Trial Outcomes & Findings for Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery (NCT NCT01234532)

Results Overview

Since the study was terminated early there was insufficient data for analysis and to recommend a phase II dose of entinostat in combination with anastrozole

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Duration of the study is 29 days followed by 30 days end of study assessment visit, up to 59 days

Results posted on

2022-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Entinostat & Anastrozole Neoadjuvant Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Duration of the study is 29 days followed by 30 days end of study assessment visit, up to 59 days

Population: Since the study was terminated early there was insufficient data for analysis and to recommend a phase II dose of entinostat in combination with anastrozole

Since the study was terminated early there was insufficient data for analysis and to recommend a phase II dose of entinostat in combination with anastrozole

Outcome measures

Outcome measures
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Recommended Phase II Dose of Entinostat in Combination With Anastrozole (Pilot)	NA mg Standard Deviation NA Data were below the lower limit of quantification

PRIMARY outcome

Timeframe: Participants were followed during the study and for 30 days post treatment, up to 59 days

To address the safety of the regimen, a maximum width 90% confidence interval for any grade 3 or higher toxicity will be approximately 30%. For 5 patients in this study, if the true unknown probability of a rare toxicity is 10%, the probability of observing 1 or more toxicities is 97%, and if the true toxicity rate is 5% then the probability of observing one or more rare toxicities is 83%.

Outcome measures

Outcome measures
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Number of Participants With Adverse Events	5 Participants

PRIMARY outcome

Timeframe: Baseline to the time of surgery, within 6 days after the last dose of entinostat, up to 35 days

Population: Since the study was terminated early there was insufficient data to do analysis

The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.

Outcome measures

Outcome measures
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Change in Proliferative Index (Ki67) (Phase II)	NA percentage of Ki 67 expression Data were below the lower limit of quantification

PRIMARY outcome

Timeframe: Baseline before the study treatment and at the time of surgery, up to 30 days

Population: Since the study was terminated early there was insufficient data to do the analysis

The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.

Outcome measures

Outcome measures
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Change in Estrogen-receptor (ER) Expression (Phase II)	NA percentage of (ER) expression Data were below the lower limit of quantification

SECONDARY outcome

Timeframe: Clinical response was assessed during the study treatment and before the surgery, up to 29 days

Population: Since the study was terminated early there was insufficient data to do the analysis

Rate of clinical response % of patients responding

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline before study treatment and at the time of surgery, up to 30 days

Population: Since the study was terminated early there was insufficient data to do the analysis

Will be treated as continuous variables. Multivariate analysis of variance may also be used to compare correlated biomarkers' expression. Correlation between biomarkers will be estimated and tested. The repeated measures model approach will be also used. Categorical outcome data (e.g., number of proteins expressed) will be recorded, proportions will be estimated and compared using the Fisher's exact test.

Outcome measures

Outcome measures
Measure	Entinostat & Anastrozole Neoadjuvant n=5 Participants Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery. entinostat: orally anastrozole: Given PO diagnostic laboratory biomarker analysis: Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.
Change in HER2	NA score on a scale Data were below the lower limit of quantification

SECONDARY outcome

Timeframe: Pathological response was assessed after the surgery, up to 59 days

Population: Since the study was terminated early there was insufficient data to do the analysis and data was not collected

Rate of Pathologic response % of patients responding

Outcome measures

Outcome data not reported

Adverse Events

Entinostat & Anastrozole Neoadjuvant

Serious events: 0 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Entinostat & Anastrozole Neoadjuvant n=5 participants at risk Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy.
Gastrointestinal disorders Nausea	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Gastrointestinal disorders Acid Reflux	40.0% 2/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Gastrointestinal disorders Acid Refulx	40.0% 2/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
General disorders Fatigue	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Gastrointestinal disorders Diarrhea	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
General disorders Hot Flashes	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Infections and infestations Myalgias	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Musculoskeletal and connective tissue disorders Arhralgias	20.0% 1/5 • Number of events 5 • 1 year, 3 months Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Additional Information

Katherine Tkaczuk, M.D.

University of Maryland, Baltimore

Phone: 410-328-2565

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place