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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

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.

Condition or disease Intervention/treatment Phase
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 Drug: Entinostat Other: Placebo Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
Actual Study Start Date : August 2016
Actual Primary Completion Date : March 2017
Actual Study Completion Date : April 2017

Arm Intervention/treatment
Active Comparator: Entinostat
15 patients will be randomized to receive a single, supratherapeutic dose of entinostat
Drug: Entinostat
Single, supratherapeutic dose of entinostat given orally
Other Names:
  • SNDX-275
  • MS-275

Placebo Comparator: Placebo
15 patients will be randomized to receive a single dose of placebo
Other: Placebo
Single dose of Placebo containing inactive ingredients matching the appearance of the active product (entinostat).




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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 ]
  2. 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

  3. 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

  4. 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

  5. Relationship between entinostat plasma concentrations and placebo controlled change from baseline QTc [ Time Frame: Pre-dose through 24 hours post-dose ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]

Other Outcome Measures:
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02897778


Locations
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United States, Texas
The START Center for Cancer Care
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
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Study Director: Michael Meyers, MD, PhD Syndax Pharmaceuticals, Inc.

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Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02897778     History of Changes
Other Study ID Numbers: SNDX-275-0140
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: April 17, 2017
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
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

Keywords provided by Syndax Pharmaceuticals:
entinostat
solid tumor
Histone Deacetylase Inhibitors

Additional relevant MeSH terms:
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Neoplasms
Lung Diseases
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Breast Diseases
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms by Histologic Type
Thoracic Neoplasms
Neoplasms, Glandular and Epithelial
Respiratory Tract Neoplasms
Bronchial Neoplasms
Endocrine Gland Neoplasms
Kidney Neoplasms
Respiratory Tract Diseases
Neoplasms by Site
Skin Diseases
Carcinoma, Bronchogenic
Digestive System Diseases
Gastrointestinal Diseases
Bronchial Diseases
Endocrine System Diseases
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Entinostat
Histone Deacetylase Inhibitors
Antineoplastic Agents