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Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

Primary Purpose

Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
azacitidine
laboratory biomarker analysis
immunohistochemistry staining method
polymerase chain reaction
western blotting
nucleic acid sequencing
therapeutic conventional surgery
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Resectable tumor measuring 2 cm or more
  • Histologically documented triple negative invasive breast cancer characterized by 0% Immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for PR-alpha, and no amplification of HER2/neu by fluorescence in situ hybridization (FISH); standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and PR-beta
  • Southwest Oncology Group (SWOG) performance status of less than or equal to 1
  • Absolute neutrophil count (ANC) >= 1500/μL
  • Hemoglobin (Hgb) >= 9 g/dL
  • Platelets >= 100,000/uL
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x upper limit normal (ULN) or =< 5.0 x ULN in patients with liver metastases
  • Creatinine =< 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min
  • Albumin >= 3 g/dL
  • Potassium >= lower limit normal (LLN)
  • Phosphorous >= LLN
  • Calcium >= LLN
  • Magnesium > LLN
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment
  • Accessible for treatment and follow-up
  • Written informed consent prior to study entry

Exclusion Criteria:

  • HER2/neu amplification by FISH
  • Concurrent neoadjuvant treatment with chemotherapy, endocrine therapy, or radiotherapy
  • Known hypersensitivity to azacitidine or mannitol
  • Preexisting hepatic impairment or renal impairment
  • Intent to receive additional neoadjuvant therapy prior to surgery
  • Concurrent use of an histone deacetylase (HDAC) inhibitor or hydralazine
  • Known diagnosis of human immunodeficiency virus (HIV) infection
  • Major surgery < 4 weeks prior to starting study drug
  • Pregnant or breastfeeding or female of reproductive potential not using an effective method of birth control
  • Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase inhibitors) within 6 months of study entry
  • Underlying medical, psychiatric or social conditions that would preclude patient from receiving treatment

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment

    Arm Description

    See Detailed Description

    Outcomes

    Primary Outcome Measures

    Percent of participants with ER/PR response after receiving 10 doses of 5-Azacitidine

    Secondary Outcome Measures

    Full Information

    First Posted
    February 2, 2011
    Last Updated
    February 5, 2014
    Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01292083
    Brief Title
    Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery
    Official Title
    A Pilot Clinical Trial to Evaluate the Biological Activity of 5-azacitidine on ER and PR Expression in Triple Negative Invasive Breast Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    No accrual last 2 years
    Study Start Date
    January 2011 (undefined)
    Primary Completion Date
    March 2013 (Actual)
    Study Completion Date
    March 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This clinical trial studies azacitidine in treating patients with triple negative stage I-IV invasive breast cancer that can be removed by surgery. 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.
    Detailed Description
    PRIMARY OBJECTIVES: I. To evaluate the ability of deoxyribonucleic acid (DNA) methylation inhibition using 5-azacitidine to induce expression of the estrogen receptor (ER) and progesterone receptor (PR) genes in solid human triple negative invasive breast cancer. SECONDARY OBJECTIVES: I. To determine the effect of systemic 5-azacitidine therapy on the expression of other methylated genes in triple negative invasive breast cancer using an Illumina GoldenGate array. OUTLINE: Patients receive azacitidine intravenously (IV) over 10-40 minutes 5 days a week for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo definitive breast surgery within 12 days of the last dose of azacitidine.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Triple-negative Breast Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment
    Arm Type
    Experimental
    Arm Description
    See Detailed Description
    Intervention Type
    Drug
    Intervention Name(s)
    azacitidine
    Other Intervention Name(s)
    5-AC, 5-azacytidine, azacytidine, Vidaza
    Intervention Description
    Given IV
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Intervention Type
    Other
    Intervention Name(s)
    immunohistochemistry staining method
    Other Intervention Name(s)
    immunohistochemistry
    Intervention Description
    Correlative studies
    Intervention Type
    Genetic
    Intervention Name(s)
    polymerase chain reaction
    Other Intervention Name(s)
    PCR
    Intervention Description
    Correlative studies
    Intervention Type
    Genetic
    Intervention Name(s)
    western blotting
    Other Intervention Name(s)
    Blotting, Western, Western Blot
    Intervention Description
    Correlative studies
    Intervention Type
    Genetic
    Intervention Name(s)
    nucleic acid sequencing
    Other Intervention Name(s)
    Gene Sequencing, Molecular Biology, Nucleic Acid Sequencing
    Intervention Description
    Correlative studies
    Intervention Type
    Procedure
    Intervention Name(s)
    therapeutic conventional surgery
    Intervention Description
    Undergo definitive breast surgery
    Primary Outcome Measure Information:
    Title
    Percent of participants with ER/PR response after receiving 10 doses of 5-Azacitidine
    Time Frame
    6 months after enrollment of last patient

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Resectable tumor measuring 2 cm or more Histologically documented triple negative invasive breast cancer characterized by 0% Immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for PR-alpha, and no amplification of HER2/neu by fluorescence in situ hybridization (FISH); standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and PR-beta Southwest Oncology Group (SWOG) performance status of less than or equal to 1 Absolute neutrophil count (ANC) >= 1500/μL Hemoglobin (Hgb) >= 9 g/dL Platelets >= 100,000/uL Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x upper limit normal (ULN) or =< 5.0 x ULN in patients with liver metastases Creatinine =< 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN) Phosphorous >= LLN Calcium >= LLN Magnesium > LLN Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment Accessible for treatment and follow-up Written informed consent prior to study entry Exclusion Criteria: HER2/neu amplification by FISH Concurrent neoadjuvant treatment with chemotherapy, endocrine therapy, or radiotherapy Known hypersensitivity to azacitidine or mannitol Preexisting hepatic impairment or renal impairment Intent to receive additional neoadjuvant therapy prior to surgery Concurrent use of an histone deacetylase (HDAC) inhibitor or hydralazine Known diagnosis of human immunodeficiency virus (HIV) infection Major surgery < 4 weeks prior to starting study drug Pregnant or breastfeeding or female of reproductive potential not using an effective method of birth control Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase inhibitors) within 6 months of study entry Underlying medical, psychiatric or social conditions that would preclude patient from receiving treatment
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Agustin Garcia, MD
    Organizational Affiliation
    University of Southern California
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

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