A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change from Baseline in T-Cell Morphology
研究概览
简要总结
The purpose of this study is to evaluate the effect of entinostat on heart rate and other electrocardiogram (ECG) parameters. This study will also evaluate the safety and tolerability of entinostat, as well as pharmacokinetic and pharmacodynamic parameters.
详细描述
This is a single center, randomized, placebo-controlled, single dosing schedule, double-blinded study to evaluate the effect of entinostat as compared to placebo on the electrical activity of the heart in patients with advanced solid tumors. Thirty patients will be randomized in a 1:1 ratio to receive either entinostat or placebo. Study treatment will be blinded to patients and the Investigator. ECG analysts will be blinded to the patient, visit, and treatment allocation. Patients will be on study up to 30 days following study drug administration. Total study duration is expected to be 9 months. After completing this study and at the discretion of the Investigator, patients may elect to enroll into a separate continuation study (SNDX-275-0141).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is not responsive to standard therapy(ies) or for which there is no approved therapy
- •Patients must have acceptable laboratory requirements
- •Left ventricular ejection fraction as measured by echocardiogram or multiple-gated acquisition scan that is above the institutional lower level of normal or greater than 50%
- •Has experienced resolution of toxic effect(s) of the most recent prior chemotherapy and/or prior surgical and radiation treatment
- •Must be able to understand and give written informed consent and comply with study procedures
排除标准
- •If the patient has brain metastasis, they must have stable neurologic status without the use of steroids or on a stable or decreasing dose of steroids
- •Presence of clinically significant gastrointestinal abnormalities that may affect the absorption of study treatments
- •A medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the Investigator
- •Patient has a concomitant cardiovascular issue that precludes adequate study treatment compliance or increases patient risk
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study
- •Prior anti-cancer monoclonal antibody within 4 weeks prior to baseline
- •Currently enrolled in another investigational study
- •Has disease that is suitable for approved therapy administered with curative intent
研究组 & 干预措施
Entinostat
Participants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions.
干预措施: Entinostat (Drug)
Placebo
Participants received a single dose of placebo-matching entinostat under fasted conditions.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline in T-Cell Morphology
时间窗: Baseline (pre-dose) through 24 hours post-dose
Change from Baseline in Electrocardiogram Procedures
时间窗: Baseline (pre-dose) through 24 hours post-dose
Change from baseline in QT interval corrected for heart rate (Qtc), PR interval (PR) and QRS complex (QRS).
Change from Baseline in Heart Rate (HR)
时间窗: Baseline (pre-dose) through 24 hours post-dose
Heart rate measured in beats per minute (bpm).
次要结局
- AUC0-t (Area under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- Change from Baseline in Vital Signs(Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable))
- Tmax (Time of Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- Change from Baseline in ECG Values(Baseline ()pre-dose through 14 days post-dose or 30 day safety follow-up visit (if applicable))
- Change from Baseline in QTc(Pre-dose through 24 hours post-dose)
- Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- AUC0-inf (Area under the Plasma Concentration-time Curve from 0-time Extrapolated to Infinity) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)(First dose through 30 days post-dose or through resolution of acute toxicities (Up to 31 days))
- Number of Participants with Clinically Significant Abnormalities in Laboratory Values Reported as a TEAE(Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable))
- AUC0-24 (Area under the Plasma Concentration-time Curve from Time Zero to 24 hours) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)
- t1/2 (Elimination Half-life and Apparent Plasma Terminal Phase Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose(Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose)