Breast CancerPhase 1NCT02820961
Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With ER+ Breast Cancer
A Phase 1 study testing entinostat and exemestane in people with Breast Cancer and Estrogen Receptor Positive Breast Cancer, run by Syndax Pharmaceuticals at 3 sites in United States.
Trial summary
The purpose of this study is to determine the effect of exemestane on the pharmacokinetics (PK) of entinostat and to determine the effect of entinostat on the PK of exemestane in patients with locally recurrent or metastatic estrogen receptor positive (ER+) breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Breast Cancer, Estrogen Receptor Positive Breast Cancer
- What is being tested?
- entinostat and exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Jun 2016to 12 Jul 2021
- 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 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal female patients
- Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and have locally recurrent or metastatic disease that has progressed to where the patient is a candidate to receive exemestane as determined by the Investigator
- Patients receiving palliative radiation at the non-target lesions must be clinically stable prior to receiving the first dose of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patient must have acceptable, applicable laboratory requirements
- Patients may have a history of brain metastasis provided certain protocol criteria are met
- Able to understand and give written informed consent and comply with study procedures
Who cannot join
- Rapidly progressive or life-threatening metastases
- Inability to swallow oral medications or gastrointestinal (GI) malabsorption syndromes
- History of significant GI surgery as determined by Investigator
- A medical condition that precludes adequate study treatment or increases patient risk
- Currently enrolled in (or completed within 30 days prior to study drug administration) another investigational drug study
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Sarah Cannon Research Institute HealthONE
Denver, Colorado, 80218
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
Official title: A Phase 1, Two-Cohort, Open-Label, Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer
The purpose of this study is to determine the effect of exemestane on the pharmacokinetics (PK) of entinostat and to determine the effect of entinostat on the PK of exemestane in patients with locally recurrent or metastatic estrogen receptor positive (ER+) breast cancer. Additionally, this study will evaluate the safety and tolerability of entinostat in combination with exemestane, and assess the effectiveness of entinostat in combination with exemestane in terms of best overall response and overall survival.
Read the detailed description
SNDX-275-0130 is a Phase 1, two-cohort, open-label, drug-drug interaction study of entinostat and exemestane. All patients will be enrolled into one of two cohorts to receive either entinostat monotherapy followed by entinostat plus exemestane (Cohort 1), or exemestane monotherapy followed by exemestane plus entinostat (Cohort 2).
The cohorts will enroll sequentially, meaning that Cohort 1 will enroll prior to Cohort 2. Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. In both Cohorts, each treatment cycle will be 28 days. Patients will participate in only one cohort.
All patients will be assessed at Screening and at specified times during the conduct of the study using standard clinical and laboratory assessment. Patients will also be assessed for tumor response per standard of care after the Screening Period. Response to treatment will be assessed by computerized tomography (CT), magnetic resonance imaging (MRI) and bone scans as appropriate. Patients will continue receiving their appropriate cycles of study treatment until tumor progression or adverse events (AEs) occur which necessitate discontinuing therapy as determined by the Investigator.
- Being tested
- entinostat, exemestane
- Keywords
- Breast Neoplasms, Breast Diseases, Exemestane, Protein Kinase Inhibitors, Aromatase Inhibitors, entinostat, Cancer of the Breast, Metastatic Breast Cancer, Hormone Receptor Positive Breast Cancer, Estrogen Receptor, ER+ Breast Cancer, Breast Tumor
- Medical subject headings
- Breast Neoplasms, Breast Diseases
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
An orally available histone deacetylases inhibitor (HDAC)
exemestaneDrug
Also called Aromasin, FCE-24304
Aromatase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Active comparator | Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Each treatment cycle is 28 days. Receives: Drug: entinostat; Drug: exemestane |
| Cohort 2 | Active comparator | Cohort 2 will enroll when Cohort 1 enrollment is complete. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. Each treatment cycle is 28 days. Receives: Drug: entinostat; Drug: exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax, maximum plasma concentration
Measured: Approximately 1 year
Tmax, time at which maximum plasma concentration was observed
Measured: Approximately 1 year
AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration
Measured: Approximately 1 year
AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity
Measured: Approximately 1 year
T1/2, elimination half-life
Measured: Approximately 1 year
lambda z , apparent terminal phase elimination constant (λz)
Measured: Approximately 1 year
AUC0-τ where τ=168 hours for entinostat and τ=24 hours for exemestane
Measured: Approximately 1 year
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs resulting in the permanent discontinuation of study drug, and deaths occurring within 30-days of the last dose of study drug
Measured: Approximately 1 year
Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values
Measured: Approximately 1 year
Secondary outcomes (2)
Best overall tumor response
Measured: Approximately 2 years
Overall survival
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2016 (estimated)
- Study start29 Jun 2016
- Primary completion10 Sep 2018
- Study completion12 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 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
- NCT02820961
- Sponsor's protocol ID
- SNDX-275-0130
- Status last verified
- Dec 2021
- First submitted
- 29 Jun 2016
- Last updated
- 15 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Two-Cohort, Open-Label, Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer
- ClinicalTrials.gov ID
- NCT02820961
- Acronym / sponsor ID
- SNDX-275-0130
- Keywords
- Breast Neoplasms, Breast Diseases, Exemestane, Protein Kinase Inhibitors, Aromatase Inhibitors, entinostat, Cancer of the Breast, Metastatic Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2016 (actual)
- Primary completion
- 10 Sep 2018 (actual)
- Study completion
- 12 Jul 2021 (actual)
- First posted
- 1 Jul 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 determine the effect of exemestane on the pharmacokinetics (PK) of entinostat and to determine the effect of entinostat on the PK of exemestane in patients with locally recurrent or metastatic estrogen receptor positive (ER+) breast cancer. Additionally, this study will evaluate the safety and tolerability of entinostat in combination with exemestane, and assess the effectiveness of entinostat in combination with exemestane in terms of best overall response and overall survival.
