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

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ClinicalTrials.gov Identifier: NCT02897778
Recruitment Status : Completed
First Posted : September 13, 2016
Last Update Posted : April 17, 2017
Sponsor:
Information provided by (Responsible Party):
Syndax Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 20, 2016
First Posted Date  ICMJE September 13, 2016
Last Update Posted Date April 17, 2017
Actual Study Start Date  ICMJE August 2016
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
  • Change from baseline on heart rate (HR) when entinostat is given at a supratherapeutic dose [ Time Frame: Pre-dose through 24 hours post-dose ]
    Change from baseline HR
  • Change from baseline on electrocardiogram procedures when entinostat is given at a supratherapeutic dose [ Time Frame: Pre-dose through 24 hours post-dose ]
    Change from baseline QT interval corrected for heart rate (Qtc), PR interval (PR), QRS complex (QRS), and T-wave morphology
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02897778 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
  • Incidence of treatment-emergent adverse events (TEAES) and serious adverse events (SAEs) [ Time Frame: Informed consent through 30 days post-dose or through resolution of acute toxicities ]
  • Change from baseline in laboratory values [ Time Frame: Baseline through 14 days post-dose or 30 day safety follow-up visit (if applicable) ]
    Note: Safety data will continue to be followed in the SNDX-275-0141 roll-over study
  • Change from baseline in vital signs [ Time Frame: Baseline through 14 days post-dose or 30 day safety follow-up visit (if applicable) ]
    Note: Safety data will continue to be followed in the SNDX-275-0141 roll-over study
  • Change from baseline in ECG values [ Time Frame: Baseline through 14 days post-dose or 30 day safety follow-up visit (if applicable) ]
    Note: Safety data will continue to be followed in the SNDX-275-0141 roll-over study
  • Relationship between entinostat plasma concentrations and placebo controlled change from baseline QTc [ Time Frame: Pre-dose through 24 hours post-dose ]
  • Cmax (maximum plasma concentration) of entinostat when given as a single supratherapeutic dose [ Time Frame: Pre-dose through 24 hours post-dose and 14 days post-dose ]
  • Tmax (time of maximum plasma concentration) of entinostat when given as a single supratherapeutic dose [ Time Frame: Pre-dose through 24 hours post-dose and 14 days post-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 [ Time Frame: Pre-dose through 24 hours post-dose and 14 days post-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 [ Time Frame: Pre-dose 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 [ Time Frame: Pre-dose 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 [ Time Frame: Pre-dose through 24 hours post-dose and 14 days post-dose ]
  • λz (terminal elimination rate constant) of entinostat when given as a single supratherapeutic dose [ Time Frame: Pre-dose through 24 hours post-dose and 14 days post-dose ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 7, 2016)
  • 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 ]
  • 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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Brief Summary The purpose of this study is to evaluate the effect of entinostat on heart rate and other electrocardiogram 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Entinostat
    Single, supratherapeutic dose of entinostat given orally
    Other Names:
    • SNDX-275
    • MS-275
  • Other: Placebo
    Single dose of Placebo containing inactive ingredients matching the appearance of the active product (entinostat).
Study Arms  ICMJE
  • Active Comparator: Entinostat
    15 patients will be randomized to receive a single, supratherapeutic dose of entinostat
    Intervention: Drug: Entinostat
  • Placebo Comparator: Placebo
    15 patients will be randomized to receive a single dose of placebo
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 14, 2017)
37
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2016)
30
Actual Study Completion Date  ICMJE April 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02897778
Other Study ID Numbers  ICMJE SNDX-275-0140
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data will be reviewed throughout the study by the sponsor, CRO assisting with SAE management, and routine monitoring to safeguard the interests of trial patients and to assess the safety of the interventions administered during the trial
Responsible Party Syndax Pharmaceuticals
Study Sponsor  ICMJE Syndax Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael Meyers, MD, PhD Syndax Pharmaceuticals, Inc.
PRS Account Syndax Pharmaceuticals
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP