<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/NCT03004534</url>
  </required_header>
  <id_info>
    <org_study_id>TRIO030</org_study_id>
    <secondary_id>2016-004151-79</secondary_id>
    <secondary_id>HC6-24-c 201058</secondary_id>
    <nct_id>NCT03004534</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Changes in Human Breast Cancer Tissue Following Short-Term Use of Darolutamide</brief_title>
  <official_title>A Presurgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide (ODM-201)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Translational Research in Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Translational Research in Oncology</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of short-term treatment with darolutamide&#xD;
      on breast cancer cells (i.e., how the treatment may change the genes or proteins in breast&#xD;
      cancer cells) and to evaluate its safety and the way it is tolerated by subjects.&#xD;
&#xD;
      The intent is to study these changes in order to have a better understanding of the potential&#xD;
      use of darolutamide for women with EBC, know which patients are likely or unlikely to respond&#xD;
      to this treatment, and determine how darolutamide may be combined with other anti-cancer&#xD;
      drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This current study will enroll EBC subjects with differing breast cancer (BC) subtypes, with&#xD;
      the intent of characterizing the molecular alterations in BC tissue before and after&#xD;
      short-term exposure to the anti-androgen darolutamide. Studying the biological mechanisms in&#xD;
      which darolutamide targets the androgen receptor (AR) in BC will be crucial in understanding&#xD;
      its' potential role, as well as provide the foundation for further development of&#xD;
      darolutamide in this disease.&#xD;
&#xD;
      TRIO030 will evaluate the following objectives: Primary -To identify the molecular&#xD;
      alterations that occur in human BC tissue, following short-term exposure to darolutamide in&#xD;
      female subjects with EBC; Secondary - To evaluate the safety and tolerability of short-term&#xD;
      exposure to darolutamide in female subjects with EBC.&#xD;
&#xD;
      Design: This will be a multi-center, open-label, tissue-acquisition study involving up to 60&#xD;
      subjects from approximately 20 sites in North America and Europe, and will enroll EBC&#xD;
      subjects of differing subtypes (i.e., triple negative [TNBC], ER+/HER2-, and HER2+), with the&#xD;
      intent of characterizing the molecular alterations in BC tissue before and after short-term&#xD;
      exposure to the anti-androgen darolutamide.&#xD;
&#xD;
      Such information may suggest that darolutamide be combined with other modalities; for&#xD;
      example, if treatment with the drug is discovered to affect multiple signaling pathways.&#xD;
      Molecular profiling of tumor samples before and after darolutamide treatment may permit the&#xD;
      identification of patients likely or unlikely to respond to the agent based on the biological&#xD;
      and molecular characteristics of their tumors.&#xD;
&#xD;
      Duration: It is recommended that the surgery date is defined prior to starting protocol&#xD;
      treatment and then the start date of darolutamide (Day 1) will be derived as minus 14 to 21&#xD;
      days from the scheduled surgery date. Treatment will be taken until the day prior to surgery&#xD;
      or when the subject is ordered to stop all oral intake (i.e., &quot;nil per os&quot; (npo)), which ever&#xD;
      occurs first. If for some reason surgery takes place more than 21 days after treatment start,&#xD;
      it is acceptable that the subject receives darolutamide for more than 21 days and up to a&#xD;
      maximum of 35 days; subject should continue protocol treatment until the day prior to&#xD;
      surgery, or npo is ordered. In these cases it is strongly recommended to have surgery&#xD;
      performed as soon as possible after 21 days of treatment are completed.&#xD;
&#xD;
      After surgery, an End of Study (EoS) visit will occur 30 days (+/- 3 days) after the&#xD;
      subject's last intake of darolutamide. In case of ongoing protocol treatment-related AEs/SAEs&#xD;
      at the time of the EoS visit, monitoring of these events will continue as clinically&#xD;
      indicated until (a) the events have resolved or (b) the events have reached a status which,&#xD;
      in the Investigator's opinion, is unlikely to resolve due to the nature of the condition&#xD;
      and/or the subject's underlying disease.&#xD;
&#xD;
      Total Number of Sites: A total of 14 sites were opened worldwide, with 5 sites located within&#xD;
      the U.S, 6 in Canada, and 3 in Germany.&#xD;
&#xD;
      Sample Size/Patient Population: Up to 60 subjects will be enrolled in the study. To be able&#xD;
      to assess the molecular alterations after darolutamide, exposure in different BC subtypes,&#xD;
      subjects being either triple-negative, or ER+/HER2 negative, or HER2 positive, will be&#xD;
      enrolled in the study. Up to 20 subjects with each of these subtypes will be included (with&#xD;
      an acceptable minimum of 8 evaluable patients in each cohort).&#xD;
&#xD;
      Dosage Regimen: Darolutamide will be given at a dose of 600 mg (2 x 300 mg tablets) twice&#xD;
      daily (b.i.d) to a daily dose of 1200 mg.&#xD;
&#xD;
      The first day of darolutamide administration in the study is considered Day 1. The last&#xD;
      darolutamide intake will be on the day prior to breast cancer surgery, when the pre-surgery&#xD;
      visit should occur.&#xD;
&#xD;
      darolutamide should be taken approximately at the same time each day twice a day. It is&#xD;
      recommended that darolutamide be taken with food; recommendation is to take it with breakfast&#xD;
      and dinner each day.&#xD;
&#xD;
      Supportive measures and dose modifications: A subject who experiences a treatment-related&#xD;
      grade 3 or higher adverse event (AE) must be withdrawn from protocol treatment and should&#xD;
      proceed to surgery and undergo an EoS visit. In the case of a grade 1-2 treatment-related AE,&#xD;
      the Investigator should contact the Medical Monitor if a dose reduction or treatment hold is&#xD;
      required.&#xD;
&#xD;
      Washout pre-trial: Prior treatment of ovarian hormone replacement therapy should be stopped&#xD;
      at least 28 days prior to registration. Use of other investigational drugs should be stopped&#xD;
      within 28 days of enrollment. No major surgery within 28 days before enrollment (Major&#xD;
      surgery is defined as requiring a general anesthesia or respiratory assistance; involving&#xD;
