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Male Breast CarcinomaPhase 2NCT01349959

Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer

A Phase 2 study testing Azacitidine, Entinostat and Laboratory Biomarker Analysis in people with Male Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well giving azacitidine and entinostat work in treating patients with advanced breast cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine, Entinostat and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
7 sitesUnited States
Study dates
15 Aug 2011to 7 Nov 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have histologically or cytologically confirmed adenocarcinoma of the breast triple-negative (ER-, progesterone receptor [PR]-, human epidermal growth factor receptor 2 [HER2]-) or hormone positive/ HER2-, with evidence of locally advanced and inoperable or metastatic disease (American Joint Committee on Cancer [AJCC] Stage IV)
  • NOTE: Triple-negative patients will be defined per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines; these guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls
  • A patient who has a change in receptor status (e.g., PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study based upon the clinical course at the discretion of the Study Chair; for HER2 assessment, a negative result is an immuno-histochemistry staining of 0 or 1+, a fluorescence in situ hybridization (FISH) result of less than 4.0 HER2 gene copies per nucleus, or a FISH ratio of less than 1.8
  • Patients with triple negative disease must have progressed through at least 1 prior chemotherapy regimen (administered in the adjuvant or metastatic setting); hormone receptor-positive patients must have progressed through two lines of hormonal therapy (administered in the adjuvant or metastatic setting), unless otherwise eligible as per below, and at least 1 prior chemotherapy regimen (administered in the adjuvant or metastatic setting) with no known curative options available
  • NOTE: Patients with hormone receptor-positive disease may be considered eligible if deemed clinically hormone-resistant taking into consideration the rate of progression of disease or a short interval of time on first line hormonal therapy before progression, or if intolerant of hormonal therapy such that further hormonal therapy will not be considered as part of the treatment strategy
  • In patients with metastatic disease in the liver, liver disease burden is limited to no more than 30% of total liver volume as assessed by local review
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  • Patients must have measurable disease
  • Life expectancy of >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Hemoglobin (HgB) >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); an exception to this may be allowed for participants with Gilbert's syndrome with documented approval by the Protocol Chair
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
  • Creatinine =< institutional ULN or creatinine clearance >= 60 mL/min using the Modified Cockcroft-Gault formula
  • Negative (serum or urine) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Patient must have an accessible tumor lesion from which a biopsy specimen can be obtained; NOTE: if baseline biopsy is attempted and is unsuccessful (eg, patient intolerance, inadequate tissue), the patient will still be considered eligible for the study
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to provide tissue and blood samples for mandatory translational research
  • Willingness to return to the enrolling institution for follow-up

Who cannot join

  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • NOTE: should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Any of the following:
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  • Chemotherapy < 3 weeks prior to registration
  • Hormone therapy < 3 weeks prior to registration
  • Radiotherapy < 3 weeks prior to registration
  • Surgery < 3 weeks prior to registration
  • Nitrosoureas/mitomycin C < 6 weeks prior to registration
  • Trastuzumab < 6 weeks prior to registration
  • Bevacizumab < 6 weeks prior to registration
  • Those who have not recovered from acute adverse events to grade < 2 or baseline due to agents administered, with exception of alopecia, unless approved by the Protocol Chair
  • NOTE: concurrent bisphosphonate therapy is allowed; concurrent ovarian suppression therapy (i.e., Lupron or Zoladex) is also allowed at the discretion of the Protocol Chair/designee
  • Any other ongoing investigational agents
  • Known sensitivity to 5-AZA, entinostat or mannitol
  • Uncontrolled intercurrent illness that in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure (New York Heart Association [NYHA] class II or above)
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Other co-morbid systemic illness or other severe concurrent disease
  • Active malignancy other than breast cancer =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Received prior treatment with HDAC (histone deacetylase) inhibitors or demethylating agents =< 2 weeks prior to registration
  • Unstable brain metastases; NOTE: patients with brain metastases must have stable neurologic status and magnetic resonance imaging (MRI) imaging following local therapy (surgery or radiation) for at least 4 weeks, with no dexamethasone requirement (stable low dose dexamethasone allowed at discretion of Study Chair); patients with leptomeningeal disease are not eligible
  • Patient taking valproic acid
  • Patient who cannot swallow tablets

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Unity Hospital

    Fridley, Minnesota, 55432

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

Other trials in United States

About this study

Official title: Phase II Study of Azacitidine and Entinostat (SNDX-275) in Patients With Advanced Breast Cancer

This phase II trial studies how well giving azacitidine and entinostat work in treating patients with advanced breast cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST) criteria of the combination of azacitidine (5-AZA) and entinostat in women with advanced breast cancer; triple-negative and hormone-refractory.

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of the combination of 5-AZA and entinostat in women with advanced breast cancer.

II. To determine progression-free survival, overall survival, and clinical benefit rate of the combination of 5-AZA and entinostat.

TERTIARY OBJECTIVES:

  1. To collect safety and toxicity data as well as the feasibility and response rate where hormonal therapy is added to the combination under investigation at the time of progressive disease. (Exploratory) II. To determine the pharmacokinetic profile of 5-AZA (full profile) and entinostat (trough concentrations) in patients with advanced breast cancer. (Exploratory) III. To assess serum cytidine deaminase pharmacogenetics and phenotypic activity as a potential biomarker of response to 5-AZA. (Exploratory) IV. To evaluate baseline and change in candidate gene re-expression (e.g., estrogen receptor [ER] alpha, retinoic acid receptor [RAR] beta) in malignant tissue obtained from selected patients through fine-needle aspiration (FNA) and core biopsy, prior to and following combination therapy. (Exploratory) V. To evaluate baseline and change in gene methylation silencing in circulating deoxyribonucleic acid (DNA) obtained prior to and following combination therapy. (Exploratory) VI. To evaluate baseline and change in gene methylation in malignant tissue obtained through FNA and core biopsy. (Exploratory)

OUTLINE: This is a multicenter study.

Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10, and entinostat orally (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.

After completion of study therapy, patients are followed up every 3-6 months for up to 3 years.

Being tested
Azacitidine, Entinostat, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine

    Given SC

  • EntinostatDrug

    Also called HDAC inhibitor SNDX-275, MS 27-275, MS 275, MS-275

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01349959
Study groupRoleWhat they receive
Treatment (entinostat and azacitidine)ExperimentalPatients 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.
Receives: Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Clinical Benefit Rate

    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.

    Measured: Up to 3 years

  2. Overall Survival

    Median number of months alive, estimated by Kaplan-Meier method.

    Measured: Up to 3 years

  3. Progression-free Survival (PFS)

    Median number of months without progression. Estimated using the method of Kaplan-Meier.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2011 (estimated)
  2. Study start15 Aug 2011
  3. Primary completion27 Mar 2014
  4. Study completion7 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01349959
Sponsor's protocol ID
NCI-2011-02585
Other IDs
NCI-2011-02585, CDR0000698726, SKCCC J1107, 8822, N01CM00099, N01CM00038, N01CM62205, P30CA006973
Status last verified
Apr 2025
First submitted
6 May 2011
Last updated
27 Apr 2025
Data monitoring committee
Yes

Publications

  • Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014 Feb 15;5(3):587-98. doi: 10.18632/oncotarget.1782.

    PubMed 24583822

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine, Entinostat and Laboratory Biomarker Analysis in people with Male Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01349959, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025; AzTrials last refreshed its copy on 26 Oct 2026.

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