Back to resultsCardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Primary Purpose
Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Entinostat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring entinostat, solid tumor, Histone Deacetylase Inhibitors
Eligibility Criteria
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
Sites / Locations
- The START Center for Cancer Care
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Entinostat
Placebo
Arm Description
Participants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions.
Participants received a single dose of placebo-matching entinostat under fasted conditions.
Outcomes
Primary Outcome Measures
Change from Baseline in Heart Rate (HR)
Heart rate measured in beats per minute (bpm).
Change from Baseline in Electrocardiogram Procedures
Change from baseline in QT interval corrected for heart rate (Qtc), PR interval (PR) and QRS complex (QRS).
Change from Baseline in T-Cell Morphology
Secondary Outcome Measures
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.
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.
Change from Baseline in Vital Signs
Vital signs included temperature, pulse, blood pressure, and respiration rate
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
Change from Baseline in QTc
Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
Tmax (Time of Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
AUC0-24 (Area under the Plasma Concentration-time Curve from Time Zero to 24 hours) of Entinostat when given as a Single Supratherapeutic Dose
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
AUC0-inf (Area under the Plasma Concentration-time Curve from 0-time Extrapolated to Infinity) of Entinostat when given as a Single Supratherapeutic Dose
t1/2 (Elimination Half-life and Apparent Plasma Terminal Phase Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02897778
Brief Title
Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Official Title
A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 24, 2016 (Actual)
Primary Completion Date
March 13, 2017 (Actual)
Study Completion Date
March 13, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syndax Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Digestive System Neoplasms, Endocrine Gland Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Diseases, Breast Neoplasms, Breast Diseases, Renal Neoplasm, Solid Tumors
Keywords
entinostat, solid tumor, Histone Deacetylase Inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Entinostat
Arm Type
Active Comparator
Arm Description
Participants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received a single dose of placebo-matching entinostat under fasted conditions.
Intervention Type
Drug
Intervention Name(s)
Entinostat
Other Intervention Name(s)
SNDX-275, MS-275
Intervention Description
Single, supratherapeutic dose of entinostat given orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single dose of placebo-matching entinostat (containing inactive ingredients matching the appearance of the active product).
Primary Outcome Measure Information:
Title
Change from Baseline in Heart Rate (HR)
Description
Heart rate measured in beats per minute (bpm).
Time Frame
Baseline (pre-dose) through 24 hours post-dose
Title
Change from Baseline in Electrocardiogram Procedures
Description
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
Title
Change from Baseline in T-Cell Morphology
Time Frame
Baseline (pre-dose) through 24 hours post-dose
Secondary Outcome Measure Information:
Title
Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)
Description
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)
Title
Number of Participants with Clinically Significant Abnormalities in Laboratory Values Reported as a TEAE
Description
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)
Title
Change from Baseline in Vital Signs
Description
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)
Title
Change from Baseline in ECG Values
Description
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)
Title
Change from Baseline in QTc
Time Frame
Pre-dose through 24 hours post-dose
Title
Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
Tmax (Time of Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
AUC0-24 (Area under the Plasma Concentration-time Curve from Time Zero to 24 hours) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
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
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
AUC0-inf (Area under the Plasma Concentration-time Curve from 0-time Extrapolated to Infinity) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
t1/2 (Elimination Half-life and Apparent Plasma Terminal Phase Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Title
λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
Time Frame
Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Other Pre-specified Outcome Measures:
Title
Changes in Immune Regulatory Cells after a Single Dose of Entinostat, when given at a Supratherapeutic Dose, Relative to Placebo Control
Time Frame
Pre-dose through 14 days post-dose
Title
Variability and Changes in Protein Lysine Acetylation in Peripheral Blood Cells after a Single Dose of Entinostat, when given at a Supratherapeutic Dose and Examine the Underlying Biological Variation
Time Frame
Pre-dose through 14 days post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Meyers, MD, PhD
Organizational Affiliation
Syndax Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
The START Center for Cancer Care
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Data will be reviewed throughout the study by the sponsor, Contract Research Organization (CRO) assisting with Serious Adverse Event (SAE) management, and routine monitoring to safeguard the interests of trial patients and to assess the safety of the interventions administered during the trial.
Learn more about this trial
Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
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