      openings into the great cavities of the body, organs removed, or normal anatomy altered;&#xD;
      implying risks of severe hemorrhage; implying risk for life of the patient or severe&#xD;
      disability).&#xD;
&#xD;
      Concomitant Medication: Subjects will be instructed to consult with the Investigator before&#xD;
      taking any medications (including over-the-counter medications). Supportive medications may&#xD;
      be provided prophylactically or therapeutically per Investigator discretion.&#xD;
&#xD;
      Any concomitant treatment NOT listed below is considered permitted in the study and may be&#xD;
      prescribed as clinically appropriate during the study:&#xD;
&#xD;
        -  Investigational agents other than the protocol treatment.&#xD;
&#xD;
        -  Any additional standard or investigational anticancer agents, such as chemotherapy,&#xD;
           immunotherapy, targeted/biologic therapy, endocrine therapy, etc., even if utilized as&#xD;
           treatment of non-cancer indications. darolutamide must be permanently discontinued upon&#xD;
           initiation of a non-protocol standard or investigational antineoplastic therapy prior to&#xD;
           surgery.&#xD;
&#xD;
      Rescue Medication and Risk Management: No specific pre-medication is required. Based on the&#xD;
      current available data , there are no special warnings and precautions associated with the&#xD;
      use of darolutamide.&#xD;
&#xD;
      Premature Withdrawal / Discontinuation Criteria: The patient may withdraw from the study at&#xD;
      any time without prejudicing future medical treatment. In any case, the withdrawal should be&#xD;
      clearly documented in the subject's clinical records.&#xD;
&#xD;
      Should a patient decide to withdraw consent, all efforts will be made to complete and report&#xD;
      the observations as thoroughly as possible. A complete final evaluation at the time of the&#xD;
      patient's withdrawal should be made with an explanation of why the patient is withdrawing&#xD;
      from the study. After complete withdrawal of consent, no further study procedure is performed&#xD;
      and no further data will be collected.&#xD;
&#xD;
      Discontinuation: The Investigator will also discontinue protocol treatment if any of the&#xD;
      following conditions is met:&#xD;
&#xD;
        -  Intercurrent illness or a change in subject´s condition or unacceptable toxicity that&#xD;
           warrants protocol treatment discontinuation according to Investigator's judgment&#xD;
&#xD;
        -  Any event, condition, criterion which would warrant discontinuation of darolutamide&#xD;
           (i.e., severe toxicities), including grade ≥ 3 protocol-treatment related AE&#xD;
&#xD;
        -  Any event, condition, reason which would warrant darolutamide to be held for more than&#xD;
           the maximum acceptable delay of 7 consecutive days&#xD;
&#xD;
        -  Subject receives non-protocol anti-cancer therapy at any time during the protocol&#xD;
           treatment&#xD;
&#xD;
        -  Subject's decision to withdraw protocol treatment&#xD;
&#xD;
        -  Lost to follow up&#xD;
&#xD;
        -  Death&#xD;
&#xD;
        -  Pregnancy&#xD;
&#xD;
        -  Investigator's decision&#xD;
&#xD;
        -  Discontinuation of the study by the sponsor&#xD;
&#xD;
        -  Patient is enrolled but does not receive protocol treatment for any reason&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">March 13, 2019</completion_date>
  <primary_completion_date type="Actual">February 14, 2019</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>Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.</measure>
    <time_frame>1 year, 6 months</time_frame>
    <description>Androgen Receptor (AR) was assessed on the collected samples.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03</measure>
    <time_frame>1 year, 6 months</time_frame>
    <description>The assessment of safety will be performed for all subjects who have taken at least one tablet of darolutamide (defined as the &quot;safety population&quot;)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>Presurgical Molecular Assessment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>darolutamide</intervention_name>
    <description>Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
    <arm_group_label>Presurgical Molecular Assessment</arm_group_label>
    <other_name>BAY 1841788</other_name>
    <other_name>ODM-201</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and dated PICF obtained prior to initiation of any study-specific procedure and&#xD;
             treatment.&#xD;
&#xD;
          2. Female ≥ 18 years old.&#xD;
&#xD;
          3. Histologically proven invasive breast carcinoma (through either a core needle biopsy&#xD;
             or an incisional biopsy) for which surgery is indicated as the primary treatment&#xD;
             modality. Patients for which Neoadjuvant Systemic Therapy (NAST) is indicated are also&#xD;
             eligible provided they are willing to undergo a biopsy after completing treatment with&#xD;
             darolutamide and prior to NAST start.&#xD;
&#xD;
          4. Known ER, PgR and HER2 statuses.&#xD;
&#xD;
          5. Tumor must be confined to either the breast or to the breast and ipsilateral axilla&#xD;
             (Note: patinets with multifocal/multicentric tumors are eligible). Patient must have&#xD;
             (according to TNM 7th edition rules):&#xD;
&#xD;
               -  T1 with T ≥1.0cm, T2 or T3 by at least one radiographic or clinical measurement&#xD;
&#xD;
               -  Either clinically positive (N1 only) or clinically negative axillary nodes (N0)&#xD;
&#xD;
               -  M0&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.&#xD;
&#xD;
          7. Adequate organ function within 28 days prior to enrollment, as defined by the&#xD;
             following criteria:&#xD;
&#xD;
               -  Hematology: Hemoglobin ≥ 9.0 g/dl; ANC ≥ 1.5 × 109/L; Platelet count ≥ 100 ×&#xD;
                  109/L&#xD;
&#xD;
               -  Liver function: ALT and AST ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 × ULN (or ≤ 3&#xD;
                  times ULN for patients with documented Gilbert's syndrome or for whom indirect&#xD;
                  bilirubin concentrations suggest an extra-hepatic source of elevation)&#xD;
&#xD;
               -  Renal function: Creatinine ≤ 2.0 × ULN&#xD;
&#xD;
          8. No more than 42 days should elapse from the day study-specific tumor sample is taken&#xD;
             at initial diagnosis (or subsequent procedure) to the day of the first intake of&#xD;
             darolutamide.&#xD;
&#xD;
          9. Women of childbearing potential (WoCBP)* must agree to use acceptable non-hormonal&#xD;
             contraceptive methods of birth control from the day of the screening pregnancy test&#xD;
             and up to 3 months after the last intake of darolutamide.&#xD;
&#xD;
         10. For WoCBP* negative serum pregnancy test within 7 days of enrollment.&#xD;
&#xD;
         11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests, and biopsies as detailed in the protocol.&#xD;
&#xD;
               -  Note: WoCBP are any women between menarche and menopause who have not been&#xD;
                  permanently sterilized, capable of procreation. Permanent sterilization includes&#xD;
                  hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but&#xD;
                  excludes bilateral tubal ligation/occlusion. Postmenopause is defined as:&#xD;
                  Bilateral oophorectomy; Age ≥ 60; Age &lt; 60 and amenorrheic for ≥ 12 months in the&#xD;
                  absence of an alternative medical cause and FSH and estradiol in postmenopausal&#xD;
                  ranges.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any T0, Tis, T1 &lt; 1.0 cm, T4; or N2-3; or M1 BC.&#xD;
&#xD;
          2. Bilateral invasive BC.&#xD;
&#xD;
          3. Patient that underwent excisional biopsy of the primary tumor.&#xD;
&#xD;
          4. Medical indication or patient desire to undergo BC surgery or start NAST prior to&#xD;
             completing at least 14 days of treatment with darolutamide, and or refusal of patient&#xD;
             to undergo corresponding biopsy in case NAST is planned.&#xD;
&#xD;
          5. Prior or concurrent systemic anticancer therapy for BC treatment(immunotherapy,&#xD;
             hormonotherapy, biologic/targeted therapy, chemotherapy, investigational agents).&#xD;
&#xD;
          6. Prior or concurrent ipsilateral radiation therapy for invasive or noninvasive BC.&#xD;
&#xD;
          7. Prior or concurrent treatment or preventative use of any hormonal agent such as&#xD;
             aromatase inhibitors (AI), fulvestrant, raloxifene, tamoxifen or other SERM, or with&#xD;
             any other hormonal agent used for the treatment or prevention of BC or for any other&#xD;
             indication (e.g. osteoporosis).&#xD;
&#xD;
          8. Concurrent use of ovarian hormone replacement therapy. Prior treatment should be&#xD;
             stopped at least 28 days prior to registration.&#xD;
&#xD;
          9. Prior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.&#xD;
&#xD;
         10. Use of other investigational drug within 28 days of enrollment.&#xD;
&#xD;
         11. Major surgery* within 28 days before enrollment.&#xD;
&#xD;
         12. Any concurrent or previous malignancy within 5 years prior to enrollment except for&#xD;
             basal or squamous skin cancer, or carcinoma in situ of the cervix, or other&#xD;
             non-invasive/in-situ neoplasm, all of which must have been adequately and radically&#xD;
             treated. A patient with previous history of invasive malignancy (other than adequately&#xD;
             and radically treated basal or squamous skin cancer) is eligible provided that she has&#xD;
             been disease free for more than 5 years.&#xD;
&#xD;
         13. Severe or uncontrolled concurrent disease, infection or comorbidity.&#xD;
&#xD;
         14. Known active viral hepatitis, HIV or chronic liver disease.&#xD;
&#xD;
         15. Other serious illness or medical condition within 6 months before enrollment,&#xD;
             including any of the following: Concurrent congestive heart failure NYHA Class III or&#xD;
             IV, severe/unstable angina pectoris, myocardial infarction, uncontrolled hypertension,&#xD;
             coronary/peripheral artery bypass graft, high-risk uncontrolled arrhythmias, stroke.&#xD;
&#xD;
         16. Any contraindication to oral agents or gastrointestinal disorder or procedure which&#xD;
             expects to interfere significantly with absorption of protocol treatment.&#xD;
&#xD;
         17. History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
             might confound the results of the trial, interfere with the patient's participation&#xD;
             for the full duration of the trial, or is not in the best interest of the patient to&#xD;
             participate, in the opinion of the treating investigator.&#xD;
&#xD;
         18. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the trial.&#xD;
&#xD;
         19. Known allergy to darolutamide or any of the excipients.&#xD;
&#xD;
         20. Pregnant or lactating darolutamide. * Note: Major surgery defined as requiring a&#xD;
             general anesthesia or respiratory assistance; involving openings into the great&#xD;
             cavities of the body, organs removed, or normal anatomy altered; implying risks of&#xD;
             severe hemorrhage; implying risk for life of the patient or severe disability.&#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>Rodrigo Fresco, MD</last_name>
    <role>Study Director</role>
    <affiliation>Translational Research in Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095-1678</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Breast Care and Women's Health Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>91405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Physician Network, Cancer Care Associates</name>
      <address>
        <city>Redondo Beach</city>
        <state>California</state>
        <zip>90277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Medical Oncology</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <zip>93454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Cancer Center - Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>(CIUSSS) de l'Est-de-l'Île-de-Montréal - l'Hôpital Maisonneuve-Rosemont</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1T 2M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Affilie Universitaire De Quebec - Hospital Du Saint-Sacrement</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Erlangen</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interdisziplinares Onkologisches Zentrum</name>
      <address>
        <city>Muenchen</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Women's Health</name>
      <address>
        <city>Tubingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <results_first_submitted>March 4, 2020</results_first_submitted>
  <results_first_submitted_qc>March 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 3, 2020</results_first_posted>
  <last_update_submitted>March 19, 2020</last_update_submitted>
  <last_update_submitted_qc>March 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>Breast Carcinoma</keyword>
  <keyword>Breast Tumours</keyword>
  <keyword>Early Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03004534/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03004534/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The screening period starts with registration (which is informed consent signature) and ends when the patient is enrolled (following eligibility central review confirmation by TRIO) or screen failed.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Presurgical Molecular Assessment</title>
          <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.&#xD;
darolutamide: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>36 patients were enrolled in total. The evaluable population was used for the performance of molecular assays - 35 patients were evaluable based on the clinical criteria (of these 34 were evaluable for molecular analysis based on the adequacy of the tumor tissue collected).</population>
      <group_list>
        <group group_id="B1">
          <title>Presurgical Molecular Assessment</title>
          <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.&#xD;
darolutamide: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.5" lower_limit="32.0" upper_limit="82.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Adults (18-64 years)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adults (65-84 years)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </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="36"/>
                  </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>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Menopausal Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Postmenopausal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Premenopausal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Breast Cancer Sub-Type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Triple-negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HR+/HER2 negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HER2 positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>The ECOG Scale of Performance Status is a measurement used to describe a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.).&#xD;
Patients with ECOG 0 are in better general condition than patients with ECOG 1:&#xD;
0 = Fully active, able to carry on all pre-disease performance without restriction.&#xD;
1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>ECOG 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.</title>
        <description>Androgen Receptor (AR) was assessed on the collected samples.</description>
        <time_frame>1 year, 6 months</time_frame>
        <population>36 patients were enrolled, however 34 patients were evaluable based on the molecular criteria: Adequacy (evaluated by the central laboratory) for molecular assessment of the tumor tissue collected before and after the protocol treatment initiation. Expression levels were evaluated by microarray using the patient's RNA.</population>
        <group_list>
          <group group_id="O1">
            <title>Presurgical Molecular Assessment</title>
            <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.&#xD;
darolutamide: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.</title>
          <description>Androgen Receptor (AR) was assessed on the collected samples.</description>
          <population>36 patients were enrolled, however 34 patients were evaluable based on the molecular criteria: Adequacy (evaluated by the central laboratory) for molecular assessment of the tumor tissue collected before and after the protocol treatment initiation. Expression levels were evaluated by microarray using the patient's RNA.</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="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Androgen Receptor - Up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Androgen Receptor - Unchanged</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Androgen Receptor - Down</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03</title>
        <description>The assessment of safety will be performed for all subjects who have taken at least one tablet of darolutamide (defined as the &quot;safety population&quot;)</description>
        <time_frame>1 year, 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Presurgical Molecular Assessment</title>
            <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.&#xD;
darolutamide: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03</title>
          <description>The assessment of safety will be performed for all subjects who have taken at least one tablet of darolutamide (defined as the &quot;safety population&quot;)</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="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No. of Patients with a TEAE</title>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No. of Patients without a TEAE</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year, 6 months.</time_frame>
      <desc>The Safety population includes all patients who have taken at least one tablet of darolutamide. The following information was collected: description of event, start/stop dates, worst grade experienced (severity/intensity), seriousness, action taken on protocol treatment, and relationship to protocol treatment. The intensity of AEs were classified and recorded according to NCI CTCAE version 4.03. All adverse experiences observed by the Investigator or reported by the patient were collected.</desc>
      <group_list>
        <group group_id="E1">
          <title>Presurgical Molecular Assessment</title>
          <description>Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.&#xD;
darolutamide: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="26" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nasea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALAT Increase</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>ASAT Increase</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </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>No publication, abstract or presentation of the study will be made without the approval of the Study Steering Committee (SSC).</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Project Management</name_or_title>
      <organization>Translational Research In Oncology (TRIO)</organization>
      <phone>33 158 10 09 09</phone>
      <email>030@trioncology.org</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/NCT03004534
org study id: TRIO030
secondary id: 2016-004151-79
secondary id: HC6-24-c 201058
nct id: NCT03004534
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the effect of short-term treatment with darolutamide
      on breast cancer cells (i.e., how the treatment may change the genes or proteins in breast
      cancer cells) and to evaluate its safety and the way it is tolerated by subjects.

      The intent is to study these changes in order to have a better understanding of the potential
      use of darolutamide for women with EBC, know which patients are likely or unlikely to respond
      to this treatment, and determine how darolutamide may be combined with other anti-cancer
      drugs.
This current study will enroll EBC subjects with differing breast cancer (BC) subtypes, with
      the intent of characterizing the molecular alterations in BC tissue before and after
      short-term exposure to the anti-androgen darolutamide. Studying the biological mechanisms in
      which darolutamide targets the androgen receptor (AR) in BC will be crucial in understanding
      its' potential role, as well as provide the foundation for further development of
      darolutamide in this disease.

      TRIO030 will evaluate the following objectives: Primary -To identify the molecular
      alterations that occur in human BC tissue, following short-term exposure to darolutamide in
      female subjects with EBC; Secondary - To evaluate the safety and tolerability of short-term
      exposure to darolutamide in female subjects with EBC.

      Design: This will be a multi-center, open-label, tissue-acquisition study involving up to 60
      subjects from approximately 20 sites in North America and Europe, and will enroll EBC
      subjects of differing subtypes (i.e., triple negative [TNBC], ER+/HER2-, and HER2+), with the
      intent of characterizing the molecular alterations in BC tissue before and after short-term
      exposure to the anti-androgen darolutamide.

