<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/NCT01730729</url>
  </required_header>
  <id_info>
    <org_study_id>NU 12B06</org_study_id>
    <secondary_id>NCI-2012-02039</secondary_id>
    <secondary_id>STU00071477</secondary_id>
    <nct_id>NCT01730729</nct_id>
  </id_info>
  <brief_title>Cabergoline in Metastatic Breast Cancer</brief_title>
  <official_title>A Pilot Phase II Trial of Cabergoline in the Treatment of Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lynn Sage Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prolactin is a hormone produced in the pituitary gland. Previous studies have revealed that&#xD;
      elevated levels of the hormone prolactin might be associated with an increased risk of breast&#xD;
      cancer. Cabergoline has been shown to lower prolactin levels in the blood.&#xD;
&#xD;
      The purpose of this study is to evaluate the effectiveness of cabergoline in treating&#xD;
      metastatic breast cancer disease in those who test positive for the prolactin receptor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate overall response rate (ORR) of cabergoline in women with metastatic breast&#xD;
      cancer.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate the progression-free survival (PFS) and overall survival (OS). II. Evaluate&#xD;
      toxicity. III. Correlate serum prolactin levels during therapy with response. IV. Evaluate&#xD;
      within-patient changes in computed tomography (CT) and bone scan measurements taken at&#xD;
      baseline and after 2 cycles of treatment.&#xD;
&#xD;
      V. Evaluate within-patient changes in prolactin receptor (PRLr) expression from baseline to&#xD;
      after 1 cycle of treatment in those patients who consent to optional repeat biopsy.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive cabergoline orally (PO) twice weekly for weeks 1-4. Courses repeat every 4&#xD;
      weeks in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and then every 6&#xD;
      months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 11, 2013</start_date>
  <completion_date type="Actual">October 27, 2017</completion_date>
  <primary_completion_date type="Actual">December 15, 2015</primary_completion_date>
  <phase>Early Phase 1</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>Overall Response Rate (ORR) at 2 Months</measure>
    <time_frame>After 8 weeks (2 cycles) of treament</time_frame>
    <description>Overall Response Rate (ORR) is defined as the number of patients that achieved Complete Response (CR) or Partial Response (PR) and will be assessed after 8 weeks (2 cycles) of therapy using CT scan images and RECIST guidelines.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From start of treatment until progression of disease or death</time_frame>
    <description>Progression Free Survival (PFS) will be measured from time of treatment initiation until first documentation of progression of disease or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Toxicity</measure>
    <time_frame>After every 4 weeks (1 cycle) during treatment for up to 20 cycles and 30 days post last treatment</time_frame>
    <description>Toxicity will be assessed at the beginning of each cycle (1 cycle equals 28 days) during treatment and 30 days post last treatment during treatment. Toxicity will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:&#xD;
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grades 1 through 4 adverse events that were determined to be at least possibly related to treatment are combined and reported below.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Within-patient Imaging Measurements at Baseline and After 2 Cycles</measure>
    <time_frame>At baseline and at 8 weeks</time_frame>
    <description>At baseline and after 2 cycles changes CT and bone scan measurements will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Prolactin Receptor Expression Measurements at Baseline and After 1 Cycle</measure>
    <time_frame>At baseline and after 4 weeks (1 cycle)</time_frame>
    <description>Evaluate prolactin expression in biopsy tissue taken at baseline and after 4 weeks (1 cycle) of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlate Tissue Prolactin Biomarkers With Response to Therapy</measure>
    <time_frame>At baseline</time_frame>
    <description>Baseline tumor tissue was analyzed for prolactin receptor (PRLr) expression and was provided with an IHC-based Allred score of 0 to 300 based on percentage intensity where lower scores indicate less PRLr expression and high scores indicate more PRLr expression. Only the malignant epithelium was scored. The score was correlated with best response of patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From the start of treatment until death from any cause. Median follow up time of 6.817 months (95%CI 0.22-26.18)</time_frame>
    <description>Overall Survival (OS) is defined from the first day of treatment until death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Recurrent Breast Cancer</condition>
  <condition>Stage IV Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (cabergoline)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cabergoline</intervention_name>
    <description>Given orally</description>
    <arm_group_label>Treatment (cabergoline)</arm_group_label>
    <other_name>Dostinex</other_name>
    <other_name>FCE 21336</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed metastatic breast cancer; tissue (a&#xD;
             minimum of 3 slides) from the most recent biopsy is required for review and&#xD;
             confirmation of eligibility; NOTE: material should ideally be from the metastatic&#xD;
             disease, however material from the primary tumor is acceptable if that is all that is&#xD;
             available&#xD;
&#xD;
          -  Patients must have stage IV breast cancer&#xD;
&#xD;
          -  Patients must have tumors (primary or metastatic) that stain positively for the&#xD;
             prolactin receptor&#xD;
&#xD;
          -  Patients may have measurable or evaluable disease&#xD;
&#xD;
