<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01695057</url>
  </required_header>
  <id_info>
    <org_study_id>1B-10-10</org_study_id>
    <secondary_id>NCI-2012-01612</secondary_id>
    <nct_id>NCT01695057</nct_id>
  </id_info>
  <brief_title>Vorinostat Before Surgery in Treating Patients With Triple-Negative Breast Cancer</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies vorinostat before surgery in treating patients with&#xD;
      triple-negative breast cancer. Vorinostat may stop the growth of tumor cells by blocking some&#xD;
      of the enzymes needed for cell growth. Giving enzyme inhibitor therapy before surgery may&#xD;
      make the tumor smaller and reduce the amount of normal tissue that needs to be removed&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the ability of histone deacetylase (HDAC) inhibition using suberoylanilide&#xD;
      hydroxamic acid (SAHA) (vorinostat) to induce expression of the estrogen receptor (ER) and&#xD;
      progesterone receptor (PR) genes in solid human triple negative invasive breast cancer.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive vorinostat 400 mg daily orally (PO) on days 1-21 followed by surgery within&#xD;
      14 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">October 2015</completion_date>
  <primary_completion_date type="Anticipated">October 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Combined PR/ER response</measure>
    <time_frame>21 days</time_frame>
    <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 McNamaraÃ¢s 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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>Within 3 days prior to surgery</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Stage II Breast Cancer</condition>
  <condition>Stage IIIA Breast Cancer</condition>
  <condition>Triple-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (vorinostat and surgery)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vorinostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (vorinostat and surgery)</arm_group_label>
    <other_name>L-001079038</other_name>
    <other_name>SAHA</other_name>
    <other_name>suberoylanilide hydroxamic acid</other_name>
    <other_name>Zolinza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>therapeutic conventional surgery</intervention_name>
    <description>Undergo surgery</description>
    <arm_group_label>Treatment (vorinostat and surgery)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (vorinostat and surgery)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Resectable tumor measuring 2cm or more&#xD;
&#xD;
          -  Histologically documented, newly diagnosed, triple negative invasive breast cancer&#xD;
             characterized by 0% immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC&#xD;
             nuclear staining for PR-alpha, and no amplification of human epidermal growth factor&#xD;
             receptor 2 (HER2)/neu by fluorescent in situ hybridization (FISH) using institutional&#xD;
             standard; standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha&#xD;
             and PR-beta&#xD;
&#xD;
          -  Southwest Oncology Group (SWOG) performance status of less than or equal to 1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/uL&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 9 g/dL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and&#xD;
             alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =&lt; 2.5 x&#xD;
             upper limit of normal (ULN) or =&lt; 5.0 x ULN in patients with liver metastases&#xD;
&#xD;
          -  Creatinine =&lt; 2.0 mg/dL or calculated creatinine clearance &gt;= 50 ml/min&#xD;
&#xD;
          -  Albumin &gt;= 3 g/dL&#xD;
&#xD;
          -  Potassium &gt;= lower limit normal (LLN)&#xD;
&#xD;
          -  Phosphorous &gt;= LLN&#xD;
&#xD;
          -  Calcium &gt;= LLN&#xD;
&#xD;
          -  Magnesium &gt; LLN&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             performed within 7 days prior to start of treatment&#xD;
&#xD;
          -  Accessible for treatment and follow-up&#xD;
&#xD;
          -  Written informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HER2/neu amplification by FISH&#xD;
&#xD;
          -  Concurrent neoadjuvant anti-cancer treatment with chemotherapy, endocrine therapy,&#xD;
             biologically targeted therapy or radiotherapy&#xD;
&#xD;
          -  Known hypersensitivity to SAHA&#xD;
&#xD;
          -  Preexisting hepatic impairment or renal impairment&#xD;
&#xD;
          -  Intent to receive additional neoadjuvant therapy prior to surgery&#xD;
&#xD;
          -  Concurrent use of an HDAC inhibitor or hydralazine&#xD;
&#xD;
          -  Known diagnosis of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Major surgery &lt; 4 weeks prior to starting study drug&#xD;
&#xD;
          -  Pregnant or breastfeeding or female of reproductive potential not using an effective&#xD;
             method of birth control&#xD;
&#xD;
          -  Other concurrent severe, uncontrolled infection or intercurrent illness, including but&#xD;
             not limited to ongoing or active infection or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements&#xD;
&#xD;
          -  Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase&#xD;
             inhibitors) within 6 months of study entry&#xD;
&#xD;
          -  Underlying medical, psychiatric or social conditions that would preclude patient from&#xD;
             receiving treatment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Agustin Garcia</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>January 27, 2014</last_update_submitted>
  <last_update_submitted_qc>January 27, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 28, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vorinostat</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01695057
org study id: 1B-10-10
secondary id: NCI-2012-01612
nct id: NCT01695057
lead sponsor: 
collaborator: 
has dmc: Yes
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
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Combined PR/ER response
time frame: 21 days
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 McNamaraÃ¢s 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.
measure: Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: Within 3 days prior to surgery
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.
arm group label: Treatment (vorinostat and surgery)
arm group type: Experimental
description: Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
intervention type: Drug
intervention name: vorinostat
description: Given PO
arm group label: Treatment (vorinostat and surgery)
other name: L-001079038
other name: SAHA
other name: suberoylanilide hydroxamic acid
other name: Zolinza
intervention type: Procedure
intervention name: therapeutic conventional surgery
description: Undergo surgery
arm group label: Treatment (vorinostat and surgery)
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (vorinostat and surgery)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Agustin Garcia
role: Principal Investigator
affiliation: University of Southern California
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Vorinostat