      Such information may suggest that darolutamide be combined with other modalities; for
      example, if treatment with the drug is discovered to affect multiple signaling pathways.
      Molecular profiling of tumor samples before and after darolutamide treatment may permit the
      identification of patients likely or unlikely to respond to the agent based on the biological
      and molecular characteristics of their tumors.

      Duration: It is recommended that the surgery date is defined prior to starting protocol
      treatment and then the start date of darolutamide (Day 1) will be derived as minus 14 to 21
      days from the scheduled surgery date. Treatment will be taken until the day prior to surgery
      or when the subject is ordered to stop all oral intake (i.e., "nil per os" (npo)), which ever
      occurs first. If for some reason surgery takes place more than 21 days after treatment start,
      it is acceptable that the subject receives darolutamide for more than 21 days and up to a
      maximum of 35 days; subject should continue protocol treatment until the day prior to
      surgery, or npo is ordered. In these cases it is strongly recommended to have surgery
      performed as soon as possible after 21 days of treatment are completed.

      After surgery, an End of Study (EoS) visit will occur 30 days (+/- 3 days) after the
      subject's last intake of darolutamide. In case of ongoing protocol treatment-related AEs/SAEs
      at the time of the EoS visit, monitoring of these events will continue as clinically
      indicated until (a) the events have resolved or (b) the events have reached a status which,
      in the Investigator's opinion, is unlikely to resolve due to the nature of the condition
      and/or the subject's underlying disease.

      Total Number of Sites: A total of 14 sites were opened worldwide, with 5 sites located within
      the U.S, 6 in Canada, and 3 in Germany.

      Sample Size/Patient Population: Up to 60 subjects will be enrolled in the study. To be able
      to assess the molecular alterations after darolutamide, exposure in different BC subtypes,
      subjects being either triple-negative, or ER+/HER2 negative, or HER2 positive, will be
      enrolled in the study. Up to 20 subjects with each of these subtypes will be included (with
      an acceptable minimum of 8 evaluable patients in each cohort).

      Dosage Regimen: Darolutamide will be given at a dose of 600 mg (2 x 300 mg tablets) twice
      daily (b.i.d) to a daily dose of 1200 mg.

      The first day of darolutamide administration in the study is considered Day 1. The last
      darolutamide intake will be on the day prior to breast cancer surgery, when the pre-surgery
      visit should occur.

      darolutamide should be taken approximately at the same time each day twice a day. It is
      recommended that darolutamide be taken with food; recommendation is to take it with breakfast
      and dinner each day.

      Supportive measures and dose modifications: A subject who experiences a treatment-related
      grade 3 or higher adverse event (AE) must be withdrawn from protocol treatment and should
      proceed to surgery and undergo an EoS visit. In the case of a grade 1-2 treatment-related AE,
      the Investigator should contact the Medical Monitor if a dose reduction or treatment hold is
      required.

      Washout pre-trial: Prior treatment of ovarian hormone replacement therapy should be stopped
      at least 28 days prior to registration. Use of other investigational drugs should be stopped
      within 28 days of enrollment. No major surgery within 28 days before enrollment (Major
      surgery is defined as requiring a general anesthesia or respiratory assistance; involving
      openings into the great cavities of the body, organs removed, or normal anatomy altered;
      implying risks of severe hemorrhage; implying risk for life of the patient or severe
      disability).

      Concomitant Medication: Subjects will be instructed to consult with the Investigator before
      taking any medications (including over-the-counter medications). Supportive medications may
      be provided prophylactically or therapeutically per Investigator discretion.

      Any concomitant treatment NOT listed below is considered permitted in the study and may be
      prescribed as clinically appropriate during the study:

        -  Investigational agents other than the protocol treatment.

        -  Any additional standard or investigational anticancer agents, such as chemotherapy,
           immunotherapy, targeted/biologic therapy, endocrine therapy, etc., even if utilized as
           treatment of non-cancer indications. darolutamide must be permanently discontinued upon
           initiation of a non-protocol standard or investigational antineoplastic therapy prior to
           surgery.

      Rescue Medication and Risk Management: No specific pre-medication is required. Based on the
      current available data , there are no special warnings and precautions associated with the
      use of darolutamide.

      Premature Withdrawal / Discontinuation Criteria: The patient may withdraw from the study at
      any time without prejudicing future medical treatment. In any case, the withdrawal should be
      clearly documented in the subject's clinical records.

      Should a patient decide to withdraw consent, all efforts will be made to complete and report
      the observations as thoroughly as possible. A complete final evaluation at the time of the
      patient's withdrawal should be made with an explanation of why the patient is withdrawing
      from the study. After complete withdrawal of consent, no further study procedure is performed
      and no further data will be collected.

      Discontinuation: The Investigator will also discontinue protocol treatment if any of the
      following conditions is met:

        -  Intercurrent illness or a change in subject´s condition or unacceptable toxicity that
           warrants protocol treatment discontinuation according to Investigator's judgment

        -  Any event, condition, criterion which would warrant discontinuation of darolutamide
           (i.e., severe toxicities), including grade ≥ 3 protocol-treatment related AE

        -  Any event, condition, reason which would warrant darolutamide to be held for more than
           the maximum acceptable delay of 7 consecutive days

        -  Subject receives non-protocol anti-cancer therapy at any time during the protocol
           treatment

        -  Subject's decision to withdraw protocol treatment

        -  Lost to follow up

        -  Death

        -  Pregnancy

        -  Investigator's decision

        -  Discontinuation of the study by the sponsor

        -  Patient is enrolled but does not receive protocol treatment for any reason
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.
time frame: 1 year, 6 months
description: Androgen Receptor (AR) was assessed on the collected samples.
measure: Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03
time frame: 1 year, 6 months
description: The assessment of safety will be performed for all subjects who have taken at least one tablet of darolutamide (defined as the "safety population")
arm group label: Presurgical Molecular Assessment
arm group type: Experimental
description: Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.
intervention type: Drug
intervention name: darolutamide
description: Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.
arm group label: Presurgical Molecular Assessment
other name: BAY 1841788
other name: ODM-201
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rodrigo Fresco, MD
role: Study Director
affiliation: Translational Research in Oncology
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country: Canada
country: Germany
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: Undecided
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