               -  Measurable disease is defined as at least one lesion that can be accurately&#xD;
                  measured in at least one dimension (longest diameter to be recorded) as &gt; 20 mm&#xD;
                  with conventional techniques or as &gt; 10 mm with spiral CT scan&#xD;
&#xD;
               -  Evaluable disease is disease that does not meet the criteria for measurable&#xD;
                  disease; examples would include patients with effusions or bone-only disease&#xD;
&#xD;
          -  Women of childbearing potential must commit to the use of effective barrier&#xD;
             (non-hormonal) contraception while on study&#xD;
&#xD;
          -  Patients must have a life expectancy of greater than 12 weeks&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =&lt;&#xD;
             2&#xD;
&#xD;
          -  Patients may have had a prior diagnosis of cancer if it has been &gt; 5 years since their&#xD;
             last treatment&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/uL (microliter)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/uL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL&#xD;
&#xD;
          -  Child Pugh score =&lt; 10&#xD;
&#xD;
          -  Patients must be able to swallow and retain oral medication&#xD;
&#xD;
          -  All patients must have given signed, informed consent prior to registration on study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or lactating are not eligible for study treatment&#xD;
&#xD;
          -  Patients who are undergoing concomitant radiotherapy are NOT eligible for&#xD;
             participation&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents or concurrent anticancer&#xD;
             therapy are NOT eligible for participation; previous systemic treatment is allowed&#xD;
             with a 2 week washout period prior to registration&#xD;
&#xD;
          -  Patients who are taking any herbal (alternative) medicines are NOT eligible for&#xD;
             participation; patients must be off any such medications by the time of registration&#xD;
&#xD;
          -  Patients who are receiving concomitant D2-antagonists (such as phenothiazines,&#xD;
             butyrophenones, thioxanthenes, or metoclopramide) are NOT eligible for participation;&#xD;
             patients must be off any such medications by the time of registration&#xD;
&#xD;
          -  Patients with known brain metastases are NOT eligible for participation&#xD;
&#xD;
          -  Patients with any of the following conditions or complications are NOT eligible for&#xD;
             participation:&#xD;
&#xD;
               -  Uncontrolled hypertension&#xD;
&#xD;
               -  Known hypersensitivity to ergot derivatives&#xD;
&#xD;
               -  History of cardiac valvular disorders, as suggested by anatomical evidence of&#xD;
                  valvulopathy of any valve (to be determined by pre-treatment evaluation including&#xD;
                  echocardiographic demonstration of valve leaflet thickening, valve restriction,&#xD;
                  or mixed valve restriction-stenosis)&#xD;
&#xD;
               -  History of pulmonary, pericardial, cardiac valvular, or retroperitoneal fibrotic&#xD;
                  disorders&#xD;
&#xD;
               -  Gastrointestinal (GI) tract disease resulting in an inability to take oral&#xD;
                  medication&#xD;
&#xD;
               -  Malabsorption syndrome&#xD;
&#xD;
               -  Require intravenous (IV) alimentation&#xD;
&#xD;
               -  History of prior surgical procedures affecting absorption&#xD;
&#xD;
               -  Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)&#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>Virginia Kaklamani</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <results_first_submitted>December 11, 2018</results_first_submitted>
  <results_first_submitted_qc>March 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 26, 2019</results_first_posted>
  <last_update_submitted>September 4, 2019</last_update_submitted>
  <last_update_submitted_qc>September 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2019</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cabergoline</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study opened for accrual on November 29, 2012 with an accrual goal of up to 20 patients. The first patient starting treatment February 11, 2013. Accrual was suspended twice during the study; May 28 2014 reopening June 11, 2014 and July 24 2015, reopening August 27 2015. The study was closed October 21, 2015 with 20 patients enrolled.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Cabergoline)</title>
          <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed 2 Cycles/Reached 1st Response</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated Cycle 3 and Beyond</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Cabergoline)</title>
          <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </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="12"/>
                  </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="20"/>
                  </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>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) at 2 Months</title>
        <description>Overall Response Rate (ORR) is defined as the number of patients that achieved Complete Response (CR) or Partial Response (PR) and will be assessed after 8 weeks (2 cycles) of therapy using CT scan images and RECIST guidelines.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
        <time_frame>After 8 weeks (2 cycles) of treament</time_frame>
        <population>2 patients did not reach 8 week response time point and were determined not to be evaluable for this objective.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) at 2 Months</title>
          <description>Overall Response Rate (ORR) is defined as the number of patients that achieved Complete Response (CR) or Partial Response (PR) and will be assessed after 8 weeks (2 cycles) of therapy using CT scan images and RECIST guidelines.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
