Clinical trial NCT02820961: Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With ER+ Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Estrogen Receptor Positive Breast Cancer
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
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-07-01
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Cmax, maximum plasma concentration
timeFrame: Approximately 1 year
measure: Tmax, time at which maximum plasma concentration was observed
timeFrame: Approximately 1 year
measure: AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration
timeFrame: Approximately 1 year
measure: AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity
timeFrame: Approximately 1 year
measure: T1/2, elimination half-life
timeFrame: Approximately 1 year
measure: lambda z , apparent terminal phase elimination constant (λz)
timeFrame: Approximately 1 year
measure: AUC0-τ where τ=168 hours for entinostat and τ=24 hours for exemestane
timeFrame: Approximately 1 year
measure: 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
timeFrame: Approximately 1 year
measure: Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values
timeFrame: Approximately 1 year
Secondary outcomes:
measure: Best overall tumor response
timeFrame: Approximately 2 years
measure: Overall survival
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Syndax Pharmaceuticals
name: Michael Meyers, MD, PhD
role: STUDY_DIRECTOR
References: