<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/NCT01720602</url>
  </required_header>
  <id_info>
    <org_study_id>7841</org_study_id>
    <secondary_id>NCI-2012-02004</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT01720602</nct_id>
  </id_info>
  <brief_title>Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Hormone Therapy</brief_title>
  <official_title>A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy Part B</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</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 Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer&#xD;
      receiving hormone therapy. Vorinostat may help hormone therapy work better by making tumor&#xD;
      cells more sensitive to the drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Estimate the rate of clinical benefit (objective response plus stable disease) for&#xD;
      patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day&#xD;
      1-21) concurrent with daily aromatase inhibitor (AI) therapy (all 28 days).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess the safety and tolerability of vorinostat and AI combination therapy in patients&#xD;
      with metastatic breast cancer.&#xD;
&#xD;
      II. Assess the change in estrogen receptor (ER) expression, measured as the change in F-18 16&#xD;
      alpha-fluoroestradiol (FES) standardized uptake value (SUV) using FES positron emission&#xD;
      tomography (PET) completed per protocol 7184 after two weeks of vorinostat and AI therapy and&#xD;
      after 8 weeks of therapy.&#xD;
&#xD;
      III. Assess tumor metabolic response, measured as the change in fludeoxyglucose F 18 (FDG)&#xD;
      SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat and AI therapy&#xD;
      and after 8 weeks of therapy.&#xD;
&#xD;
      IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone&#xD;
      [FSH], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy.&#xD;
&#xD;
      V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor&#xD;
      receptor 2 (HER2), androgen receptor (AR), epidermal growth factor receptor (EGFR), vascular&#xD;
      endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat and AI&#xD;
      therapy in patients that consent to optional tissue biopsy procedure.&#xD;
&#xD;
      VI. Assess the time to progression and the overall survival of patients treated with 28-day&#xD;
      cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily&#xD;
      AI therapy (all 28 days).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive vorinostat orally (PO) 5 days a week for 3 weeks. Patients also receive AI&#xD;
      therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily&#xD;
      for 4 weeks. Courses repeat every 28 days in the absence of disease progression and&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years,&#xD;
      then every 6 months until progression, and then annually thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">January 2020</completion_date>
  <primary_completion_date type="Actual">March 2015</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>Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST</measure>
    <time_frame>8 weeks</time_frame>
    <description>A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response Rate According to RECIST</measure>
    <time_frame>8 weeks</time_frame>
    <description>A 90% score (Wilson) confidence interval will be computed for the response rate.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Duration of response will be summarized for responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From the time of start of study therapy to documented progression - up to 5 years</time_frame>
    <description>Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From the time of start of study therapy to date of documented death</time_frame>
    <description>Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Male Breast Cancer</condition>
  <condition>Recurrent Breast Cancer</condition>
  <condition>Stage IV Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vorinostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</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>Drug</intervention_type>
    <intervention_name>anastrozole</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>ANAS</other_name>
    <other_name>Arimidex</other_name>
    <other_name>ICI-D1033</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>letrozole</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>CGS 20267</other_name>
    <other_name>Femara</other_name>
    <other_name>LTZ</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>exemestane</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>Aromasin</other_name>
    <other_name>FCE-24304</other_name>
    <other_name>PNU 155971</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>positron emission tomography</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>FDG-PET</other_name>
    <other_name>PET</other_name>
    <other_name>PET scan</other_name>
    <other_name>tomography, emission computed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>F-18 16 alpha-fluoroestradiol</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>F-18 FES</other_name>
    <other_name>fluorine-18 16 alpha-fluoroestradiol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>fludeoxyglucose F 18</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
    <other_name>18FDG</other_name>
    <other_name>FDG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (vorinostat, AI therapy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically proven diagnosis of breast cancer&#xD;
&#xD;
          -  Stage IV disease&#xD;
&#xD;
          -  Patient has previously derived clinical benefit from endocrine therapy, but is no&#xD;
             longer deriving benefit to endocrine therapy in the opinion of the treating&#xD;
             investigator&#xD;
&#xD;
          -  At least one site of measurable disease, as defined by the modified Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) criteria&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Female patient is post menopausal as defined by one of the following; free from menses&#xD;
             for &gt;= 2 years, surgically sterilized, FSH and estradiol in post-menopausal range AND&#xD;
             surgical absence of uterus OR chemotherapy induced amenorrhea lasting &gt; 1 year OR&#xD;
             currently on ovarian suppression&#xD;
&#xD;
          -  Female patient of childbearing potential has a negative urine or serum (beta human&#xD;
             chorionic gonadotropin [B-hCG]) pregnancy test within 14 days prior to receiving the&#xD;
             first dose of vorinostat&#xD;
&#xD;
          -  Male patient agrees to use two barrier methods of contraception or abstain from&#xD;
             intercourse for the duration of the study&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 50,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Prothrombin time or international normalized ratio (INR) =&lt; 1.5 x upper limit of&#xD;
             normal (ULN) unless receiving therapeutic anticoagulation&#xD;
&#xD;
          -  Partial thromboplastin time (PTT) =&lt; 1.2 times the ULN unless the patient is receiving&#xD;
             therapeutic anticoagulation&#xD;
&#xD;
          -  Potassium (K) levels normal limits&#xD;
&#xD;
          -  Magnesium (Mg) levels normal limits&#xD;
&#xD;
          -  Calculated creatinine clearance &gt;= 30 mL/min&#xD;
&#xD;
               -  Creatinine clearance should be calculated per institutional standard&#xD;
&#xD;
          -  Serum total bilirubin =&lt; 1.5 x ULN&#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;
             ULN&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 2.5 x ULN&#xD;
&#xD;
          -  Patient, or the patient's legal representative, has voluntarily agreed to participate&#xD;
             by giving written informed consent&#xD;
&#xD;
          -  Patient has a life expectancy of at least 12 weeks in the opinion of the treating&#xD;
             investigator&#xD;
&#xD;
          -  Patient is willing to continue on same AI therapy&#xD;
&#xD;
          -  Patient agrees to participate in imaging protocol 7184 and is separately consented&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient has not derived clinical benefit from prior endocrine therapy&#xD;
&#xD;
          -  Patient is currently participating or has participated in a study with an&#xD;
             investigational compound or device within 30 days of initial dosing with study drug(s)&#xD;
             other than the imaging protocol 7184&#xD;
&#xD;
          -  Patient has received an ER blocking therapy (selective estrogen receptor modulating or&#xD;
             downregulating selective estrogen receptor modulator [SERM] or selective estrogen&#xD;
             receptor degrader [SERD] i.e. tamoxifen or fulvestrant) within the past 6 weeks&#xD;
&#xD;
          -  Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g.,&#xD;
             romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589,&#xD;
             MGCD0103, CRA024781, etc); patients who have received compounds with HDAC&#xD;
             inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not&#xD;
             enroll in this study; patients who have received such compounds for other indications,&#xD;
             e.g. valproic acid for epilepsy, may enroll after a 30-day washout period&#xD;
&#xD;
          -  Patient is on any systemic steroids that have not been stabilized to the equivalent of&#xD;
             =&lt; 10 mg/day prednisone during the 30 days prior to the start of the study drugs&#xD;
&#xD;
          -  Patient has known hypersensitivity to the components of study drug or its analogs&#xD;
&#xD;
          -  Patients with uncontrolled brain metastases&#xD;
&#xD;
          -  New York Heart Association (NYHA) class III or IV congestive heart failure, myocardial&#xD;
             infarction within the previous 6 months, QTc &gt; 0.47 seconds, or uncontrolled&#xD;
             arrhythmia&#xD;
&#xD;
          -  Type I diabetes mellitus; patients with type II diabetes mellitus will be included as&#xD;
             long as their glucose can be controlled to under 200 mg/dL&#xD;
&#xD;
          -  Patient is pregnant or breast feeding, or expecting to conceive or father children&#xD;
             within the projected duration of the study&#xD;
&#xD;
          -  Patient with a &quot;currently active&quot; second malignancy, other than non-melanoma skin&#xD;
             cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not&#xD;
             considered to have a &quot;currently active&quot; malignancy if they have completed therapy for&#xD;
             a prior malignancy, are disease free from prior malignancies for &gt; 5 years or are&#xD;
             considered by their physician to be at less than 30% risk of relapse&#xD;
&#xD;
          -  Patients with known active viral hepatitis&#xD;
&#xD;
          -  Patient has a history or current evidence of any condition, therapy, or laboratory&#xD;
             (lab) abnormality that might confound the results of the study, interfere with the&#xD;
             patient's participation for the full duration of the study or is not in the best&#xD;
             interest of the patient to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hannah Linden</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <results_first_submitted>October 30, 2014</results_first_submitted>
  <results_first_submitted_qc>October 30, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 6, 2014</results_first_posted>
  <last_update_submitted>January 2, 2020</last_update_submitted>
  <last_update_submitted_qc>January 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2020</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>Breast Neoplasms, Male</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Anastrozole</mesh_term>
    <mesh_term>Vorinostat</mesh_term>
    <mesh_term>Exemestane</mesh_term>
    <mesh_term>Fluorodeoxyglucose F18</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Vorinostat, AI Therapy)</title>
          <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease on therapy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Vorinostat, AI Therapy)</title>
          <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST</title>
        <description>A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Vorinostat, AI Therapy)</title>
            <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST</title>
          <description>A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60" lower_limit="35" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Response Rate According to RECIST</title>
        <description>A 90% score (Wilson) confidence interval will be computed for the response rate.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Vorinostat, AI Therapy)</title>
            <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate According to RECIST</title>
          <description>A 90% score (Wilson) confidence interval will be computed for the response rate.&#xD;
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60" lower_limit="35" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Duration of response will be summarized for responders.</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Vorinostat, AI Therapy)</title>
            <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Duration of response will be summarized for responders.</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.6" lower_limit="24.9" upper_limit="91.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.</description>
        <time_frame>From the time of start of study therapy to documented progression - up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Vorinostat, AI Therapy)</title>
            <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="0" upper_limit="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.</description>
        <time_frame>From the time of start of study therapy to date of documented death</time_frame>
        <population>OS includes one patient still alive 55 months after starting study therapy</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Vorinostat, AI Therapy)</title>
            <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.</description>
          <population>OS includes one patient still alive 55 months after starting study therapy</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19" lower_limit="1" upper_limit="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Vorinostat, AI Therapy)</title>
          <description>Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.&#xD;
vorinostat: Given PO&#xD;
anastrozole: Given PO&#xD;
letrozole: Given PO&#xD;
exemestane: Given PO&#xD;
positron emission tomography: Correlative studies&#xD;
F-18 16 alpha-fluoroestradiol: Correlative studies&#xD;
fludeoxyglucose F 18: Correlative studies&#xD;
laboratory biomarker analysis: Correlative studies</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver failure</sub_title>
                <description>Unrelated to the study treatment</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <description>Unrelated to the study treatment</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <description>grade 2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>neutropenia</sub_title>
                <description>grade 3 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>vomiting</sub_title>
                <description>grade 2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <description>grade 3 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <description>grade 2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Rigors / chills</sub_title>
                <description>grade 2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle cramps</sub_title>
                <description>grade 2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>grade 3 (CTCAE v3.0) The relationship to vorinostat was unclear.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>decrease in glomerular filtration</sub_title>
                <description>grade 1 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>creatinine increase</sub_title>
                <description>grade 1-2 (CTCAE v3.0)</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Hannah Linden, MD</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-288-6989</phone>
      <email>hmlinden@u.washington.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01720602
org study id: 7841
secondary id: NCI-2012-02004
secondary id: P30CA015704
nct id: NCT01720602
lead sponsor: 
collaborator: 
has dmc: No
This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer
      receiving hormone therapy. Vorinostat may help hormone therapy work better by making tumor
      cells more sensitive to the drug.
PRIMARY OBJECTIVES:

      I. Estimate the rate of clinical benefit (objective response plus stable disease) for
      patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day
      1-21) concurrent with daily aromatase inhibitor (AI) therapy (all 28 days).

      SECONDARY OBJECTIVES:

      I. Assess the safety and tolerability of vorinostat and AI combination therapy in patients
      with metastatic breast cancer.

      II. Assess the change in estrogen receptor (ER) expression, measured as the change in F-18 16
      alpha-fluoroestradiol (FES) standardized uptake value (SUV) using FES positron emission
      tomography (PET) completed per protocol 7184 after two weeks of vorinostat and AI therapy and
      after 8 weeks of therapy.

      III. Assess tumor metabolic response, measured as the change in fludeoxyglucose F 18 (FDG)
      SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat and AI therapy
      and after 8 weeks of therapy.

      IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone
      [FSH], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy.

      V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor
      receptor 2 (HER2), androgen receptor (AR), epidermal growth factor receptor (EGFR), vascular
      endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat and AI
      therapy in patients that consent to optional tissue biopsy procedure.

      VI. Assess the time to progression and the overall survival of patients treated with 28-day
      cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily
      AI therapy (all 28 days).

      OUTLINE:

      Patients receive vorinostat orally (PO) 5 days a week for 3 weeks. Patients also receive AI
      therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily
      for 4 weeks. Courses repeat every 28 days in the absence of disease progression and
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      then every 6 months until progression, and then annually thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST
time frame: 8 weeks
description: A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
measure: Response Rate According to RECIST
time frame: 8 weeks
description: A 90% score (Wilson) confidence interval will be computed for the response rate.
Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
measure: Duration of Response
time frame: Up to 5 years
description: Duration of response will be summarized for responders.
measure: Progression-free Survival (PFS)
time frame: From the time of start of study therapy to documented progression - up to 5 years
description: Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.
measure: Overall Survival
time frame: From the time of start of study therapy to date of documented death
description: Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.
arm group label: Treatment (vorinostat, AI therapy)
arm group type: Experimental
description: Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
intervention type: Drug
intervention name: vorinostat
description: Given PO
arm group label: Treatment (vorinostat, AI therapy)
other name: L-001079038
other name: SAHA
other name: suberoylanilide hydroxamic acid
other name: Zolinza
intervention type: Drug
intervention name: anastrozole
description: Given PO
arm group label: Treatment (vorinostat, AI therapy)
other name: ANAS
other name: Arimidex
other name: ICI-D1033
intervention type: Drug
intervention name: letrozole
description: Given PO
arm group label: Treatment (vorinostat, AI therapy)
other name: CGS 20267
other name: Femara
other name: LTZ
intervention type: Drug
intervention name: exemestane
description: Given PO
arm group label: Treatment (vorinostat, AI therapy)
other name: Aromasin
other name: FCE-24304
other name: PNU 155971
intervention type: Procedure
intervention name: positron emission tomography
description: Correlative studies
arm group label: Treatment (vorinostat, AI therapy)
other name: FDG-PET
other name: PET
other name: PET scan
other name: tomography, emission computed
intervention type: Radiation
intervention name: F-18 16 alpha-fluoroestradiol
description: Correlative studies
arm group label: Treatment (vorinostat, AI therapy)
other name: F-18 FES
other name: fluorine-18 16 alpha-fluoroestradiol
intervention type: Radiation
intervention name: fludeoxyglucose F 18
description: Correlative studies
arm group label: Treatment (vorinostat, AI therapy)
other name: 18FDG
other name: FDG
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (vorinostat, AI therapy)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hannah Linden
role: Principal Investigator
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Breast Neoplasms, Male
mesh term: Letrozole
mesh term: Anastrozole
mesh term: Vorinostat
mesh term: Exemestane
mesh term: Fluorodeoxyglucose F18
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 