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/NCT05978648</url>
    </required_header>
    <id_info>
      <org_study_id>SMA-BC-002</org_study_id>
      <nct_id>NCT05978648</nct_id>
    </id_info>
    <brief_title>Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy</brief_title>
    <acronym>SMA-BC-002</acronym>
    <official_title>A Prospective, Multi-cohort, Exploratory Phase II Study of Trilaciclib Combined With Standard Chemotherapy in The Adjuvant Treatment of Hormone Receptor (HR) Negative Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>wang shusen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sun Yat-sen University</source>
    <oversight_info>
      <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>
        The goal of this multicenter, two-cohort, exploratory clinical trial is to evaluate patients&#xD;
        with early stage hormone receptor-negative breast cancer receiving standard adjuvant&#xD;
        chemotherapy after surgery. The main question it aims to answer is:&#xD;
  &#xD;
        • The efficacy and safety of trilaciclib administered before standard adjuvant chemotherapy&#xD;
        regimen using the incidence of grade 3/4 neutropenia as the primary efficacy endpoint.&#xD;
  &#xD;
        Participants will divide into two treatment cohorts according to molecular typing type:&#xD;
  &#xD;
          -  Cohort A will be planned to include post-operative triple-negative breast cancer(TNBC)&#xD;
             patients with lymph node positive or tumor &gt; 2 cm treated with trilaciclib combined with&#xD;
             epirubicin and cyclophosphamide followed by weekly paclitaxel;&#xD;
  &#xD;
          -  Cohort B will be planned to include HER2-positive/HR-negative breast cancer patients&#xD;
             with axillary node positive or tumor &gt; 2 cm treated with trilaciclib combined with&#xD;
             docetaxel, carboplatin and trastuzumab with or without pertuzumab.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Occurrence of Grade 3/4 neutropenia</measure>
      <time_frame>Up to 24 weeks</time_frame>
      <description>Proportion of subjects with at least one absolute neutrophil count (ANC) &lt; 1.0 × 10^9/L enrolled and treated with at least one dose of trilaciclib</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Neutrophil-related myeloprotective effects</measure>
      <time_frame>Up to 24 weeks</time_frame>
      <description>Occurrence of febrile neutropenia adverse events(AEs) , and occurrence of Granulocyte colony-stimulating factor(G-CSF) administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Red blood cell(RBC) -related myeloprotective effects</measure>
      <time_frame>Up to 24 weeks</time_frame>
      <description>Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5, and occurrence of erythropoiesis-stimulating agent(ESA) administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Platelet-related myeloprotective effects</measure>
      <time_frame>Up to 24 weeks</time_frame>
      <description>Occurrence of Grade 3/4 decrease of platelets, occurrence and number of platelet transfusions, and occurrence of rhTPO/Recombinant human interleukin-11(rhIL-11) administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Myeloprotective Effects</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Hospitalization due to chemotherapy-induced myelosuppression, dose reductions and delays, relative dose intensity(RDI) of chemotherapeutic agents</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Incidence of Treatment-Emergent Adverse Events as per CTCAE version 5.0</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">116</enrollment>
    <condition>Breast Neoplasms</condition>
    <arm_group>
      <arm_group_label>Cohort A: Triple-negative Breast Cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cohort A Administered Trilaciclib in Combination with Chemotherapy(EC-wP)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cohort B Administered Trilaciclib in Combination with Chemotherapy(TCbH±P)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trilaciclib</intervention_name>
      <description>240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day</description>
      <arm_group_label>Cohort A: Triple-negative Breast Cancer</arm_group_label>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
      <other_name>COSELA®</other_name>
      <other_name>G1T28</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Epirubicin</intervention_name>
      <description>90 mg/m2, intravenous drip, d1, Q3W, 4 cycles.</description>
      <arm_group_label>Cohort A: Triple-negative Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>600 mg/m2, intravenous drip, d1, Q3W, 4 cycles.</description>
      <arm_group_label>Cohort A: Triple-negative Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Paclitaxel</intervention_name>
      <description>80 mg/m2, intravenous drip, d1,8,15, Q3W, 4 cycles.</description>
      <arm_group_label>Cohort A: Triple-negative Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Docetaxel</intervention_name>
      <description>75 mg/m2, intravenous drip, d1, Q3W, 6 cycles.</description>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>area under curve(AUC) = 6, intravenous drip, d1, Q3W, 6 cycles.</description>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trastuzumab</intervention_name>
      <description>8 mg/kg in Cycle 1, 6 mg/kg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.</description>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pertuzumab</intervention_name>
      <description>840mg in Cycle 1, 420mg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.</description>
      <arm_group_label>Cohort B: ER-negative PR-negative Her2-positive Breast Cancer</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  age ≥ 18 years;&#xD;
  &#xD;
            -  breast cancer meets the following criteria:&#xD;
  &#xD;
                 -  Histologically or cytologically confirmed and adequately resected non-metastatic&#xD;
                    primary invasive breast cancer;&#xD;
  &#xD;
                 -  Cohort A only: ER, PR negative (&lt; 1% nuclear staining as assessed by&#xD;
                    immunohistochemistry [IHC]), HER2 negative (HER2/CEP17 ratio &lt; 2.0 or mean HER2&#xD;
                    gene copy number &lt; 4 signals/nucleus detected by IHC 0 or 1 + or in situ&#xD;
                    hybridization [ISH]); patients with concurrent bilateral invasive disease met the&#xD;
                    inclusion criteria if both lesions were HR negative/HER2 negative.&#xD;
  &#xD;
                 -  Cohort B only: ER, PR negative (&lt; 1% nuclear staining as assessed by&#xD;
                    immunohistochemistry [IHC]); HER2 positive: HER2/CEP17 ratio ≥ 2.0 or HER2 gene&#xD;
                    copy number ≥ 4 signals/nucleus detected by IHC 3 + and ISH; HER2 gene copy&#xD;
                    number ≥ 6 signals/nucleus detected by IHC 3 + or 2 + and ISH); patients with&#xD;
                    concurrent bilateral invasive disease met the inclusion criteria if both lesions&#xD;
                    were HR negative/HER2 positive.&#xD;
  &#xD;
                 -  Subjects must have positive lymph nodes or tumors &gt; 2 cm;&#xD;
  &#xD;
                 -  The interval between radical surgery and the first dose ≤ 60 days;&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance score 0-1;&#xD;
  &#xD;
            -  have appropriate organ function, meet the following criteria: (1) have appropriate&#xD;
               bone marrow function: Hb ≥ 100 g/L (no ESA and blood transfusion within 14 days before&#xD;
               the first dose); absolute neutrophil count (ANC) ≥ 2 × 10^9/L (no G-CSF within 14 days&#xD;
               before the first dose); platelet count ≥ 100 × 10^9/L (no rhTPO/rhIL-11 and platelet&#xD;
               transfusion within 14 days before the first dose); (2) appropriate liver and kidney&#xD;
               function: alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN),&#xD;
               aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN,&#xD;
               serum creatinine ≤ 1.5 × ULN, endogenous creatinine clearance &gt; 50 ml/min&#xD;
               (Cockcroft-Gault formula); (3) appropriate cardiac function: left ventricular ejection&#xD;
               fraction (LVEF) ≥ 55%;&#xD;
  &#xD;
            -  Non-hematologic toxicities from prior surgical procedures recovered to ≤ Grade 1 or&#xD;
               baseline (except alopecia);&#xD;
  &#xD;
            -  Females of childbearing potential agree to practice reliable contraception during the&#xD;
               clinical trial and have a negative serum or urine pregnancy test within 7 days prior&#xD;
               to dosing;&#xD;
  &#xD;
            -  Voluntarily join this study and sign informed consent, have good compliance and are&#xD;
               willing to cooperate with follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior neoadjuvant therapy (including chemotherapy, targeted therapy, immunotherapy, or&#xD;
               radiotherapy);&#xD;
  &#xD;
            -  History of other malignancy within 5 years prior to first dose, except basal cell&#xD;
               carcinoma and cervical carcinoma in situ;&#xD;
  &#xD;
            -  Any T4 or N2 or known N3 or M1 breast cancer;&#xD;
  &#xD;
            -  Subjects who cannot receive or tolerate postoperative chemotherapy for various&#xD;
               reasons;&#xD;
  &#xD;
            -  Heart disease ineligible for epirubicin, docetaxel, trastuzumab/pertuzumab:&#xD;
  &#xD;
                 -  Any documented history of myocardial infarction, congestive heart failure&#xD;
  &#xD;
                 -  Angina pectoris requiring antianginal medication&#xD;
  &#xD;
                 -  Grade 3 or 4 cardiac arrhythmia (NCI CTCAEv5.0)&#xD;
  &#xD;
                 -  Clinically significant valvular heart disease;&#xD;
  &#xD;
                 -  Poorly controlled hypertension (systolic blood pressure &gt; 180 mmHg and/or&#xD;
                    diastolic blood pressure &gt; 100 mmHg)&#xD;
  &#xD;
            -  Known history of hypersensitivity to the drug components of this protocol;&#xD;
  &#xD;
            -  Any other condition that, in the opinion of the investigator, would make the patient&#xD;
               inappropriate for participation in this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Shusen Wang, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shusen Wang, MD</last_name>
      <phone>+86-13926168469</phone>
      <email>wangshs@sysucc.org.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Sun-yat sen university cancer center</name>
        <address>
          <city>Guangzhou</city>
          <state>Gangdong</state>
          <zip>510060</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>shusen wang, MD</last_name>
        <phone>+86-13926168469</phone>
        <email>wangshs@sysucc.org.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>July 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>July 30, 2023</last_update_submitted>
    <last_update_submitted_qc>July 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>wang shusen</investigator_full_name>
      <investigator_title>Director of Breast Disease Department</investigator_title>
    </responsible_party>
    <keyword>Trilaciclib; HR-Negative Breast Cancer; Adjuvant Therapy</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>Paclitaxel</mesh_term>
      <mesh_term>Docetaxel</mesh_term>
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Trastuzumab</mesh_term>
      <mesh_term>Epirubicin</mesh_term>
      <mesh_term>Pertuzumab</mesh_term>
    </intervention_browse>
    <!-- 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/NCT05978648
  org study id: SMA-BC-002
  nct id: NCT05978648
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The goal of this multicenter, two-cohort, exploratory clinical trial is to evaluate patients
        with early stage hormone receptor-negative breast cancer receiving standard adjuvant
        chemotherapy after surgery. The main question it aims to answer is:
  
        • The efficacy and safety of trilaciclib administered before standard adjuvant chemotherapy
        regimen using the incidence of grade 3/4 neutropenia as the primary efficacy endpoint.
  
        Participants will divide into two treatment cohorts according to molecular typing type:
  
          -  Cohort A will be planned to include post-operative triple-negative breast cancer(TNBC)
             patients with lymph node positive or tumor > 2 cm treated with trilaciclib combined with
             epirubicin and cyclophosphamide followed by weekly paclitaxel;
  
          -  Cohort B will be planned to include HER2-positive/HR-negative breast cancer patients
             with axillary node positive or tumor > 2 cm treated with trilaciclib combined with
             docetaxel, carboplatin and trastuzumab with or without pertuzumab.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Occurrence of Grade 3/4 neutropenia
  time frame: Up to 24 weeks
  description: Proportion of subjects with at least one absolute neutrophil count (ANC) < 1.0 × 10^9/L enrolled and treated with at least one dose of trilaciclib
  measure: Neutrophil-related myeloprotective effects
  time frame: Up to 24 weeks
  description: Occurrence of febrile neutropenia adverse events(AEs) , and occurrence of Granulocyte colony-stimulating factor(G-CSF) administration
  measure: Red blood cell(RBC) -related myeloprotective effects
  time frame: Up to 24 weeks
  description: Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5, and occurrence of erythropoiesis-stimulating agent(ESA) administration
  measure: Platelet-related myeloprotective effects
  time frame: Up to 24 weeks
  description: Occurrence of Grade 3/4 decrease of platelets, occurrence and number of platelet transfusions, and occurrence of rhTPO/Recombinant human interleukin-11(rhIL-11) administration
  measure: Myeloprotective Effects
  time frame: Up to 24 months
  description: Hospitalization due to chemotherapy-induced myelosuppression, dose reductions and delays, relative dose intensity(RDI) of chemotherapeutic agents
  measure: Safety and tolerability
  time frame: Up to 24 months
  description: Incidence of Treatment-Emergent Adverse Events as per CTCAE version 5.0
  arm group label: Cohort A: Triple-negative Breast Cancer
  arm group type: Experimental
  description: Cohort A Administered Trilaciclib in Combination with Chemotherapy(EC-wP)
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  arm group type: Experimental
  description: Cohort B Administered Trilaciclib in Combination with Chemotherapy(TCbH±P)
  intervention type: Drug
  intervention name: Trilaciclib
  description: 240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day
  arm group label: Cohort A: Triple-negative Breast Cancer
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  other name: COSELA®
  other name: G1T28
  intervention type: Drug
  intervention name: Epirubicin
  description: 90 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
  arm group label: Cohort A: Triple-negative Breast Cancer
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: 600 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
  arm group label: Cohort A: Triple-negative Breast Cancer
  intervention type: Drug
  intervention name: Paclitaxel
  description: 80 mg/m2, intravenous drip, d1,8,15, Q3W, 4 cycles.
  arm group label: Cohort A: Triple-negative Breast Cancer
  intervention type: Drug
  intervention name: Docetaxel
  description: 75 mg/m2, intravenous drip, d1, Q3W, 6 cycles.
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  intervention type: Drug
  intervention name: Carboplatin
  description: area under curve(AUC) = 6, intravenous drip, d1, Q3W, 6 cycles.
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  intervention type: Drug
  intervention name: Trastuzumab
  description: 8 mg/kg in Cycle 1, 6 mg/kg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  intervention type: Drug
  intervention name: Pertuzumab
  description: 840mg in Cycle 1, 420mg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.
  arm group label: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Shusen Wang, MD
  role: Principal Investigator
  affiliation: Sun Yat-sen University
  last name: Shusen Wang, MD
  phone: +86-13926168469
  email: wangshs@sysucc.org.cn
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: wang shusen
  investigator title: Director of Breast Disease Department
  mesh term: Breast Neoplasms
  mesh term: Paclitaxel
  mesh term: Docetaxel
  mesh term: Cyclophosphamide
  mesh term: Carboplatin
  mesh term: Trastuzumab
  mesh term: Epirubicin
  mesh term: Pertuzumab