Detailed description
SNDX-275-0130 is a Phase 1, two-cohort, open-label, drug-drug interaction study of entinostat and exemestane. All patients will be enrolled into one of two cohorts to receive either entinostat monotherapy followed by entinostat plus exemestane (Cohort 1), or exemestane monotherapy followed by exemestane plus entinostat (Cohort 2).
The cohorts will enroll sequentially, meaning that Cohort 1 will enroll prior to Cohort 2. Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. In both Cohorts, each treatment cycle will be 28 days. Patients will participate in only one cohort.
All patients will be assessed at Screening and at specified times during the conduct of the study using standard clinical and laboratory assessment. Patients will also be assessed for tumor response per standard of care after the Screening Period. Response to treatment will be assessed by computerized tomography (CT), magnetic resonance imaging (MRI) and bone scans as appropriate. Patients will continue receiving their appropriate cycles of study treatment until tumor progression or adverse events (AEs) occur which necessitate discontinuing therapy as determined by the Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Active comparator | Drug: entinostat, Drug: exemestaneCohort 1 will evaluate exemestane's effect on the PK of entinostat. Each treatment cycle is 28 days. |
| Cohort 2 | Active comparator | Drug: entinostat, Drug: exemestaneCohort 2 will enroll when Cohort 1 enrollment is complete. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. Each treatment cycle is 28 days. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Postmenopausal female patients
- Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and have locally recurrent or metastatic disease that has progressed to where the patient is a candidate to receive exemestane as determined by the Investigator
- Patients receiving palliative radiation at the non-target lesions must be clinically stable prior to receiving the first dose of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patient must have acceptable, applicable laboratory requirements
Key exclusion criteria (5 listed)
- Rapidly progressive or life-threatening metastases
- Inability to swallow oral medications or gastrointestinal (GI) malabsorption syndromes
- History of significant GI surgery as determined by Investigator
- A medical condition that precludes adequate study treatment or increases patient risk
- Currently enrolled in (or completed within 30 days prior to study drug administration) another investigational drug study
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-275An orally available histone deacetylases inhibitor (HDAC) | Drug | Cohort 1, Cohort 2 |
| exemestaneAlso: Aromasin, FCE-24304Aromatase inhibitor | Drug | Cohort 1, Cohort 2 |
Primary outcome
Cmax, maximum plasma concentration
Time frame: Approximately 1 year
Tmax, time at which maximum plasma concentration was observed
Time frame: Approximately 1 year
AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration
Time frame: Approximately 1 year
AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity
Time frame: Approximately 1 year
T1/2, elimination half-life
Time frame: Approximately 1 year
lambda z , apparent terminal phase elimination constant (λz)
Time frame: Approximately 1 year
AUC0-τ where τ=168 hours for entinostat and τ=24 hours for exemestane
Time frame: Approximately 1 year
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs resulting in the permanent discontinuation of study drug, and deaths occurring within 30-days of the last dose of study drug
Time frame: Approximately 1 year
Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values
Time frame: Approximately 1 year
2 secondary outcomes
Best overall tumor response
Time frame: Approximately 2 years
Overall survival
Time frame: Approximately 2 years
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 15 Dec 2021.
- Individual participant dataSharing planned: No
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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
3 sites 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 and exemestane in people with Breast Cancer and Estrogen Receptor Positive Breast Cancer, run by Syndax Pharmaceuticals at 3 sites 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 7 inclusion and 5 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 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. 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?
Cmax, maximum plasma concentration (time frame: Approximately 1 year). The study lists 9 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 15 Dec 2021.