Clinical Trials /

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

NCT02820961

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Drug-Drug Interaction Study of <span class="go-doc-concept go-doc-intervention">Entinostat</span> and <span class="go-doc-concept go-doc-intervention">Exemestane</span> in Postmenopausal Women With <span class="go-doc-concept go-doc-alteration">ER+</span> Breast Cancer

Title

  • Brief Title: 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
  • Clinical Trial IDs

    NCT ID: NCT02820961

    ORG ID: SNDX-275-0130

    Trial Conditions

    Breast Cancer

    Estrogen Receptor Positive Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    entinostat SNDX-275, MS-275 Cohort 1, Cohort 2
    exemestane Aromasin, FCE-24304 Cohort 1, Cohort 2

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Active Comparator Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Each treatment cycle is 28 days. entinostat, 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. entinostat, exemestane

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 85 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Cmax, maximum plasma concentration

    Tmax, time at which maximum plasma concentration was observed

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

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

    T1/2, elimination half-life

    lambda z , apparent terminal phase elimination constant (z)

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

    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

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

    Secondary Outcome Measures

    Best overall tumor response

    Overall survival

    Trial 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