The addition of entinostat to an AI will result in a maximal abrogation of estrogen receptor-α mediated activity and inhibit mechanisms of resistance to the aromatase inhibitor. It is hypothesized that entinostat with continued AI will increase the estimated AI clinical benefit rate (CBR) from 5% to 25% with an acceptable safety profile.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Entinostat 5 mg PO every week
AI therapy at labeled dose and schedule as prescribed in clinical practice. AI therapies include: Arimidex® (anastrozole) 1 mg/day by mouth (PO), Fermara® (letrozole) 2.5 mg/day PO , Aromasin® (exemestane) 25 mg/day PO.
St. Vincent's University Hospital
Dublin, Ireland
The University of Birmingham
Birmingham, United Kingdom
Velindre Hospital - Whitchurch
Cardiff, United Kingdom
Whiston Hospital; Clatterbridge Centre for Oncology
Liverpool, United Kingdom
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) for 6 months as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.
Time frame: 6 months
Progression-Free Survival (PFS)
PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause.
Time frame: Up to 6, 28-day cycles
Objective Response Rate (ORR) During the First 6 Cycles of Study Treatment
ORR is defined as the percentage of participants with response during treatment classified as CR or PR, as assessed by the investigator based on RECIST, version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time frame: Up to 6, 28-day cycles
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. Abnormal clinical laboratory findings determined by the investigator to be clinically significant were recorded as AEs.
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University College London Hospitals
London, United Kingdom
Christie Hospital, Manchester Breast Centre
Manchester, United Kingdom
Time frame: Up to 6, 28-day cycles + 30 days