Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With ER+ Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02820961
• Other study ID #: SNDX-275-0130
• Status: Completed
• Phase: Phase 1
• Start date: June 29, 2016
• Est. completion date: July 12, 2021

Study information

• Verified date: December 2021
• Source: Syndax Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: July 12, 2021
• Est. primary completion date: September 10, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Estrogen Receptor Positive Breast Cancer

Intervention

Drug:
• entinostat
An orally available histone deacetylases inhibitor (HDAC)
• exemestane
Aromatase inhibitor

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute HealthONE	Denver	Colorado
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax, maximum plasma concentration		Approximately 1 year
Primary	Tmax, time at which maximum plasma concentration was observed		Approximately 1 year
Primary	AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration		Approximately 1 year
Primary	AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity		Approximately 1 year
Primary	T1/2, elimination half-life		Approximately 1 year
Primary	lambda z , apparent terminal phase elimination constant (?z)		Approximately 1 year
Primary	AUC0-t where t=168 hours for entinostat and t=24 hours for exemestane		Approximately 1 year
Primary	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		Approximately 1 year
Primary	Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values		Approximately 1 year
Secondary	Best overall tumor response		Approximately 2 years
Secondary	Overall survival		Approximately 2 years