          <population>2 patients did not reach 8 week response time point and were determined not to be evaluable for this objective.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>Progression Free Survival (PFS) will be measured from time of treatment initiation until first documentation of progression of disease or death from any cause.</description>
        <time_frame>From start of treatment until progression of disease or death</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>Progression Free Survival (PFS) will be measured from time of treatment initiation until first documentation of progression of disease or death from any cause.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.84" lower_limit="1.84" upper_limit="3.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Toxicity</title>
        <description>Toxicity will be assessed at the beginning of each cycle (1 cycle equals 28 days) during treatment and 30 days post last treatment during treatment. Toxicity will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:&#xD;
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grades 1 through 4 adverse events that were determined to be at least possibly related to treatment are combined and reported below.</description>
        <time_frame>After every 4 weeks (1 cycle) during treatment for up to 20 cycles and 30 days post last treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Toxicity</title>
          <description>Toxicity will be assessed at the beginning of each cycle (1 cycle equals 28 days) during treatment and 30 days post last treatment during treatment. Toxicity will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:&#xD;
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grades 1 through 4 adverse events that were determined to be at least possibly related to treatment are combined and reported below.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotansferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain in extremity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acute Kidney Injury</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotranserase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arthralgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dry eye</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperkalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypernatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypocalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Blood Cell decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Within-patient Imaging Measurements at Baseline and After 2 Cycles</title>
        <description>At baseline and after 2 cycles changes CT and bone scan measurements will be evaluated.</description>
        <time_frame>At baseline and at 8 weeks</time_frame>
        <population>This data was not collected and analysed as it was decided that it was not meaningful on its own.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Within-patient Imaging Measurements at Baseline and After 2 Cycles</title>
          <description>At baseline and after 2 cycles changes CT and bone scan measurements will be evaluated.</description>
          <population>This data was not collected and analysed as it was decided that it was not meaningful on its own.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Prolactin Receptor Expression Measurements at Baseline and After 1 Cycle</title>
        <description>Evaluate prolactin expression in biopsy tissue taken at baseline and after 4 weeks (1 cycle) of treatment.</description>
        <time_frame>At baseline and after 4 weeks (1 cycle)</time_frame>
        <population>No data collected as no patients completed repeat biopsy after 1 cycle of treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Prolactin Receptor Expression Measurements at Baseline and After 1 Cycle</title>
          <description>Evaluate prolactin expression in biopsy tissue taken at baseline and after 4 weeks (1 cycle) of treatment.</description>
          <population>No data collected as no patients completed repeat biopsy after 1 cycle of treatment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlate Tissue Prolactin Biomarkers With Response to Therapy</title>
        <description>Baseline tumor tissue was analyzed for prolactin receptor (PRLr) expression and was provided with an IHC-based Allred score of 0 to 300 based on percentage intensity where lower scores indicate less PRLr expression and high scores indicate more PRLr expression. Only the malignant epithelium was scored. The score was correlated with best response of patient.</description>
        <time_frame>At baseline</time_frame>
        <population>Only 9 patients had sufficient baseline tissue to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Correlate Tissue Prolactin Biomarkers With Response to Therapy</title>
          <description>Baseline tumor tissue was analyzed for prolactin receptor (PRLr) expression and was provided with an IHC-based Allred score of 0 to 300 based on percentage intensity where lower scores indicate less PRLr expression and high scores indicate more PRLr expression. Only the malignant epithelium was scored. The score was correlated with best response of patient.</description>
          <population>Only 9 patients had sufficient baseline tissue to be analyzed.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable Disease</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="170" lower_limit="110" upper_limit="220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="220" lower_limit="120" upper_limit="250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall Survival (OS) is defined from the first day of treatment until death from any cause.</description>
        <time_frame>From the start of treatment until death from any cause. Median follow up time of 6.817 months (95%CI 0.22-26.18)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall Survival (OS) is defined from the first day of treatment until death from any cause.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.41" lower_limit="7.06" upper_limit="NA">At the time of data collection cut off, not all patients were deceased and upper CI was not calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Clinical Benefit Rate (CBR) After 2 Cycles of Treatment</title>
        <description>Clinical Benefit Rate (CBR) is defined as the number of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and is assessed by RECIST guidelines for measurements of CT scan at 8 weeks (2 cycles) of treatment.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
        <time_frame>After 8 weeks (2 cycles) of treatment</time_frame>
        <population>2 patients did not reach the 8 week response assessment time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate (CBR) After 2 Cycles of Treatment</title>
          <description>Clinical Benefit Rate (CBR) is defined as the number of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and is assessed by RECIST guidelines for measurements of CT scan at 8 weeks (2 cycles) of treatment.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
          <population>2 patients did not reach the 8 week response assessment time point.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Disease Control at 12 Months</title>
        <description>Number of patients without progressive disease as assessed by CT scan and RECIST guidelines at 12 months of treatment.</description>
        <time_frame>At 12 months from start of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control at 12 Months</title>
          <description>Number of patients without progressive disease as assessed by CT scan and RECIST guidelines at 12 months of treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Best Overall Response</title>
        <description>Best Overall Response is defined as patients best response to treatment from treatment initiation until the end of treatment as assessed by RECIST guidelines of CT scans.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
        <time_frame>From the start of treatment until the end of treatment up to a maximum of 20 cycles (1 cycle = 4 weeks)</time_frame>
        <population>1 patient died on treatment 7 days after starting and was not included in this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response</title>
          <description>Best Overall Response is defined as patients best response to treatment from treatment initiation until the end of treatment as assessed by RECIST guidelines of CT scans.&#xD;
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.&#xD;
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started</description>
          <population>1 patient died on treatment 7 days after starting and was not included in this outcome measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Partial Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Change in Serum Prolactin Levels From Baseline and After 2 Cycles of Treatment</title>
        <description>Serum prolactin measurements were taken at baseline and after completion of two cycles of treatment. The mean drop was calculated for all patients, and for patients with best response of Stable Disease and Progressive Disease.</description>
        <time_frame>At baseline and after 2 cycles of treatment where 1 cycle =4 weeks</time_frame>
        <population>Serum prolactin at baseline and after 2 cycles of treatment were only available for 12 patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Cabergoline)</title>
            <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Prolactin Levels From Baseline and After 2 Cycles of Treatment</title>
          <description>Serum prolactin measurements were taken at baseline and after completion of two cycles of treatment. The mean drop was calculated for all patients, and for patients with best response of Stable Disease and Progressive Disease.</description>
          <population>Serum prolactin at baseline and after 2 cycles of treatment were only available for 12 patients.</population>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.425" lower_limit="-36.70" upper_limit="-0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.72" lower_limit="-11.50" upper_limit="-5.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.93" lower_limit="-36.70" upper_limit="-0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected over a 3 year period for the whole study. Patients were followed from treatment initiation, throughout treatment and 30 days post last treatment for up to 20 cycles (max number of cycles that any patient was treated) where 1 cycle equals 28 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Cabergoline)</title>
          <description>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
cabergoline: Given orally</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia (Hemoglobin decrease)</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oral Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood prolactin abnormal</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Cardiac troponin 1 increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Platelet Count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>White Blood Cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headaches</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <description>Low grade - Not resulting in hospitalization</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema Multiforme</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Erythematous papules</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Cesar Santa-Maria, MD</name_or_title>
      <organization>Northwestern University</organization>
      <phone>312-695-6180</phone>
      <email>cancertrials@northwestern.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/NCT01730729
org study id: NU 12B06
secondary id: NCI-2012-02039
secondary id: STU00071477
nct id: NCT01730729
lead sponsor: 
collaborator: 
has dmc: Yes
Prolactin is a hormone produced in the pituitary gland. Previous studies have revealed that
      elevated levels of the hormone prolactin might be associated with an increased risk of breast
      cancer. Cabergoline has been shown to lower prolactin levels in the blood.

      The purpose of this study is to evaluate the effectiveness of cabergoline in treating
      metastatic breast cancer disease in those who test positive for the prolactin receptor.
PRIMARY OBJECTIVES:

      I. To evaluate overall response rate (ORR) of cabergoline in women with metastatic breast
      cancer.

      SECONDARY OBJECTIVES:

      I. Evaluate the progression-free survival (PFS) and overall survival (OS). II. Evaluate
      toxicity. III. Correlate serum prolactin levels during therapy with response. IV. Evaluate
      within-patient changes in computed tomography (CT) and bone scan measurements taken at
      baseline and after 2 cycles of treatment.

      V. Evaluate within-patient changes in prolactin receptor (PRLr) expression from baseline to
      after 1 cycle of treatment in those patients who consent to optional repeat biopsy.

      OUTLINE:

      Patients receive cabergoline orally (PO) twice weekly for weeks 1-4. Courses repeat every 4
      weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 6
      months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) at 2 Months
time frame: After 8 weeks (2 cycles) of treament
description: Overall Response Rate (ORR) is defined as the number of patients that achieved Complete Response (CR) or Partial Response (PR) and will be assessed after 8 weeks (2 cycles) of therapy using CT scan images and RECIST guidelines.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.
Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started
measure: Progression Free Survival (PFS)
time frame: From start of treatment until progression of disease or death
description: Progression Free Survival (PFS) will be measured from time of treatment initiation until first documentation of progression of disease or death from any cause.
measure: Treatment Toxicity
time frame: After every 4 weeks (1 cycle) during treatment for up to 20 cycles and 30 days post last treatment
description: Toxicity will be assessed at the beginning of each cycle (1 cycle equals 28 days) during treatment and 30 days post last treatment during treatment. Toxicity will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grades 1 through 4 adverse events that were determined to be at least possibly related to treatment are combined and reported below.
measure: Change in Within-patient Imaging Measurements at Baseline and After 2 Cycles
time frame: At baseline and at 8 weeks
description: At baseline and after 2 cycles changes CT and bone scan measurements will be evaluated.
measure: Change in Prolactin Receptor Expression Measurements at Baseline and After 1 Cycle
time frame: At baseline and after 4 weeks (1 cycle)
description: Evaluate prolactin expression in biopsy tissue taken at baseline and after 4 weeks (1 cycle) of treatment.
measure: Correlate Tissue Prolactin Biomarkers With Response to Therapy
time frame: At baseline
description: Baseline tumor tissue was analyzed for prolactin receptor (PRLr) expression and was provided with an IHC-based Allred score of 0 to 300 based on percentage intensity where lower scores indicate less PRLr expression and high scores indicate more PRLr expression. Only the malignant epithelium was scored. The score was correlated with best response of patient.
measure: Overall Survival (OS)
time frame: From the start of treatment until death from any cause. Median follow up time of 6.817 months (95%CI 0.22-26.18)
description: Overall Survival (OS) is defined from the first day of treatment until death from any cause.
arm group label: Treatment (cabergoline)
arm group type: Experimental
description: Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: cabergoline
description: Given orally
arm group label: Treatment (cabergoline)
other name: Dostinex
other name: FCE 21336
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Virginia Kaklamani
role: Principal Investigator
affiliation: Northwestern University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Cabergoline
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 