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

NCT02820961 | Completed Phase 1

• 1 other identifier: SNDX-275-0130
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (9)

• Cmax, maximum plasma concentration

  Approximately 1 year

• Tmax, time at which maximum plasma concentration was observed

  Approximately 1 year

• AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration

  Approximately 1 year

• AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity

  Approximately 1 year

• T1/2, elimination half-life

  Approximately 1 year

• lambda z , apparent terminal phase elimination constant (λz)

  Approximately 1 year

• AUC0-τ where τ=168 hours for entinostat and τ=24 hours for exemestane

  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

  Approximately 1 year

• Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values

  Approximately 1 year

Secondary Outcomes (2)

• Best overall tumor response

  Approximately 2 years

• Overall survival

  Approximately 2 years

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Each treatment cycle is 28 days.

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.

Drug: entinostat; Drug: exemestane

Interventions

entinostat DRUG

An orally available histone deacetylases inhibitor (HDAC)

Also known as: SNDX-275, MS-275

Cohort 1; Cohort 2

exemestane DRUG

Aromatase inhibitor

Also known as: Aromasin, FCE-24304

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (3)

Sarah Cannon Research Institute HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Diseases

Interventions

entinostat; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael Meyers, MD, PhD

  Syndax Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 1, 2016
• Study Start: June 29, 2016
• Primary Completion: September 10, 2018
• Study Completion: July 12, 2021
• Last Updated: December 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)