Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer

NCT01349959 | Completed Phase 2 Results DMC

• 11 other identifiers: NCI-2011-02585CDR0000698726SKCCC J11078822N01CM00099N01CM00038N01CM62205P30CA006973U01CA099168U01CA070095UM1CA186691
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Male Breast Carcinoma; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (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.

  Up to 3 years

Secondary Outcomes (3)

• Clinical Benefit Rate

  Up to 3 years

• Overall Survival

  Up to 3 years

• Progression-free Survival (PFS)

  6 months

Other Outcomes (5)

• 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)

  Baseline to up to 8 weeks

• Circulating DNA Evaluated Using QM-MSP

  Up to 8 weeks

• Confirmed Response Rate to Azacitidine and Entinostat Plus the Addition of Hormone Therapy

  Up to 3 years

Study Arms (1)

Treatment (entinostat and azacitidine)

EXPERIMENTAL

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.

Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (entinostat and azacitidine)

Entinostat DRUG

Given PO

Also known as: HDAC inhibitor SNDX-275, MS 27-275, MS 275, MS-275, MS275, SNDX 275, SNDX-275, SNDX275

Treatment (entinostat and azacitidine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (entinostat and azacitidine)

Pharmacological Study OTHER

Correlative studies

Treatment (entinostat and azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• 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.

  PMID: 24583822 DERIVED

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Azacitidine; entinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Clinical Research Office
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

jhcccro@jhmi.edu

410-955-8866

Study Officials

• Vered Stearns

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2011
• First Posted: May 9, 2011
• Study Start: August 15, 2011
• Primary Completion: March 27, 2014
• Study Completion: November 7, 2023
• Last Updated: April 27, 2025
• Results First Posted: March 17, 2016

Record last verified: 2025-04

Locations

US (7)