<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/NCT02206984</url>
  </required_header>
  <id_info>
    <org_study_id>13-164 (ILC)</org_study_id>
    <nct_id>NCT02206984</nct_id>
  </id_info>
  <brief_title>Endocrine Response in Women With Invasive Lobular Breast Cancer</brief_title>
  <official_title>A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Priscilla McAuliffe</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      RATIONALE: Currently, adjuvant endocrine therapy often follows a &quot;one-size-fits- all&quot;&#xD;
      approach, with most premenopausal women receiving tamoxifen, and most postmenopausal&#xD;
      receiving aromatase inhibitor therapy. In current clinical practice, patients with invasive&#xD;
      lobular carcinoma are treated no differently than patients with invasive ductal carcinoma&#xD;
      based on the void of information specific to patients with this tumor type. Identification of&#xD;
      a biological signal of tamoxifen and/or AI-resistance and/or fulvestrant-sensitivity in ILC&#xD;
      patients would have dramatic implications for the future management of this breast cancer&#xD;
      subtype.&#xD;
&#xD;
      PURPOSE: To study whether fulvestrant is more effective than anastrozole or tamoxifen in&#xD;
      reducing Ki67 in ILC and whether that Ki67 reduction will correlate with alterations in&#xD;
      expression of ER and ER-regulated genes. Differential Ki67 effect in this study will serve as&#xD;
      a surrogate for outcome of ILC patients on endocrine therapy.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To determine the change from baseline to post-treatment Ki67 values in ER-positive,&#xD;
      HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or&#xD;
      further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine&#xD;
      treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given&#xD;
      orally daily), or tamoxifen (20mg given orally daily).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES&#xD;
&#xD;
      Primary&#xD;
&#xD;
      To determine the change from baseline to post-treatment Ki67 values in ER-positive,&#xD;
      HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or&#xD;
      further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine&#xD;
      treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given&#xD;
      orally daily), or tamoxifen (20mg given orally daily).&#xD;
&#xD;
      Secondary&#xD;
&#xD;
        -  To evaluate ER protein expression in ILC tissues at baseline and following neoadjuvant&#xD;
           endocrine therapy.&#xD;
&#xD;
        -  To evaluate PR protein expression in ILC tissues at baseline and following neo-adjuvant&#xD;
           endocrine therapy.&#xD;
&#xD;
        -  To evaluate ER-related and ILC-specific candidate gene mRNA expression in ILC tissues at&#xD;
           baseline and following neoadjuvant endocrine therapy in an effort to identify biomarkers&#xD;
           of endocrine response and putative drivers of endocrine resistance in ILC.&#xD;
&#xD;
        -  To evaluate associations between changes in Ki67 in ILC tissues following neoadjuvant&#xD;
           endocrine therapy with ER and PR protein expression, or ER and candidate gene mRNA&#xD;
           expression at baseline and post-treatment.&#xD;
&#xD;
      Exploratory&#xD;
&#xD;
        -  To evaluate DNA methylation in ILC tissues at baseline and following neo-adjuvant&#xD;
           endocrine therapy.&#xD;
&#xD;
        -  To evaluate associations between germline and somatic DNA sequence variants with changes&#xD;
           in Ki67 in ILC tissues following neo-adjuvant endocrine therapy.&#xD;
&#xD;
        -  To evaluate the activity of signaling pathways in ILC tissues by immunohistochemical or&#xD;
           other protein analyses, such as histone modifications, at baseline and following&#xD;
           neo-adjuvant endocrine therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 30, 2015</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Ki67 proliferative index</measure>
    <time_frame>Baseline (prior to treatment) to Day 21-24</time_frame>
    <description>Ki67 proliferative index is measured as the percent of positively staining cells. As a proliferation marker to measure the growth fraction of cells in human tumors, the expression of Ki67 is strongly associated with cell proliferation and used in routine pathology. pKi67 is well characterized at the molecular level and extensively used as a prognostic and predictive marker in cancer. Index values will be log- transformed (Ki67Day 21/Ki67BL).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Estrogen receptor (ER) protein expression</measure>
    <time_frame>Baseline (prior to treatment) to Day 21-24</time_frame>
    <description>ER protein expression in Invasive lobular carcinoma (ILC) tissues will be measured as the percent of positively staining cells. ER protein is a biomarker of endocrine response to estrogen receptor inhibiting/blocking treatment. ILC tumors can contain high amounts of estrogen receptors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estrogen receptor (ER) related gene expression</measure>
    <time_frame>Baseline (prior to treatment) to Day 21-24</time_frame>
    <description>Invasive lobular carcinoma (ILC)-specific target gene mRNA expression in tissues will be measured will be measured as the percent of positively staining cells.in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance. ILC tumors can contain increased amounts of estrogen receptors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ki67</measure>
    <time_frame>Baseline (prior to treatment) to Day 21-24</time_frame>
    <description>Ki67 marker in tissues will be measured as the percent of positively staining cells. Ki67 is strongly associated with cell proliferation and is widely used in routine pathology as a prognostic and predictive marker in cancer. The presence of Ki67 is associated with aggressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progesterone receptor (PR) protein expression</measure>
    <time_frame>Baseline (prior to treatment) to Day 21-24</time_frame>
    <description>Invasive lobular carcinoma (ILC)-specific target gene mRNA expression in tissues will be measured will be measured as the percent of positively staining cells to identify biomarkers of endocrine response and putative drivers of endocrine resistance. ILC tumors can contain increased amounts of progesterone receptors.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">201</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>tamoxifen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tamoxifen is administered orally, at a dose of 20 mg,daily, for 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anastrozole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1mg given orally daily for 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>fulvestrant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>500 mg, administered as two 250 mg IM injections, given on days 1 and 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <arm_group_label>tamoxifen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <arm_group_label>Anastrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant</intervention_name>
    <arm_group_label>fulvestrant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed invasive lobular breast cancer, that is hormone&#xD;
             receptor-positive and HER2-negative, measuring at least 1 centimeter (cm)&#xD;
             radiographically or clinically, clinical stages I-III. Invasive lobular histology will&#xD;
             be diagnosed at the enrolling institution for purposes of study participation.&#xD;
             Subsequently, invasive lobular histology will be confirmed by central pathology&#xD;
             review, but this central review will not be required prior to patient enrollment.&#xD;
&#xD;
          -  Prior to initiation of study agents, study participants will be highly encouraged to&#xD;
             undergo a baseline research core biopsy of their breast tumor. If this is not possible&#xD;
             or the patient refuses, the pre-treatment tumor sample must be obtained from their&#xD;
             archival diagnostic core biopsy. If definitive surgery is not performed at day 21-27&#xD;
             after study treatment, a second post-treatment research core biopsy will need to be&#xD;
             obtained from their breast tumor. For patients undergoing surgery, the second biopsy&#xD;
             will be removed from the breast tumor tissue excised during their operation. Note: In&#xD;
             the event that the baseline breast tumor biopsy performed for research purposes does&#xD;
             not yield adequate tumor tissue for analysis of the primary and secondary endpoints,&#xD;
             tissue will be requested from the patient's archival clinical diagnostic core biopsy&#xD;
             if it is available.The patient will still remain on study and complete protocol&#xD;
             therapy as planned in this unlikely event.&#xD;
&#xD;
          -  Hormone receptor (HR) status of the invasive component must be documented before trial&#xD;
             enrollment. The tumor must be HR-positive. HR will be considered positive if staining&#xD;
             is 1% or greater for ER and/or PR. This will be determined at the enrolling&#xD;
             institution for purposes of study participation and enrollment onto the trial.&#xD;
             Subsequently, HR status will be confirmed by central pathology review, but this&#xD;
             central review will not be required prior to enrolling the patient. HER2 status will&#xD;
             be determined locally only, based upon current ASCO/CAP guidelines.&#xD;
&#xD;
          -  Patients must be female.&#xD;
&#xD;
          -  Participants must be fully postmenopausal.&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2.&#xD;
&#xD;
          -  Adequate organ and marrow function as defined by a history and physical exam that&#xD;
             rules out comorbidities that would be exclusions to participation in the study (see&#xD;
             exclusion criteria) and clinical laboratory parameters as deemed clinically&#xD;
             appropriate by the treating physician.&#xD;
&#xD;
          -  Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen&#xD;
             and/or progestin), but must have been discontinued at least 30 days prior to the study&#xD;
             enrollment. Vaginal preparations (e.g., Vagifem® or Estring®)&#xD;
&#xD;
          -  Participant must be aware of the nature of her malignancy, understand the study&#xD;
             requirements and risks and be able and willing to sign a written informed consent&#xD;
             document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior or concurrent use of hormonal therapy, chemotherapy, radiation therapy, or novel&#xD;
             therapy to treat the current breast cancer, including any history of prior irradiation&#xD;
             to the ipsilateral breast. Additionally, the patient must not have had hormonal&#xD;
             therapy for breast cancer treatment or for breast cancer prevention within 2 years&#xD;
             prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral&#xD;
             breast cancer) at separate sites is permissible, provided the patient does not receive&#xD;
             medical treatments for breast cancer or radiation therapy to the ipsilateral breast&#xD;
             during the 21 day study intervention period.&#xD;
&#xD;
          -  Concurrent use of any other investigational agents.&#xD;
&#xD;
          -  History of allergic reactions/hypersensitivity attributed to compounds of similar&#xD;
             chemical or biologic composition to tamoxifen, anastrozole, or fulvestrant or any of&#xD;
             their ingredients.&#xD;
&#xD;
          -  History of thromboembolic disease or uterine cancer that is considered a&#xD;
             contraindication to tamoxifen.&#xD;
&#xD;
          -  Active hepatitis viral infections or a known history of liver disease, especially&#xD;
             moderate (Child-Pugh Class B) to severe (Child-Pugh Class C) hepatic impairment.&#xD;
&#xD;
          -  Uncontrolled current illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  HER-2 positivity.&#xD;
&#xD;
          -  Increased Risk of bleeding: including a history of a bleeding diathesis and/or known&#xD;
             history of severe thrombocytopenia. NOTE: Anticoagulant use is not a contraindication&#xD;
             to fulvestrant, but caution is advised in administration in patients on&#xD;
             anticoagulation. Patients on anticoagulation who will receive fulvestrant will have PT&#xD;
             and aPTT/INR assessed at baseline.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Priscilla McAuliffe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UPMC Magee Womens Hopspital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Josh L Plassmeyer, MSCR</last_name>
    <phone>14126486417</phone>
    <email>plassmeyerjm@upmc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rometa R Pollard, BS</last_name>
    <phone>412-641-5430</phone>
    <email>pollardrr@upmc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UAB Comprehensive Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erica M Reasor-Stringer, MD</last_name>
      <phone>205-934-3411</phone>
      <email>strinem@uab.edu</email>
    </contact>
    <contact_backup>
      <last_name>Liz Busby, RN, BSN</last_name>
      <phone>205-934-0337</phone>
      <email>lizbusby@uab.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>UCSF Helen Diller Family Comprehensive Cancer Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudine Isaacs, MD</last_name>
      <phone>202-444-2223</phone>
      <email>isaacsc@georgetown.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kerrie Bouker, Ph.D.</last_name>
      <phone>202-687-0114</phone>
      <email>briggsk@georgetown.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>IU Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tina Hieken, MD</last_name>
      <phone>855-776-0015</phone>
      <email>Hieken.Tina@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kim Hitchcock</last_name>
      <phone>507-266-3867</phone>
      <email>hitchcock.kim@mayo.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>ALBERT EINSTEIN COLLEGE OF MEDICINE Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph Sparano, MD</last_name>
      <phone>718-405-8404</phone>
      <email>JSPARANO@montefiore.org</email>
    </contact>
    <contact_backup>
      <last_name>Vilma Calderon, RN</last_name>
      <email>VCALDERO@montefiore.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristalyn Gallagher, DO</last_name>
      <phone>919-966-5221</phone>
      <email>kristalyn_gallagher@med.unc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Rachel Phipps, RN</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jami Rothman, MD</last_name>
      <phone>215-662-2552</phone>
      <email>jami.rothman@pennmedicine.upenn.edu</email>
    </contact>
    <contact_backup>
      <last_name>Sheryl Foster</last_name>
      <email>Sheryl.Foster@pennmedicine.upenn.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Josh Plassmeyer</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Josh L Plassmeyer, MSCR</last_name>
      <phone>412-648-6417</phone>
      <email>plassmeyerjm@upmc.edu</email>
    </contact>
    <investigator>
      <last_name>Priscilla McAuliffe, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lester and Sue Smith Breast Center, Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie Nangia, MD</last_name>
      <phone>713-798-6970</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77064</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Univ. of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hannah Linden, MD</last_name>
      <phone>206-288-1234</phone>
      <email>hmlinden@seattlecca.org</email>
    </contact>
    <contact_backup>
      <last_name>Obsy Tadesse</last_name>
      <phone>206-288-6831</phone>
      <email>otadesse@seattlecca.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>January 8, 2023</last_update_submitted>
  <last_update_submitted_qc>January 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Priscilla McAuliffe</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </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>Tamoxifen</mesh_term>
    <mesh_term>Fulvestrant</mesh_term>
    <mesh_term>Anastrozole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02206984
org study id: 13-164 (ILC)
nct id: NCT02206984
lead sponsor: 
has dmc: Yes
RATIONALE: Currently, adjuvant endocrine therapy often follows a "one-size-fits- all"
      approach, with most premenopausal women receiving tamoxifen, and most postmenopausal
      receiving aromatase inhibitor therapy. In current clinical practice, patients with invasive
      lobular carcinoma are treated no differently than patients with invasive ductal carcinoma
      based on the void of information specific to patients with this tumor type. Identification of
      a biological signal of tamoxifen and/or AI-resistance and/or fulvestrant-sensitivity in ILC
      patients would have dramatic implications for the future management of this breast cancer
      subtype.

      PURPOSE: To study whether fulvestrant is more effective than anastrozole or tamoxifen in
      reducing Ki67 in ILC and whether that Ki67 reduction will correlate with alterations in
      expression of ER and ER-regulated genes. Differential Ki67 effect in this study will serve as
      a surrogate for outcome of ILC patients on endocrine therapy.

      Primary Objective:

      To determine the change from baseline to post-treatment Ki67 values in ER-positive,
      HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or
      further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine
      treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given
      orally daily), or tamoxifen (20mg given orally daily).
OBJECTIVES

      Primary

      To determine the change from baseline to post-treatment Ki67 values in ER-positive,
      HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or
      further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine
      treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given
      orally daily), or tamoxifen (20mg given orally daily).

      Secondary

        -  To evaluate ER protein expression in ILC tissues at baseline and following neoadjuvant
           endocrine therapy.

        -  To evaluate PR protein expression in ILC tissues at baseline and following neo-adjuvant
           endocrine therapy.

        -  To evaluate ER-related and ILC-specific candidate gene mRNA expression in ILC tissues at
           baseline and following neoadjuvant endocrine therapy in an effort to identify biomarkers
           of endocrine response and putative drivers of endocrine resistance in ILC.

        -  To evaluate associations between changes in Ki67 in ILC tissues following neoadjuvant
           endocrine therapy with ER and PR protein expression, or ER and candidate gene mRNA
           expression at baseline and post-treatment.

      Exploratory

        -  To evaluate DNA methylation in ILC tissues at baseline and following neo-adjuvant
           endocrine therapy.

        -  To evaluate associations between germline and somatic DNA sequence variants with changes
           in Ki67 in ILC tissues following neo-adjuvant endocrine therapy.

        -  To evaluate the activity of signaling pathways in ILC tissues by immunohistochemical or
           other protein analyses, such as histone modifications, at baseline and following
           neo-adjuvant endocrine therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Ki67 proliferative index
time frame: Baseline (prior to treatment) to Day 21-24
description: Ki67 proliferative index is measured as the percent of positively staining cells. As a proliferation marker to measure the growth fraction of cells in human tumors, the expression of Ki67 is strongly associated with cell proliferation and used in routine pathology. pKi67 is well characterized at the molecular level and extensively used as a prognostic and predictive marker in cancer. Index values will be log- transformed (Ki67Day 21/Ki67BL).
measure: Estrogen receptor (ER) protein expression
time frame: Baseline (prior to treatment) to Day 21-24
description: ER protein expression in Invasive lobular carcinoma (ILC) tissues will be measured as the percent of positively staining cells. ER protein is a biomarker of endocrine response to estrogen receptor inhibiting/blocking treatment. ILC tumors can contain high amounts of estrogen receptors.
measure: Estrogen receptor (ER) related gene expression
time frame: Baseline (prior to treatment) to Day 21-24
description: Invasive lobular carcinoma (ILC)-specific target gene mRNA expression in tissues will be measured will be measured as the percent of positively staining cells.in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance. ILC tumors can contain increased amounts of estrogen receptors.
measure: Change in Ki67
time frame: Baseline (prior to treatment) to Day 21-24
description: Ki67 marker in tissues will be measured as the percent of positively staining cells. Ki67 is strongly associated with cell proliferation and is widely used in routine pathology as a prognostic and predictive marker in cancer. The presence of Ki67 is associated with aggressive disease.
measure: Progesterone receptor (PR) protein expression
time frame: Baseline (prior to treatment) to Day 21-24
description: Invasive lobular carcinoma (ILC)-specific target gene mRNA expression in tissues will be measured will be measured as the percent of positively staining cells to identify biomarkers of endocrine response and putative drivers of endocrine resistance. ILC tumors can contain increased amounts of progesterone receptors.
arm group label: tamoxifen
arm group type: Active Comparator
description: Tamoxifen is administered orally, at a dose of 20 mg,daily, for 21 days
arm group label: Anastrozole
arm group type: Active Comparator
description: 1mg given orally daily for 21 days
arm group label: fulvestrant
arm group type: Active Comparator
description: 500 mg, administered as two 250 mg IM injections, given on days 1 and 14
intervention type: Drug
intervention name: Tamoxifen
arm group label: tamoxifen
intervention type: Drug
intervention name: Anastrozole
arm group label: Anastrozole
intervention type: Drug
intervention name: Fulvestrant
arm group label: fulvestrant
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Priscilla McAuliffe, MD
role: Principal Investigator
affiliation: UPMC Magee Womens Hopspital
last name: Josh L Plassmeyer, MSCR
phone: 14126486417
email: plassmeyerjm@upmc.edu
last name: Rometa R Pollard, BS
phone: 412-641-5430
email: pollardrr@upmc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Priscilla McAuliffe
investigator title: M.D.
mesh term: Breast Neoplasms
mesh term: Tamoxifen
mesh term: Fulvestrant
mesh term: Anastrozole
sharing ipd: No