NeoplasmsPhase 1NCT02897778
Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
A Phase 1 study testing Entinostat in people with Neoplasms and Neoplasms, Glandular and Epithelial, run by Syndax Pharmaceuticals at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type
- What is being tested?
- Entinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2016to 13 Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The START Center for Cancer Care
San Antonio, Texas, 78229
About this study
Official title: A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
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.
Read the 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).
- Conditions
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms
- Being tested
- Entinostat, Placebo
- Keywords
- entinostat, solid tumor, Histone Deacetylase Inhibitors
- Medical subject headings
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Digestive System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntinostatDrug
Also called SNDX-275, MS-275
Single, supratherapeutic dose of entinostat given orally.
PlaceboDrug
Single dose of placebo-matching entinostat (containing inactive ingredients matching the appearance of the active product).
| Study group | Role | What they receive |
|---|---|---|
| Entinostat | Active comparator | Participants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions. Receives: Drug: Entinostat |
| Placebo | Placebo comparator | Participants received a single dose of placebo-matching entinostat under fasted conditions. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Heart Rate (HR)
Heart rate measured in beats per minute (bpm).
Measured: 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).
Measured: Baseline (pre-dose) through 24 hours post-dose
Change from Baseline in T-Cell Morphology
Measured: Baseline (pre-dose) through 24 hours post-dose
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline ()pre-dose through 14 days post-dose or 30 day safety follow-up visit (if applicable)
Change from Baseline in QTc
Measured: Pre-dose through 24 hours post-dose
Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose
Measured: Pre-dose and multiple time-points 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
Measured: Pre-dose and multiple time-points 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
Measured: Pre-dose and multiple time-points 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
Measured: Pre-dose and multiple time-points 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
Measured: Pre-dose and multiple time-points 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
Measured: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose
Measured: Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study start24 Aug 2016
- Primary completion13 Mar 2017
- Study completion13 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Meyers, MD, PhD, Study director, Syndax Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02897778
- Sponsor's protocol ID
- SNDX-275-0140
- Status last verified
- Apr 2022
- First submitted
- 20 Aug 2016
- Last updated
- 28 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02897778
- Acronym / sponsor ID
- SNDX-275-0140
- Conditions
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms
- Keywords
- entinostat, solid tumor, Histone Deacetylase Inhibitors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2016 (actual)
- Primary completion
- 13 Mar 2017 (actual)
- Study completion
- 13 Mar 2017 (actual)
- First posted
- 13 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entinostat | Active comparator | Drug: EntinostatParticipants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received a single dose of placebo-matching entinostat under fasted conditions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntinostatAlso: SNDX-275, MS-275Single, supratherapeutic dose of entinostat given orally. | Drug | Entinostat |
| PlaceboSingle dose of placebo-matching entinostat (containing inactive ingredients matching the appearance of the active product). | Drug | Placebo |
Primary outcome
Change from Baseline in Heart Rate (HR)
Time frame: Baseline (pre-dose) through 24 hours post-dose
Heart rate measured in beats per minute (bpm).
Change from Baseline in Electrocardiogram Procedures
Time frame: Baseline (pre-dose) through 24 hours post-dose
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
Time frame: Baseline (pre-dose) through 24 hours post-dose
12 secondary outcomes
Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)
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
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
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
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
Time frame: Pre-dose and multiple time-points 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 and multiple time-points 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 and multiple time-points 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 and multiple time-points 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 and multiple time-points 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 and multiple time-points 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 and multiple time-points through 24 hours post-dose and 14 days post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Meyers, MD, PhD study director
Syndax Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Entinostat in people with Neoplasms and Neoplasms, Glandular and Epithelial, run by Syndax Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in Heart Rate (HR) (time frame: Baseline (pre-dose) through 24 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2022.