Clinical trial NCT02897778: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-09-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change from Baseline in Heart Rate (HR)
timeFrame: Baseline (pre-dose) through 24 hours post-dose
measure: Change from Baseline in Electrocardiogram Procedures
timeFrame: Baseline (pre-dose) through 24 hours post-dose
measure: Change from Baseline in T-Cell Morphology
timeFrame: Baseline (pre-dose) through 24 hours post-dose
Secondary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)
timeFrame: First dose through 30 days post-dose or through resolution of acute toxicities (Up to 31 days)
measure: Number of Participants with Clinically Significant Abnormalities in Laboratory Values Reported as a TEAE
timeFrame: Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable)
measure: Change from Baseline in Vital Signs
timeFrame: Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable)
measure: Change from Baseline in ECG Values
timeFrame: Baseline ()pre-dose through 14 days post-dose or 30 day safety follow-up visit (if applicable)
measure: Change from Baseline in QTc
timeFrame: Pre-dose through 24 hours post-dose
measure: Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: Tmax (Time of Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: AUC0-24 (Area under the Plasma Concentration-time Curve from Time Zero to 24 hours) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: 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
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: AUC0-inf (Area under the Plasma Concentration-time Curve from 0-time Extrapolated to Infinity) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: t1/2 (Elimination Half-life and Apparent Plasma Terminal Phase Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
measure: λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
timeFrame: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Other outcomes:
measure: Changes in Immune Regulatory Cells after a Single Dose of Entinostat, when given at a Supratherapeutic Dose, Relative to Placebo Control
timeFrame: Pre-dose through 14 days post-dose
measure: 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
timeFrame: Pre-dose through 14 days post-dose
Locations:
city: San Antonio
country: United States
facility: The START Center for Cancer Care
state: Texas
Study officials:
affiliation: Syndax Pharmaceuticals
name: Michael Meyers, MD, PhD
role: STUDY_DIRECTOR
References: