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

Syndax Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Estrogen Receptor Positive Breast Cancer

Treatments: Drug: exemestane; Drug: entinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02820961

SNDX-275-0130

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: Female

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 2 patient groups

Cohort 1

Active Comparator group

Description:

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

Treatment:

Drug: entinostat

Drug: exemestane

Cohort 2

Active Comparator group

Description:

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.

Treatment:

Drug: entinostat

Drug: exemestane