xml: <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/NCT06001762</url>
    </required_header>
    <id_info>
      <org_study_id>23-355</org_study_id>
      <nct_id>NCT06001762</nct_id>
    </id_info>
    <brief_title>TRADE: Dose Escalation Tolerability of Abemaciclib in HR+ HER2- Early Stage Breast Cancer</brief_title>
    <official_title>The TRADE Study: A Phase 2 Trial to Assess the ToleRability of Abemaciclib Dose Escalation in Patients With Early-Stage HR-positive and HER2-negative Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Dana-Farber Cancer Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Eli Lilly and Company</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Dana-Farber Cancer Institute</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        In this research study, investigators are testing if a dose-increasing strategy for&#xD;
        abemaciclib will have less side effects and be better tolerated than the standard dosage of&#xD;
        abemaciclib for participants with early-stage high-risk hormone receptor positive breast&#xD;
        cancer.&#xD;
  &#xD;
        The names of the study drugs involved in this study are:&#xD;
  &#xD;
          -  Abemaciclib (CDK4 and CDK6 inhibitor)&#xD;
  &#xD;
          -  Tamoxifen (Selective estrogen receptor modulator)&#xD;
  &#xD;
          -  Anastrozole/Letrozole (Non-steroidal aromatase inhibitors)&#xD;
  &#xD;
          -  Exemestane (steroidal aromatase inhibitor)&#xD;
  &#xD;
          -  LHRH (Gonadotropin-releasing hormone agonist, or Luteinizing hormone-releasing hormone&#xD;
             agonist)&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This research study is a prospective, single-arm, open label, phase 2 study designed to&#xD;
        evaluate if a dose-increasing strategy for abemaciclib will have less side effects and be&#xD;
        better tolerated than the standard dosage of abemaciclib for participants with early-stage&#xD;
        high-risk hormone receptor positive breast cancer.&#xD;
  &#xD;
        This research study involves adjuvant abemaciclib plus endocrine (anti-hormone) therapy that&#xD;
        works to target breast cancer. Adjuvant therapy is treatment given after surgery,&#xD;
        chemotherapy, and/or radiation therapy.&#xD;
  &#xD;
        The U.S. Food and Drug Administration (FDA) has approved abemaciclib as a treatment option&#xD;
        for early-stage high-risk hormone receptor breast cancer. The FDA has also approved hormonal&#xD;
        therapies as treatment for hormone receptor positive breast cancer.&#xD;
  &#xD;
        The research study procedures include screening for eligibility, study treatment including&#xD;
        laboratory evaluations and questionnaires, blood tests, tumor biopsies, and stool&#xD;
        collections.&#xD;
  &#xD;
        Participation in this research study is expected to last for at least 2 years and up to 5&#xD;
        years.&#xD;
  &#xD;
        It is expected that about 90 people will take part in this research study.&#xD;
  &#xD;
        Eli Lilly and Company is supporting this study by providing funding for the study and&#xD;
        supplying the study drug, abemaciclib.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">February 2024</start_date>
    <completion_date type="Anticipated">January 1, 2027</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2026</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>Composite Adverse Rate at 3 months</measure>
      <time_frame>3 months</time_frame>
      <description>The rate of the composite endpoint will be reported, including disaggregated and combined rates of treatment discontinuations and/or dose reductions at 3 months.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of Grade 2-4 Diarrhea</measure>
      <time_frame>Up to 26 weeks</time_frame>
      <description>Incidence of grade 2-4 diarrhea will be reported as frequencies and absolute numbers based on CTCAE5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite Rate of Abemaciclib</measure>
      <time_frame>Up to 25 weeks</time_frame>
      <description>The composite rate will be reported, including disaggregated and combined rates of treatment discontinuations, dose reductions, dose holds, and inability to reach or maintain the target dose.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Treatment-Related Adverse Events</measure>
      <time_frame>Up to 25 weeks</time_frame>
      <description>The incidence of treatment-related adverse events will be reported as frequencies and absolute numbers based on CTCAT5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of Inability to Reach the Full Dose</measure>
      <time_frame>Up to 25 weeks</time_frame>
      <description>Rate of inability to reach the full dose will be reported as the rate of participants who have never reached the full dose at 150mg BID.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Therapeutic Adherence to Oral Adjuvant Therapy</measure>
      <time_frame>Up to 25 weeks</time_frame>
      <description>Ratio of the self-reported number of pills taken and number of pills prescribed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Intensity of Abemaciclib</measure>
      <time_frame>12 weeks</time_frame>
      <description>Rate of patients at full dose (150mg BID) at 12 w versus those unable to reach full dose</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Early-stage Breast Cancer</condition>
    <condition>High Risk Breast Carcinoma</condition>
    <arm_group>
      <arm_group_label>Abemaciclib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Study procedures will be conducted as follows:&#xD;
  Cycles 1 - 24&#xD;
  Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day.&#xD;
  Endocrine therapy 1 x per day.&#xD;
  In clinic visits with blood tests, questionnaires, and assessments:&#xD;
  Day 1 of Cycles 1, 2, and 3&#xD;
  Day 15 of Cycles 1 and 2&#xD;
  Every three cycles after Cycle 3 Day 1.&#xD;
  End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Abemaciclib</intervention_name>
      <description>CDK4 and CDK6 inhibitor, tablet taken orally</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tamoxifen</intervention_name>
      <description>Selective estrogen receptor modulator, taken orally per institutional standard of care</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Anastrozole</intervention_name>
      <description>Non-steroidal aromatase inhibitor, taken orally per institutional standard of care</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Letrozole</intervention_name>
      <description>Non-steroidal aromatase inhibitor, taken orally per institutional standard of care</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Exemestane</intervention_name>
      <description>Steroidal aromatase inhibitor, taken orally per institutional standard of care</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>LHRH Agonist</intervention_name>
      <description>Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care</description>
      <arm_group_label>Abemaciclib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Stage II or III node-positive HR+/HER2- breast cancer per local laboratory assessment.&#xD;
  &#xD;
            -  Eligible participants must be appropriate candidates for adjuvant abemaciclib, per&#xD;
               assessment of their treating physician.&#xD;
  &#xD;
            -  Participants must be candidates for adjuvant endocrine therapy, which may have started&#xD;
               before or at time of entry onto the trial. Patient may be receiving adjuvant aromatase&#xD;
               inhibitor or tamoxifen, +/- ovarian suppression.&#xD;
  &#xD;
            -  Participants must have undergone definitive surgery of the primary breast tumor(s)&#xD;
               within 16 months of study entry.&#xD;
  &#xD;
            -  At least 21 days must have elapsed between last dose of chemotherapy and registration.&#xD;
               Participants who previously received chemotherapy must have recovered (Common&#xD;
               Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of&#xD;
               chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to&#xD;
               randomization.&#xD;
  &#xD;
            -  At least 14 days must have elapsed between end of radiotherapy and day 1 of treatment&#xD;
               with abemaciclib. Participants who received prior radiotherapy must have completed and&#xD;
               fully recovered from the acute effects of radiotherapy. No radiotherapy should be&#xD;
               planned to occur during study therapy.&#xD;
  &#xD;
            -  At least 14 days must have elapsed since most recent breast surgery prior to&#xD;
               registration and patient has recovered from side effects of prior surgery.&#xD;
  &#xD;
            -  Bilateral or multifocal/multicentric breast cancers that meet eligibility criteria are&#xD;
               allowed.&#xD;
  &#xD;
            -  ECOG performance status 0-1&#xD;
  &#xD;
            -  Men and women with any menopausal status ≥18 years of age&#xD;
  &#xD;
            -  Adequate organ function as defined below:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥ 1500 x 10^9/L&#xD;
  &#xD;
                 -  Platelets ≥ 100 x 10^9/L&#xD;
  &#xD;
                 -  Hemoglobin ≥ 8g/dL; patients may receive erythrocyte transfusions to achieve this&#xD;
                    hemoglobin level at the discretion of the investigator. Initial treatment must&#xD;
                    not begin earlier than the day after the erythrocyte transfusion.&#xD;
  &#xD;
                 -  Bilirubin ≤ 1.5 x ULN. For patients with Gilbert syndrome, the limit is ≤ 2 x&#xD;
                    institutional ULN AND direct bilirubin within the normal range of normality.&#xD;
  &#xD;
                 -  AST/ALT ≤ 3 x institutional ULN&#xD;
  &#xD;
            -  Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy&#xD;
               testing does not need to be pursued in female patients who are:&#xD;
  &#xD;
                 -  Age &gt; 60 years; or&#xD;
  &#xD;
                 -  Age &lt; 60 with intact uterus and amenorrhea for 12 consecutive months or more AND&#xD;
                    FSH/estradiol levels within postmenopausal range; or&#xD;
  &#xD;
                 -  Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal&#xD;
                    ligation.&#xD;
  &#xD;
            -  Women of child-bearing potential and men with partners of childbearing potential must&#xD;
               be willing to employ one highly effective form of nonhormonal contraception (with the&#xD;
               exception of hormonal IUDs) or two effective forms of nonhormonal contraception by the&#xD;
               patient and/or partner and continue its use for the duration of the study treatment&#xD;
               and for 3 months after the last dose of abemaciclib.&#xD;
  &#xD;
            -  Subject must be able to swallow and retain oral medication.&#xD;
  &#xD;
            -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
  &#xD;
            -  Non-English-speaking patients are eligible but will be exempt from patient-completed&#xD;
               questionnaires.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior treatment with any CDK4/6 inhibitor.&#xD;
  &#xD;
            -  Patients with node-negative breast cancer are not eligible for the trial.&#xD;
  &#xD;
            -  Concurrent therapy with other investigational agents.&#xD;
  &#xD;
            -  Diagnosis of inflammatory breast cancer (T4d).&#xD;
  &#xD;
            -  History of allergic reactions attributed to abemaciclib or similar chemical or&#xD;
               biologic composition or excipients.&#xD;
  &#xD;
            -  Participants with a history of malignancy are ineligible except in the following&#xD;
               circumstances:&#xD;
  &#xD;
               --Individuals with a history of invasive breast cancer are not eligible unless they&#xD;
               have been disease-free for a minimum of five years.&#xD;
  &#xD;
            -  Individuals with a malignancy history other than invasive breast cancer are eligible&#xD;
               if they have no active malignancy and are deemed by the investigator to be at low risk&#xD;
               for recurrence of that malignancy.&#xD;
  &#xD;
            -  Individuals with the following cancer history are eligible: adequately treated non-&#xD;
               melanoma skin cancers, curatively treated in situ cancer of the cervix, ductal&#xD;
               carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma. Other&#xD;
               exceptions may exist following review with the sponsor-investigator&#xD;
  &#xD;
            -  Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of&#xD;
               the investigator, would preclude participation in this study (for example,&#xD;
               interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe&#xD;
               renal impairment [e.g. estimated creatinine clearance &lt;30ml/min], history of major&#xD;
               surgical resection involving the stomach or small bowel, or preexisting uncontrolled&#xD;
               Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in&#xD;
               baseline Grade 2 or higher diarrhea) or other conditions that in the opinion of the&#xD;
               investigator limit compliance with study requirements.&#xD;
  &#xD;
            -  History of any of the following conditions: syncope of cardiovascular etiology,&#xD;
               ventricular arrhythmia of pathological origin (including, but not limited to,&#xD;
               ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.&#xD;
  &#xD;
            -  Any of the following due to teratogenic potential of the study drugs:&#xD;
  &#xD;
                 -  Pregnant women&#xD;
  &#xD;
                 -  Nursing women&#xD;
  &#xD;
                 -  Women of childbearing potential who are unwilling to employ adequate&#xD;
                    contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence,&#xD;
                    etc). Hormonal birth control methods are not permitted.&#xD;
  &#xD;
                 -  Men who are unwilling to employ adequate contraception (condoms, surgical&#xD;
                    sterilization, abstinence, etc).&#xD;
  &#xD;
            -  Receipt of an experimental treatment in a clinical trial within the last 30 days or 5&#xD;
               half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any&#xD;
               other type of medical research (for example: medical device) judged by the&#xD;
               sponsor-investigator not to be scientifically or medically compatible with this study.&#xD;
  &#xD;
            -  Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of&#xD;
               initiating study treatment) or invasive/ systemic fungal infection\&#xD;
  &#xD;
            -  For patients with known HIV infection, CD4 baseline count should be evaluated:&#xD;
               patients with a CDK count ≥ 350 cells/uL can be enrolled. Participants should be on&#xD;
               established anti-retroviral therapy (ART) for at least four weeks and have an HIV&#xD;
               viral load less than 400 copies/mL prior to enrollment. Potential pharmacological&#xD;
               interactions of the ART with abemaciclib and endocrine therapy must be reviewed,&#xD;
               particularly for the effects on CYP3A4.&#xD;
