Trial Outcomes & Findings for Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing (NCT NCT00828854)

Last Updated: 2022-06-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

6 months

Results posted on

2022-06-30

Participant Flow

Participants took part in the study at 8 investigative sites in the United Kingdom and Ireland from 1 October 2008 to 24 November 2009.

Participants with a diagnosis of estrogen receptor-positive (ER+) breast cancer whose disease is progressing were enrolled to receive entinostat 5 mg in combination with continued aromatase Inhibitor (AI) therapy.

Participant milestones

Participant milestones
Measure	Entinostat 5 mg + AI Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Overall Study STARTED	27
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Entinostat 5 mg + AI Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Overall Study Disease Progression	17
Overall Study Adverse Event	9
Overall Study Reason not Specified	1

Baseline Characteristics

Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entinostat 5 mg + AI n=27 Participants Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Age, Continuous	68 years STANDARD_DEVIATION 7.0 • n=5 Participants
Age, Customized 45 to 64 years	7 Participants n=5 Participants
Age, Customized 65 to 74 years	15 Participants n=5 Participants
Age, Customized 75 years and older	5 Participants n=5 Participants
Sex: Female, Male Female	27 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	1 Participants n=5 Participants
Race (NIH/OMB) White	26 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
Region of Enrollment Ireland	9 participants n=5 Participants
Region of Enrollment United Kingdom	18 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Status Score=0	9 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Status Score=1	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Per-protocol Set included participants from the full analysis who met eligibility criteria, completed at least 2 cycles and who had baseline and post-baseline tumor assessments.

Outcome measures

Outcome measures
Measure	Entinostat 5 mg + AI n=26 Participants Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Clinical Benefit Rate (CBR)	15.4 percentage of participants Interval 4.4 to 34.9

SECONDARY outcome

Timeframe: Up to 6, 28-day cycles

Population: Per-protocol Set included participants from the full analysis who met eligibility criteria, completed at least 2 cycles and who had baseline and post-baseline tumor assessments

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.

Outcome measures

Outcome measures
Measure	Entinostat 5 mg + AI n=26 Participants Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Progression-Free Survival (PFS)	3.9 months Interval 1.9 to 5.6

SECONDARY outcome

Timeframe: Up to 6, 28-day cycles

Population: Per-protocol Set included participants from the full analysis who met eligibility criteria, completed at least 2 cycles and who had baseline and post-baseline tumor assessments

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.

Outcome measures

Outcome measures
Measure	Entinostat 5 mg + AI n=26 Participants Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Objective Response Rate (ORR) During the First 6 Cycles of Study Treatment	3.9 percentage of participants Interval 0.1 to 19.6

SECONDARY outcome

Timeframe: Up to 6, 28-day cycles + 30 days

Population: Safety Set included all participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Entinostat 5 mg + AI n=27 Participants Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Number of Participants With Adverse Events (AEs)	27 Participants

Adverse Events

Entinostat 5 mg + AI

Serious events: 15 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Entinostat 5 mg + AI n=27 participants at risk Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Pancytopenia	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial effusion	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
General disorders Adverse drug reaction	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory tract infection	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Hip fracture	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalemia	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Convulsion	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Spinal cord compression	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders VIth nerve paralysis	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	11.1% 3/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	3.7% 1/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Entinostat 5 mg + AI n=27 participants at risk Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.
General disorders Fatigue	55.6% 15/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	55.6% 15/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	48.1% 13/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Weight decreased	40.7% 11/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	37.0% 10/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Lethargy	29.6% 8/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	25.9% 7/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.9% 7/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	25.9% 7/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
General disorders Pain	22.2% 6/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	18.5% 5/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	18.5% 5/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Flatulence	18.5% 5/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	18.5% 5/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Platelet count decreased	18.5% 5/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Anorexia	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
General disorders Chest pain	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Neutrophil count decreased	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations White blood cell count decreased	14.8% 4/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Blood lactate dehydrogenase increased	11.1% 3/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Depression	11.1% 3/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	11.1% 3/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	11.1% 3/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Aspartate aminotransferase increased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Blood albumin decreased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Blood potassium increased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Blood urea increased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Depressed mood	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Eructation	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Gamma-glutamyltransferase increased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Haemoglobin decreased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Lip dry	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Infections and infestations Lower respiratory tract infection	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Investigations Lymphocyte count decreased	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Cardiac disorders Palpitations	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Purpura	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory tract infection	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	7.4% 2/27 • Up to 6, 28-day cycles + 30 days Safety Set included all participants who received at least 1 dose of study drug.

Additional Information

Michael Meyers, MD, PhD, Chief Medical Officer

Syndax Pharmaceuticals, Inc.

Phone: +1-646-690-7620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of the results of the multi-center Study shall not be made before the first multi-site publication by Sponsor or Publications Committee. No Public Presentation by Institution or Investigator will be made until Study Documentation/Results from all sites are received and analyzed by Sponsor. Separate publication by Investigator will be delayed for a period of 18 months until the initial publication by Committee or Sponsor, or a determination is made not to make such publication
Publication restrictions are in place

Restriction type: OTHER