Hydralazine as Demethylating Agent in Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- To explore the potency of a clinical tolerable dose of hydralazine as a demethylating agent as indicated.
研究概览
简要总结
This study will be conducted as a phase I/II clinical trial. In addition to determining the maximum tolerated dose (MTD) of hydralazine, the phase I trial will be performed to identify unexpected toxicities that may occur when hydralazine is used in conjunction with neoadjuvant chemotherapy in normotensive women with breast cancer. Once the phase I trial is successfully completed, the phase II trial to evaluate the efficacy of hydralazine in producing a demethylation effect will begin.
详细描述
The objective of this study is to determine the MTD for hydrazaline added to standard neoadjuvant chemotherapy for operable breast cancer. Four dose levels of hydrazalline are planned:
Dose Level 1: 150 mg/d 50 mg PO TID Dose Level 2: 200 mg/d 50 mg PO QID Dose Level 3: 225 mg/d 75 mg PO TID
Patients will be treated in cohorts of 3 and no patient may be treated at more that one dose level. Additional cohorts may not be initiated until toxicity has been fully evaluated in the current cohort of patients. The MTD is exceeded when a dose level produces a dose limiting toxicity (DLT) in at least two of the three patients in a cohort. Dose escalation will proceed by increasing the dose according to the following table.
Number of Events/Number in Cohort Action 0/3 Proceed to next dose level 1/3 Accrue 3 more patients at the same dose 1/3 + 0/3 Proceed to next dose level 1/3 + 1/3 Stop: Previous dose level is MTD 1/3 + 2/3 Stop: Previous dose level is MTD 1/3 + 3/3 Stop: Previous dose level is MTD 2/3 Stop: Previous dose level is MTD 3/3 Stop: Previous dose level is MTD
If the MTD has been exceeded by dose escalation and only one cohort with no observed toxicities was tested at the previous dose level, an additional cohort of 3 patients will be tested at the previous dose level. Thus, six patients must be treated at the dose declared the MTD. In the unlikely event that 150 mg/day of hydralazine, the starting dose, produces two or more DLTs, the daily dose of hydralazine will be reduced by 50mg to100 mg/day. If two or more toxicities are observed at this reduced dose level, the study will be stopped and the phase II study will not be performed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 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
- •Patients referred to the breast cancer service for diagnostic evaluation for "breast growth" will be candidates to participate in this study. Patients with history of elevated blood pressure and who are already on anti-hypertensives would be ideal candidates for this project. In such situation, hydralazine will replace other anti-hypertensives. There is no age limit for this study. Inclusion criteria are as follows:
- •Operable "invasive" breast cancer
- •Signed informed consent
- •Baseline blood pressure OFF antihypertensives > 110/60 mmHg
排除标准
- •Pre-existing hypotension
- •Pre-existing liver disease (liver function tests > 2x upper limits of normal ULM).
- •Pre-existing kidney (serum creatinine > 2 mg/dl).
- •Medical necessity to remain on beta-blockers that cannot be met by other agents.
研究组 & 干预措施
Hydralazine
The objective of this study is to determine the MTD for hydrazaline added to standard neoadjuvant chemotherapy for operable breast cancer. Four dose levels of hydrazalline are planned:
Dose Level 1: 150 mg/d 50 mg PO TID Dose Level 2: 200 mg/d 50 mg PO QID Dose Level 3: 225 mg/d 75 mg PO TID
干预措施: Hydralazine (Drug)
结局指标
主要结局
To explore the potency of a clinical tolerable dose of hydralazine as a demethylating agent as indicated.
次要结局
- 1. Reversal of promoter methylation of eight Tumor Suppressor Genes (TSGs) reported as candidates for epigenetic silencing in breast cancer using Methylation-Specific