A Pilot Clinical Trial to Evaluate the Biological Activity of HDAC (Histone Deacetylase Transferases) Inhibition on ER and PR Expression in Triple Negative Invasive Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Combined PR/ER response
研究概览
简要总结
This pilot clinical trial studies vorinostat before surgery in treating patients with triple-negative breast cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving enzyme inhibitor therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the ability of histone deacetylase (HDAC) inhibition using suberoylanilide hydroxamic acid (SAHA) (vorinostat) to induce expression of the estrogen receptor (ER) and progesterone receptor (PR) genes in solid human triple negative invasive breast cancer.
OUTLINE:
Patients receive vorinostat 400 mg daily orally (PO) on days 1-21 followed by surgery within 14 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
- •Resectable tumor measuring 2cm or more
- •Histologically documented, newly diagnosed, triple negative invasive breast cancer characterized by 0% immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for PR-alpha, and no amplification of human epidermal growth factor receptor 2 (HER2)/neu by fluorescent in situ hybridization (FISH) using institutional standard; standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and PR-beta
- •Southwest Oncology Group (SWOG) performance status of less than or equal to 1
- •Absolute neutrophil count (ANC) >= 1500/uL
- •Hemoglobin (Hgb) >= 9 g/dL
- •Platelets >= 100,000/uL
- •Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or =< 5.0 x ULN in patients with liver metastases
- •Creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 50 ml/min
- •Albumin >= 3 g/dL
- •Potassium >= lower limit normal (LLN)
- •Phosphorous >= LLN
- •Calcium >= LLN
- •Magnesium > LLN
- •Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment
- •Accessible for treatment and follow-up
- •Written informed consent prior to study entry
排除标准
- •HER2/neu amplification by FISH
- •Concurrent neoadjuvant anti-cancer treatment with chemotherapy, endocrine therapy, biologically targeted therapy or radiotherapy
- •Known hypersensitivity to SAHA
- •Preexisting hepatic impairment or renal impairment
- •Intent to receive additional neoadjuvant therapy prior to surgery
- •Concurrent use of an HDAC inhibitor or hydralazine
- •Known diagnosis of human immunodeficiency virus (HIV) infection
- •Major surgery < 4 weeks prior to starting study drug
- •Pregnant or breastfeeding or female of reproductive potential not using an effective method of birth control
- •Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
- •Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase inhibitors) within 6 months of study entry
- •Underlying medical, psychiatric or social conditions that would preclude patient from receiving treatment
研究组 & 干预措施
Treatment (vorinostat and surgery)
Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
干预措施: vorinostat (Drug)
Treatment (vorinostat and surgery)
Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
干预措施: therapeutic conventional surgery (Procedure)
Treatment (vorinostat and surgery)
Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Combined PR/ER response
时间窗: 21 days
The proportion of patients who achieve sufficient deacetylation of ER and PR will be estimable with a standard error no greater than +/- 0.05. The proportion of patients who exhibit a sufficient change in ER or PR expression can be estimated with similar precision. In addition, paired t-tests and McNamaraâs test will be used to evaluate whether the effect of vorinostat on deacetylation status or gene expression differs between ER or PR, and linear regression analysis will be used to evaluate the association between deacetylation changes and corresponding expression changes in ER and PR genes.
次要结局
- Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0(Within 3 days prior to surgery)