Trial Outcomes & Findings for Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer (NCT NCT01349959)
NCT ID: NCT01349959
Last Updated: 2025-04-27
Results Overview
Percentage of participants with complete or partial response will be estimated independently for each cohort by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
Up to 3 years
Results posted on
2025-04-27
Participant Flow
58 consented, 18 screen failed and did not receive study treatment
Participant milestones
| Measure |
Treatment (Entinostat and Azacitidine)
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Treatment (Entinostat and Azacitidine)
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
Baseline Characteristics
Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 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
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 3 yearsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Percentage of participants with complete or partial response will be estimated independently for each cohort by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Confirmed Response Rate (Percentage of Participants With Complete or Partial Response Noted as the Objective Status on Two Consecutive Evaluations at Least 4 Weeks Apart) Assessed by RECIST
Triple-negative Breast Cancer (TNBC)
|
0 percentage of participants
No clinical response was observed in participants with TNBC.
|
|
Confirmed Response Rate (Percentage of Participants With Complete or Partial Response Noted as the Objective Status on Two Consecutive Evaluations at Least 4 Weeks Apart) Assessed by RECIST
Hormone-resistant Breast Cancer (HRBC)
|
4 percentage of participants
Interval 0.0 to 19.0
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Clinical benefit rate estimated by the number of patients who achieve a confirmed response plus the number of patients who have stable disease for a duration of at least 6 months divided by the total number of evaluable patients. All evaluable patients will be used for this analysis.
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Clinical Benefit Rate
TNBC
|
0 Participants
|
|
Clinical Benefit Rate
HRBC
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Median number of months alive, estimated by Kaplan-Meier method.
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Overall Survival
TNBC
|
6.6 months
Interval 2.0 to 10.3
|
|
Overall Survival
HRBC
|
12.6 months
Interval 6.3 to 16.3
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Median number of months without progression. Estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Progression-free Survival (PFS)
TNBC
|
1.4 months
Interval 0.9 to 1.8
|
|
Progression-free Survival (PFS)
HRBC
|
1.8 months
Interval 1.7 to 1.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to up to 8 weeksPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC). However, data was only evaluable in 19/40 participants (5/13 TNBC, and 14/40 HRBC).
Number of participants with a change in candidate gene re-expression of ER-alpha and RAR beta evaluated by reverse transcriptase polymerase chain reaction (RT-PCR).
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=19 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Number of Participants With Change in Expression of Relevant Genes (e.g., ER Alpha and RAR Beta) Evaluated by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
TNBC
|
0 Participants
|
|
Number of Participants With Change in Expression of Relevant Genes (e.g., ER Alpha and RAR Beta) Evaluated by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
HRBC
|
14 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 8 weeksData will also be graphically displayed showing trend in median values across time. Nonparametric Wilcoxon signed rank tests will be used to determine whether or not the data shows evidence of changes from baseline.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 3 yearsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Will be estimated in each cohort. All evaluable patients who receive hormonal therapy will be used for this analysis.
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Confirmed Response Rate to Azacitidine and Entinostat Plus the Addition of Hormone Therapy
TNBC
|
0 Participants
|
|
Confirmed Response Rate to Azacitidine and Entinostat Plus the Addition of Hormone Therapy
HRBC
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 3 yearsPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Feasibility of the Addition of Hormone Therapy, Evaluated by Calculating the Number of Patients With Disease Progression That go on to Receive Hormonal Therapy
TNBC
|
4 Participants
|
|
Feasibility of the Addition of Hormone Therapy, Evaluated by Calculating the Number of Patients With Disease Progression That go on to Receive Hormonal Therapy
HRBC
|
12 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 8 weeksPopulation: There were 13/40 participants with triple-negative breast cancer (TNBC) and 27/40 participants with hormone-resistant breast cancer (HRBC).
Outcome measures
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 Participants
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Number of Participants With Change in Gene Methylation Evaluated Using Quantitative Multiple Methylation-specific Polymerase Chain Reaction (QM-MSP)
TNBC
|
0 Participants
|
|
Number of Participants With Change in Gene Methylation Evaluated Using Quantitative Multiple Methylation-specific Polymerase Chain Reaction (QM-MSP)
HRBC
|
14 Participants
|
Adverse Events
Treatment (Entinostat and Azacitidine)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 33 deaths
Serious adverse events
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 participants at risk
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
5.0%
2/40 • Number of events 2 • 1 year
CTCAE criteria
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
2/40 • Number of events 2 • 1 year
CTCAE criteria
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Progression
|
5.0%
2/40 • Number of events 2 • 1 year
CTCAE criteria
|
|
General disorders
Death
|
2.5%
1/40 • Number of events 1 • 1 year
CTCAE criteria
|
|
Vascular disorders
Thromboembolic event
|
5.0%
2/40 • Number of events 2 • 1 year
CTCAE criteria
|
|
Investigations
White blood cell decreased
|
2.5%
1/40 • Number of events 1 • 1 year
CTCAE criteria
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.0%
2/40 • Number of events 2 • 1 year
CTCAE criteria
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
2.5%
1/40 • Number of events 1 • 1 year
CTCAE criteria
|
|
Infections and infestations
Skin Infection
|
2.5%
1/40 • Number of events 1 • 1 year
CTCAE criteria
|
|
Investigations
Neutrophil count decreased
|
2.5%
1/40 • Number of events 1 • 1 year
CTCAE criteria
|
Other adverse events
| Measure |
Treatment (Entinostat and Azacitidine)
n=40 participants at risk
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
Azacitidine: Given SC
Entinostat: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
15.0%
6/40 • 1 year
CTCAE criteria
|
Additional Information
Clinical Research Office
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phone: 410-955-8866
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60