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Vorinostat Before Surgery in Treating Patients With Triple-Negative Breast Cancer

Primary Purpose

Stage II Breast Cancer, Stage IIIA Breast Cancer, Triple-negative Breast Cancer

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
vorinostat
therapeutic conventional surgery
laboratory biomarker analysis
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage II Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Resectable tumor measuring 2cm or more
  • Histologically documented, newly diagnosed, 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 human epidermal growth factor receptor 2 (HER2)/neu by fluorescent in situ hybridization (FISH) using institutional standard; 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/uL
  • 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 of 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 anti-cancer treatment with chemotherapy, endocrine therapy, biologically targeted therapy or radiotherapy
  • Known hypersensitivity to SAHA
  • Preexisting hepatic impairment or renal impairment
  • Intent to receive additional neoadjuvant therapy prior to surgery
  • Concurrent use of an 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 (vorinostat and surgery)

    Arm Description

    Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.

    Outcomes

    Primary Outcome Measures

    Combined PR/ER response
    The proportion of patients who achieve sufficient deacetylation of ER and PR will be estimable with a standard error no greater than +/- 0.05. The proportion of patients who exhibit a sufficient change in ER or PR expression can be estimated with similar precision. In addition, paired t-tests and McNamaraâs test will be used to evaluate whether the effect of vorinostat on deacetylation status or gene expression differs between ER or PR, and linear regression analysis will be used to evaluate the association between deacetylation changes and corresponding expression changes in ER and PR genes.

    Secondary Outcome Measures

    Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    The toxicities observed will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI Common Toxicity Criteria v4.0 and nadir or maximum values for the laboratory measures), time of onset (i.e. week of treatment), duration, and reversibility or outcome.

    Full Information

    First Posted
    September 24, 2012
    Last Updated
    January 27, 2014
    Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01695057
    Brief Title
    Vorinostat Before Surgery in Treating Patients With Triple-Negative Breast Cancer
    Official Title
    A Pilot Clinical Trial to Evaluate the Biological Activity of HDAC (Histone Deacetylase Transferases) Inhibition on ER and PR Expression in Triple Negative Invasive Breast Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funding
    Study Start Date
    October 2012 (undefined)
    Primary Completion Date
    October 2014 (Anticipated)
    Study Completion Date
    October 2015 (Anticipated)

    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 pilot clinical trial studies vorinostat before surgery in treating patients with triple-negative breast cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving enzyme inhibitor therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed
    Detailed Description
    PRIMARY OBJECTIVES: I. To evaluate the ability of histone deacetylase (HDAC) inhibition using suberoylanilide hydroxamic acid (SAHA) (vorinostat) to induce expression of the estrogen receptor (ER) and progesterone receptor (PR) genes in solid human triple negative invasive breast cancer. OUTLINE: Patients receive vorinostat 400 mg daily orally (PO) on days 1-21 followed by surgery within 14 days.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stage II Breast Cancer, Stage IIIA 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 (vorinostat and surgery)
    Arm Type
    Experimental
    Arm Description
    Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
    Intervention Type
    Drug
    Intervention Name(s)
    vorinostat
    Other Intervention Name(s)
    L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
    Intervention Description
    Given PO
    Intervention Type
    Procedure
    Intervention Name(s)
    therapeutic conventional surgery
    Intervention Description
    Undergo surgery
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Primary Outcome Measure Information:
    Title
    Combined PR/ER response
    Description
    The proportion of patients who achieve sufficient deacetylation of ER and PR will be estimable with a standard error no greater than +/- 0.05. The proportion of patients who exhibit a sufficient change in ER or PR expression can be estimated with similar precision. In addition, paired t-tests and McNamaraâs test will be used to evaluate whether the effect of vorinostat on deacetylation status or gene expression differs between ER or PR, and linear regression analysis will be used to evaluate the association between deacetylation changes and corresponding expression changes in ER and PR genes.
    Time Frame
    21 days
    Secondary Outcome Measure Information:
    Title
    Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    Description
    The toxicities observed will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI Common Toxicity Criteria v4.0 and nadir or maximum values for the laboratory measures), time of onset (i.e. week of treatment), duration, and reversibility or outcome.
    Time Frame
    Within 3 days prior to surgery

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Resectable tumor measuring 2cm or more Histologically documented, newly diagnosed, 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 human epidermal growth factor receptor 2 (HER2)/neu by fluorescent in situ hybridization (FISH) using institutional standard; 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/uL 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 of 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 anti-cancer treatment with chemotherapy, endocrine therapy, biologically targeted therapy or radiotherapy Known hypersensitivity to SAHA Preexisting hepatic impairment or renal impairment Intent to receive additional neoadjuvant therapy prior to surgery Concurrent use of an 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
    Organizational Affiliation
    University of Southern California
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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