  &#xD;
            -  Patients with active or chronic Hepatitis B or C are eligible provided they meet liver&#xD;
               function laboratory criteria and cannot be on any medication with a known interaction&#xD;
               with the study agents.&#xD;
  &#xD;
            -  Participants receiving any medications or substances that are strong inhibitors or&#xD;
               inducers of CYP3A4, including selected herbals (e.g., hypericum) and food (e.g.,&#xD;
               grapefruit) known for pharmacological interactions, cannot be enrolled, due to&#xD;
               interference with the dose-escalation, unless the food or supplement has been&#xD;
               discontinued at least after an interval equivalent to 3-5 half-lives of the inhibitor.&#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>
    <overall_official>
      <last_name>Erica Mayer, MD, MPH</last_name>
      <role>Principal Investigator</role>
      <affiliation>Dana-Farber Cancer Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Erica Mayer, MD, MPH</last_name>
      <phone>(617) 632-3800</phone>
      <email>EMAYER@PARTNERS.ORG</email>
    </overall_contact>
    <location>
      <facility>
        <name>Beth Israel Deaconess Medical Center</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02215</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Shana Berwick, MD</last_name>
        <phone>617-667-2100</phone>
        <email>sberwick@bidmc.harvard.edu</email>
      </contact>
      <investigator>
        <last_name>Shana Berwick, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02215</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Erica Mayer, MD, MPH</last_name>
        <phone>617-632-3800</phone>
        <email>emayer@partners.org</email>
      </contact>
      <investigator>
        <last_name>Erica Mayer, MD, MPH</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute at Steward St. Elizabeth's</name>
        <address>
          <city>Brighton</city>
          <state>Massachusetts</state>
          <zip>02135</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Alys Malcolm, MD</last_name>
        <phone>617-632-4595</phone>
        <email>alys_malcolm@dfci.harvard.edu</email>
      </contact>
      <investigator>
        <last_name>Alys Malcolm, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute at Foxborough</name>
        <address>
          <city>Foxboro</city>
          <state>Massachusetts</state>
          <zip>02035</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Natalie Sinclair, MD</last_name>
        <phone>508-543-1700</phone>
        <email>natalie_sinclair@dfci.harvard.edu</email>
      </contact>
      <investigator>
        <last_name>Natalie Sinclair, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute at Merrimack Valley</name>
        <address>
          <city>Methuen</city>
          <state>Massachusetts</state>
          <zip>01844</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute at Milford</name>
        <address>
          <city>Milford</city>
          <state>Massachusetts</state>
          <zip>01757</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Natalie Sinclair, MD</last_name>
        <phone>508-543-1700</phone>
        <email>natalie_sinclair@dfci.harvard.edu</email>
      </contact>
      <investigator>
        <last_name>Natalie Sinclaire, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Institute at South Shore</name>
        <address>
          <city>South Weymouth</city>
          <state>Massachusetts</state>
          <zip>02190</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Meredith Faggen, MD</last_name>
        <phone>781-624-4800</phone>
        <email>Meredith_Faggen@dfci.harvard.edu</email>
      </contact>
      <investigator>
        <last_name>Meredith Faggeen, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Dana-Farber Cancer Insitute at Londonderry Hospital</name>
        <address>
          <city>Londonderry</city>
          <state>New Hampshire</state>
          <zip>03053</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
      <investigator_full_name>Erica Mayer, MD, MPH</investigator_full_name>
      <investigator_title>Principle Investigator</investigator_title>
    </responsible_party>
    <keyword>Breast Cancer</keyword>
    <keyword>Early-stage high-risk breast cancer</keyword>
    <keyword>Early-stage breast cancer</keyword>
    <keyword>High risk breast carcinoma</keyword>
    <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>Letrozole</mesh_term>
      <mesh_term>Anastrozole</mesh_term>
      <mesh_term>Exemestane</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
      <ipd_access_criteria>Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001762
  org study id: 23-355
  nct id: NCT06001762
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  In this research study, investigators are testing if a dose-increasing strategy for
        abemaciclib will have less side effects and be better tolerated than the standard dosage of
        abemaciclib for participants with early-stage high-risk hormone receptor positive breast
        cancer.
  
        The names of the study drugs involved in this study are:
  
          -  Abemaciclib (CDK4 and CDK6 inhibitor)
  
          -  Tamoxifen (Selective estrogen receptor modulator)
  
          -  Anastrozole/Letrozole (Non-steroidal aromatase inhibitors)
  
          -  Exemestane (steroidal aromatase inhibitor)
  
          -  LHRH (Gonadotropin-releasing hormone agonist, or Luteinizing hormone-releasing hormone
             agonist)
  This research study is a prospective, single-arm, open label, phase 2 study designed to
        evaluate if a dose-increasing strategy for abemaciclib will have less side effects and be
        better tolerated than the standard dosage of abemaciclib for participants with early-stage
        high-risk hormone receptor positive breast cancer.
  
        This research study involves adjuvant abemaciclib plus endocrine (anti-hormone) therapy that
        works to target breast cancer. Adjuvant therapy is treatment given after surgery,
        chemotherapy, and/or radiation therapy.
  
        The U.S. Food and Drug Administration (FDA) has approved abemaciclib as a treatment option
        for early-stage high-risk hormone receptor breast cancer. The FDA has also approved hormonal
        therapies as treatment for hormone receptor positive breast cancer.
  
        The research study procedures include screening for eligibility, study treatment including
        laboratory evaluations and questionnaires, blood tests, tumor biopsies, and stool
        collections.
  
        Participation in this research study is expected to last for at least 2 years and up to 5
        years.
  
        It is expected that about 90 people will take part in this research study.
  
        Eli Lilly and Company is supporting this study by providing funding for the study and
        supplying the study drug, abemaciclib.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Composite Adverse Rate at 3 months
  time frame: 3 months
  description: The rate of the composite endpoint will be reported, including disaggregated and combined rates of treatment discontinuations and/or dose reductions at 3 months.
  measure: Incidence of Grade 2-4 Diarrhea
  time frame: Up to 26 weeks
  description: Incidence of grade 2-4 diarrhea will be reported as frequencies and absolute numbers based on CTCAE5.0.
  measure: Composite Rate of Abemaciclib
  time frame: Up to 25 weeks
  description: The composite rate will be reported, including disaggregated and combined rates of treatment discontinuations, dose reductions, dose holds, and inability to reach or maintain the target dose.
  measure: Incidence of Treatment-Related Adverse Events
  time frame: Up to 25 weeks
  description: The incidence of treatment-related adverse events will be reported as frequencies and absolute numbers based on CTCAT5.0.
  measure: Rate of Inability to Reach the Full Dose
  time frame: Up to 25 weeks
  description: Rate of inability to reach the full dose will be reported as the rate of participants who have never reached the full dose at 150mg BID.
  measure: Therapeutic Adherence to Oral Adjuvant Therapy
  time frame: Up to 25 weeks
  description: Ratio of the self-reported number of pills taken and number of pills prescribed
  measure: Dose Intensity of Abemaciclib
  time frame: 12 weeks
  description: Rate of patients at full dose (150mg BID) at 12 w versus those unable to reach full dose
  arm group label: Abemaciclib
  arm group type: Experimental
  description: Study procedures will be conducted as follows:
  Cycles 1 - 24
  Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day.
  Endocrine therapy 1 x per day.
  In clinic visits with blood tests, questionnaires, and assessments:
  Day 1 of Cycles 1, 2, and 3
  Day 15 of Cycles 1 and 2
  Every three cycles after Cycle 3 Day 1.
  End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection.
  intervention type: Drug
  intervention name: Abemaciclib
  description: CDK4 and CDK6 inhibitor, tablet taken orally
  arm group label: Abemaciclib
  intervention type: Drug
  intervention name: Tamoxifen
  description: Selective estrogen receptor modulator, taken orally per institutional standard of care
  arm group label: Abemaciclib
  intervention type: Drug
  intervention name: Anastrozole
  description: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care
  arm group label: Abemaciclib
  intervention type: Drug
  intervention name: Letrozole
  description: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care
  arm group label: Abemaciclib
  intervention type: Drug
  intervention name: Exemestane
  description: Steroidal aromatase inhibitor, taken orally per institutional standard of care
  arm group label: Abemaciclib
  intervention type: Drug
  intervention name: LHRH Agonist
  description: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care
  arm group label: Abemaciclib
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Erica Mayer, MD, MPH
  role: Principal Investigator
  affiliation: Dana-Farber Cancer Institute
  last name: Erica Mayer, MD, MPH
  phone: (617) 632-3800
  email: EMAYER@PARTNERS.ORG
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  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Dana-Farber Cancer Institute
  investigator full name: Erica Mayer, MD, MPH
  investigator title: Principle Investigator
  mesh term: Breast Neoplasms
  mesh term: Tamoxifen
  mesh term: Letrozole
  mesh term: Anastrozole
  mesh term: Exemestane
  sharing ipd: Yes
  ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: Data can be shared no earlier than 1 year following the date of publication
  ipd access criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu