<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/NCT04432454</url>
  </required_header>
  <id_info>
    <org_study_id>SMX 20-001</org_study_id>
    <nct_id>NCT04432454</nct_id>
  </id_info>
  <brief_title>Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation</brief_title>
  <acronym>ELAINEII</acronym>
  <official_title>An Open-label, Multicenter Study Evaluating the Safety of Lasofoxifene in Combination With Abemaciclib for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2- Breast Cancer and Have an ESR1 Mutation ( ELAINEII )</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sermonix Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sermonix Pharmaceuticals Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multicenter, single-arm safety study evaluating the safety and&#xD;
      tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and&#xD;
      postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer who have&#xD;
      disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease&#xD;
      and have an ESR1 mutation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 29, 2020</start_date>
  <completion_date type="Anticipated">February 10, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 10, 2023</primary_completion_date>
  <phase>Phase 2</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>Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit.</measure>
    <time_frame>All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months.</time_frame>
    <description>AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>PFS is defined as the time from the date of entry into the study to the earliest date of first documented progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate (CBR)</measure>
    <time_frame>24 weeks or longer</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>DoR will be assessed up to 24 months.</time_frame>
    <description>DoR is from the date of first documented response (CR or PR) to the date of first documented progression of disease or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response</measure>
    <time_frame>Time to response will be assessed up to 24 months.</time_frame>
    <description>From the date of entry into the study to the date of first documented response (CR or PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state pharmacokinetics (PK) sampling for lasofoxifene and abemaciclib concentrations as well as abemaciclib's 3 major metabolites</measure>
    <time_frame>Baseline and pre-dose at every visit starting at Visit 0 (Day 1) through Visit 4 (Week 8) and at the Final/ET visit if this occurred prior to Week 8</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women who have locally advanced or metastatic ER+/HER2- breast cancer and disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lasofoxifene and abemaciclib (VERZENIO (R)).</intervention_name>
    <description>Lasofoxifene 5 mg given once a day orally and abemaciclib 150 mg given twice a day orally.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pre- or postmenopausal.&#xD;
&#xD;
             Postmenopausal women are defined as:&#xD;
&#xD;
               1. ≥ 60 years of age with no vaginal bleeding over the prior year, or&#xD;
&#xD;
               2. &lt; 60 years with &quot;premature menopause&quot; or &quot;premature ovarian failure&quot; manifest&#xD;
                  itself with secondary amenorrhea for at least 1 year and follicle stimulating&#xD;
                  hormone (FSH) and estradiol levels in the postmenopausal range according to&#xD;
                  institutional standards, or&#xD;
&#xD;
               3. surgical menopause with bilateral oophorectomy. Note: Premenopausal women who&#xD;
                  meet all of the other entry criteria must be maintained on ovarian suppression&#xD;
                  (such as Lupron) during the study and subjects counseled to use appropriate&#xD;
                  contraception to prevent pregnancy.&#xD;
&#xD;
          2. If possible, a biopsy of metastatic breast cancer tissue should be obtained to provide&#xD;
             histological or cytological confirmation of ER+/HER2- disease as assessed by a local&#xD;
             laboratory, according to American Society of Clinical Oncology/College of American&#xD;
             Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a&#xD;
             biopsy is not possible, the ER and HER2 status from the tissue obtained at the time of&#xD;
             the original diagnosis must confirm that the subject is ER+ and HER2-.&#xD;
&#xD;
          3. Locally advanced and/or metastatic breast cancer with radiological or clinical&#xD;
             evidence of progression on the first or 2nd lines of hormonal therapy for metastatic&#xD;
             disease. Progression may have occurred on no more than 2 of the following endocrine&#xD;
             treatments for metastatic breast cancer: an aromatase inhibitor (AI) and/or&#xD;
             fulvestrant either as monotherapy or in combination with any commercially approved&#xD;
             CDKi; and/or the combination of fulvestrant and everolimus; and/or the combination of&#xD;
             fulvestrant and alpelisib; and/or tamoxifen; and/or the combination of&#xD;
             exemestane/everolimus. (Note: before starting study treatment, subjects should have&#xD;
             stopped any CDKi for at least 21 days)&#xD;
&#xD;
          4. Subjects must have had no evidence of progression for at least 6 months during their&#xD;
             first hormonal treatment for advanced breast cancer.&#xD;
&#xD;
          5. At least one or more of the following ESR1 point mutations as assessed in cell-free&#xD;
             circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C,&#xD;
             D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. Note: the&#xD;
             Sponsor's blood ctDNA assay must be used but tissue sequencing (if done) may be done&#xD;
             by a validated commercial laboratory.&#xD;
&#xD;
             Note: A positive ESR1 mutation in tissue or ctDNA using a validated commercial assay&#xD;
             if done prior or at the time of disease progression is acceptable to meet this entry&#xD;
             criteria. However, blood for ctDNA must still be obtained for genomic analyses using&#xD;
             the sponsor's ctDNA assay.&#xD;
&#xD;
          6. Locally advanced or metastatic breast cancer with either measurable (according to&#xD;
             RECIST 1.1) or non-measurable lesions.&#xD;
&#xD;
          7. Subjects may have received one cytotoxic chemotherapy regimen for metastatic disease&#xD;
             as well as those who received one cytotoxic chemotherapy regimen in the neo-adjuvant&#xD;
             or adjuvant setting prior to entry into the trial can be enrolled but must be free of&#xD;
             all chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy&#xD;
             before study entry. A washout period of at least 21 days is required between last&#xD;
             chemotherapy dose and entry into the study.&#xD;
&#xD;
          8. Stable breast cancer metastasis to the brain is allowed as long as the subject has&#xD;
             received radiotherapy and not demonstrated any evidence of brain metastasis&#xD;
             progression for at least 3 months after the completion of radiotherapy.&#xD;
&#xD;
          9. ECOG performance score of 0 or 1.&#xD;
&#xD;
         10. Adequate organ function as shown by:&#xD;
&#xD;
               1. absolute neutrophil count (ANC) ≥ 1,500 cells/mm3&#xD;
&#xD;
               2. platelet count ≥ 100,000 cells/mm3&#xD;
&#xD;
               3. hemoglobin ≥ 8.0 g/dl&#xD;
&#xD;
               4. ALT and AST levels ≤ 3 upper limit of normal (ULN) or ≤ 5 in the presence of&#xD;
                  liver metastasis&#xD;
&#xD;
               5. total serum bilirubin ≤ 1.5 X ULN (≤ 3 X ULN for subjects known to have Gilbert&#xD;
                  Syndrome)&#xD;
&#xD;
               6. alkaline phosphatase level ≤ 3 ULN&#xD;
&#xD;
               7. creatinine clearance of 40 ml/min or greater as calculated by the Cockcroft-Gault&#xD;
                  formula&#xD;
&#xD;
               8. International normalized ratio (INR) and activated partial thromboplastin (aPTT)&#xD;
                  &lt; 2.0 X ULN&#xD;
&#xD;
         11. Able to swallow tablets.&#xD;
&#xD;
         12. Able to understand and voluntarily sign a written informed consent before any&#xD;
             screening procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Lymphangitic carcinomatosis involving the lung.&#xD;
&#xD;
          2. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.&#xD;
&#xD;
          3. Radiotherapy within 30 days prior to entry into the study except in case of localized&#xD;
             radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which&#xD;
             can then be completed within 7 days prior to entry into the study. Subjects must have&#xD;
             recovered from radiotherapy toxicities prior to entry into the study.&#xD;
&#xD;
          4. Subjects with known inactivating RB1 mutations or deletions (Screening for RB1&#xD;
             mutation is not required for entry).&#xD;
&#xD;
          5. History of long QTC syndrome or a QTC of &gt; 480 msec.&#xD;
&#xD;
          6. History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6&#xD;
             months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance&#xD;
             are eligible as long as the DVT and/or PE occurred &gt; 6 months prior to enrollment and&#xD;
             there is no evidence for active thrombosis. The use of low-dose ASA is permitted.&#xD;
&#xD;
          7. Subjects on concomitant strong CYP3A4 inhibitors such as clarithromycin,&#xD;
             telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir,&#xD;
             indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.&#xD;
&#xD;
          8. Subjects on strong and moderate CYP3A4 inducers such as amprenavir, barbiturates,&#xD;
             carbamazepine, clotrimazole, dexamethasone, efavirenz, ethosuximide, griseofulvin,&#xD;
             modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, chronic prednisone&#xD;
             treatment, primidone, rifabutin, rifampin, rifapentine, ritonavir, topiramate.&#xD;
&#xD;
          9. Any significant co-morbidity that would impact the study or the subject's safety.&#xD;
             Since CDKi have reported the occurrence of interstitial lung disease (ILD), subjects&#xD;
             with a history of ILD and those with severe dyspnea at rest or requiring oxygen&#xD;
             therapy should not enter the study&#xD;
&#xD;
         10. Subject has an active systemic bacterial or fungal infection (requiring intravenous&#xD;
             [IV] antibiotics at the time of initiating study treatment).&#xD;
&#xD;
         11. History of a positive human immunodeficiency virus (HIV) or hepatitis B virus (HBV)&#xD;
             test. Screening is not required for enrollment.&#xD;
&#xD;
         12. Subjects with hepatitis C virus (HCV) at Screening who still have a viral load.&#xD;
             Subjects previously treated and achieved a HCV cure (no viral load) can be entered&#xD;
             into the study&#xD;
&#xD;
         13. History of malignancy within the past 5 years (excluding breast cancer), except basal&#xD;
             cell or squamous cell carcinoma of the skin curatively treated by surgery, or&#xD;
             early-stage cervical cancer.&#xD;
&#xD;
         14. Positive serum pregnancy test (only if premenopausal).&#xD;
&#xD;
         15. History of non-compliance to medical regimens.&#xD;
&#xD;
         16. Unwilling or unable to comply with the protocol.&#xD;
&#xD;
         17. Current participation in any clinical research trial involving an investigational drug&#xD;
             or device within the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham (UAB) - Comprehensive Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-3300</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yuma Regional Medical Center</name>
      <address>
        <city>Yuma</city>
        <state>Arizona</state>
        <zip>85364</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Cancer Care Med Group - Clinic Aid USA - Fountain Valley</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Health</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beacon Health System Memorial Regional Cancer Center</name>
      <address>
        <city>South Bend</city>
        <state>Indiana</state>
        <zip>46601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Jersey Cancer Care, PA</name>
      <address>
        <city>Belleville</city>
        <state>New Jersey</state>
        <zip>07109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-4009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Consultants, P.A.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology Oncology Associates of Fredericksburg</name>
      <address>
        <city>Fredericksburg</city>
        <state>Virginia</state>
        <zip>22408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialists, PLLC (NWMS)</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>January 11, 2023</last_update_submitted>
  <last_update_submitted_qc>January 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2023</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>
  <!-- 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/NCT04432454
org study id: SMX 20-001
nct id: NCT04432454
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, multicenter, single-arm safety study evaluating the safety and
      tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and
      postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer who have
      disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease
      and have an ESR1 mutation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit.
time frame: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months.
description: AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
measure: Progression free survival (PFS)
time frame: Up to 24 months
description: PFS is defined as the time from the date of entry into the study to the earliest date of first documented progression or death due to any cause.
measure: Clinical benefit rate (CBR)
time frame: 24 weeks or longer
measure: Objective response rate (ORR)
time frame: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months.
measure: Duration of response (DoR)
time frame: DoR will be assessed up to 24 months.
description: DoR is from the date of first documented response (CR or PR) to the date of first documented progression of disease or death due to any cause.
measure: Time to response
time frame: Time to response will be assessed up to 24 months.
description: From the date of entry into the study to the date of first documented response (CR or PR).
measure: Steady-state pharmacokinetics (PK) sampling for lasofoxifene and abemaciclib concentrations as well as abemaciclib's 3 major metabolites
time frame: Baseline and pre-dose at every visit starting at Visit 0 (Day 1) through Visit 4 (Week 8) and at the Final/ET visit if this occurred prior to Week 8
arm group label: Treatment
arm group type: Experimental
description: Women who have locally advanced or metastatic ER+/HER2- breast cancer and disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation
intervention type: Drug
intervention name: Lasofoxifene and abemaciclib (VERZENIO (R)).
description: Lasofoxifene 5 mg given once a day orally and abemaciclib 150 mg given twice a day orally.
arm group label: Treatment
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms