Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors

Syndax Pharmaceuticals30 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Neoplasms Neoplasms, Glandular and Epithelial

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

Change from Baseline in Heart Rate (HR)

Heart rate measured in beats per minute (bpm).

Time frame: Baseline (pre-dose) through 24 hours post-dose

Change from Baseline in Electrocardiogram Procedures

Change from baseline in QT interval corrected for heart rate (Qtc), PR interval (PR) and QRS complex (QRS).

Time frame: Baseline (pre-dose) through 24 hours post-dose

Change from Baseline in T-Cell Morphology

Time frame: Baseline (pre-dose) through 24 hours post-dose

Secondary Outcomes

Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is an AE that occurs after the first dose of study drug. A SAE is defined as any AE that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage.

Time frame: 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

Standard safety laboratory tests included Chemistry, Hematology. Any hematologic or clinical chemistry abnormality considered by the investigator to be clinically significant was reported as a TEAE.

Time frame: Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable)

Change from Baseline in Vital Signs

Vital signs included temperature, pulse, blood pressure, and respiration rate

Time frame: Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable)

Change from Baseline in ECG Values

A 12-lead continuous ECG recording (via a Holter) was recorded on Day 1 for 25 hours. Safety ECGs were read and interpreted by the Investigator on-site for the purpose of safety monitoring and were transmitted electronically to the central ECG laboratory for clinical interpretation by a cardiologist

Time frame: Baseline ()pre-dose through 14 days post-dose or 30 day safety follow-up visit (if applicable)

Change from Baseline in QTc

Time frame: Pre-dose through 24 hours post-dose

Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose