treatment
研究概览
简要总结
This phase II trial is studying how well vorinostat works in treating women who are undergoing surgery for newly diagnosed stage I, stage II, or stage III breast cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may shrink the tumor so that it can be removed.
详细描述
PRIMARY OBJECTIVE:
I. Determine the safety and tolerability of vorinostat in women undergoing conventional surgery for newly diagnosed stage I-III breast cancer.
OULINE: This is a multicenter, pilot study.
Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo surgical resection of the tumor on day 0.
After completion of study treatment, patients are followed for 30 days.
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
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
- •No prior or concurrent hormonal therapy for breast cancer
- •Histologically confirmed breast cancer, stage I-III disease, scheduled to undergo definitive surgery or other primary treatment (e.g., preoperative/neoadjuvant systemic treatment) for breast cancer
- •ECOG 0-2 OR Karnofsky 60-100%
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal
- •PT ≤ 14 seconds
- •Creatinine normal
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled intercurrent illness
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to vorinostat
- •At least 30 days since prior hormone replacement therapy (e.g., estrogen and/or progestin)
- •Concurrent vaginal hormone preparations (e.g., vagifem or estring) allowed
- •No concurrent birth control pills
- •No prior radiotherapy to the ipsilateral breast
- •No prior or concurrent radiotherapy for breast cancer
- •No prior or concurrent novel therapy for breast cancer
- •At least 14 days since prior valproic acid or another histone deacetylase inhibitor
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent therapy for this cancer
- •WBC ≥ 3,000/mm^3
- •Exclusion criteria:
- •Patients must not be recieving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA.
- •Patients may not be taking valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to initiating SAHA.
- •Women who are pregnant.
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo conventional surgery of the tumor on day 0. After completion of study treatment, patients are followed for 30 days.
干预措施: vorinostat (Drug)
Arm I
Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo conventional surgery of the tumor on day 0. After completion of study treatment, patients are followed for 30 days.
干预措施: conventional surgery (Other)
结局指标
主要结局
Change in Tissue Proliferation After 3 Days of Treatment
时间窗: After 3 days of vorinostat
Change in Ki-67 (a marker of tissue proliferation) by IHC compared to baseline in the treated (22 evaluable samples) or untreated patients (15 evaluable samples) were analyzed between groups. Ki-67 is a protein in cells that increases as cellsprepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells.
Change in Tissue Apoptosis After 3 Days of Treatment
时间窗: Baseline and after 3 day of vorinostat
Change in cleaved caspase-3 (a marker of tissue apoptosis) by IHC compared to baseline in the treated (19 evaluable samples) or untreated patients (12 evaluable samples) were analyzed between groups. Cleaved caspase-3 is a protein in cells involved in apoptosis (cell death).
Number of Participants With Adverse Events
时间窗: After 3 days of vorinostat
Participants were evaluated for adverse events due to vorinostat to assess if it was safe to give the drug prior to surgery. 17 of 25 participants who received vorinostat experienced at least 1 adverse event believed to be related to the study drug; no adverse events were severe, and the treatment was considered safe.
次要结局
- Change in Tissue Histone Acetylation After 3 Days of Treatment(Baseline and after 3 day of Vorinostat)
- Change in Blood (Peripheral Blood Mononuclear Cells) Histone Acetylation After 3 Days of Treatment(Baseline and after 3 day of Vorinostat)