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/NCT05983094</url>
    </required_header>
    <id_info>
      <org_study_id>NCC4047</org_study_id>
      <nct_id>NCT05983094</nct_id>
    </id_info>
    <brief_title>Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer</brief_title>
    <official_title>Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Chinese Academy of Medical Sciences Cancer Hospital，Shanxi Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Chinese Academy of Medical Sciences Cancer Hospital，Shenzhen Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>First Affiliated Hospital of China Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this clinical trial is to evaluate the efficacy and safety of Utidelone based&#xD;
        regimen as neoadjuvant treatment With High-risk Early-stage or Locally Advanced Breast&#xD;
        Cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single arm, multi-center study,three-cohort, prospective phase II study which will&#xD;
        enroll 181 high-risk early-stage or locally advanced breast cancer patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 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>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Study of Utidelone based neoadjuvant treatment on early high-risk or locally advanced breast cancer</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Total pathological complete response (etpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is, (yp)N0)</measure>
      <time_frame>24 months</time_frame>
      <description>Percentage of patients with absence of invasive neoplastic cells in ipsilateral lymph nodes and breast</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Breast Pathologic Complete Response ((bpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is)</measure>
      <time_frame>24 months</time_frame>
      <description>Percentage of patients whose pathological evaluation of hematoxylin and eosin-stained breast samples do not show any residual invasive carcinoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event Free Survival(EFS) of 2 years</measure>
      <time_frame>24 months</time_frame>
      <description>Time from the first dose of study intervention administration to any of the following events: progression of disease that precludes surgery, local or distant recurrence after surgery, second primary malignancy (breast or other invasive cancers), or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>Graded according to the Common Terminology Criteria for Adverse Event (CTCAE) grade and changes in CTCAE grade</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcome (PRO)</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life；The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcome (PRO)</measure>
      <time_frame>Through study completion，an average of 1 year</time_frame>
      <description>The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-chemotherapy-induced peripheral neuropathy(CIPN) twenty-item scale (QLQ-CIPN20) was used to assess the quality of life.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">181</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Neoadjuvant Therapy</condition>
    <arm_group>
      <arm_group_label>cohort 1 Triple-negative breast cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Hormone Receptor(HR) negative, Human Epidermal Growth Factor Receptor 2(HER2 )negative breast cancer Drug: Utidelone in combination with carboplatin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin ,Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>cohort 2 HR positive, HER2 negative breast cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HR positive, HER2 negative, Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ hybridization(FISH)non-amplification breast cancer Drug: Utidelone in combination with Epirubicin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Epirubicin 75mg/m2 was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: Utidelone in combination with carboplatin, trastuzumab and pertuzumab Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total. Trastuzumab 8mg/kg iv in first cycle on day 1, then 8mg/kg in the rest cycles; pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles.&#xD;
  One treatment cycle is 21 days, and there are 6 cycles in total.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Utidelone</intervention_name>
      <description>Utidelone injection 30mg/m2, on days 1-5 of each cycle</description>
      <arm_group_label>cohort 1 Triple-negative breast cancer</arm_group_label>
      <arm_group_label>cohort 2 HR positive, HER2 negative breast cancer</arm_group_label>
      <arm_group_label>cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>Carboplatin Area under curve(AUC)6, iv, was administered on day 1</description>
      <arm_group_label>cohort 1 Triple-negative breast cancer</arm_group_label>
      <arm_group_label>cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Epirubicin</intervention_name>
      <description>Epirubicin 75mg/m2 was administered on day 1</description>
      <arm_group_label>cohort 2 HR positive, HER2 negative breast cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trastuzumab</intervention_name>
      <description>Trastuzumab 8mg/kg iv in first cycle on day 1, then 6mg/kg in the rest cycles</description>
      <arm_group_label>cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pertuzumab</intervention_name>
      <description>Pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles</description>
      <arm_group_label>cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Female patients who will receive initial treatment, 18-70 years of age；&#xD;
  &#xD;
            2. Newly diagnosed high-risk early stage (T1c-2, N1; T2, N0) and locally advanced (T1c-2,&#xD;
               N2-3; T3-4, N0-3) breast cancer (tumor stage II, III), in which HR+/HER2- T2, N0&#xD;
               patients need to be accompanied by high-risk factors (histological grade 3 or Ki67 ≥&#xD;
               20%). Triple negative breast cancer(TNBC), HER2 positive (Immunohistochemical(IHC)3+;&#xD;
               IHC 2+, FISH amplification) breast cancer, HR negative HER2 IHC 2+ and undetermined&#xD;
               result of FISH, HR positive HER2 negative (IHC 0,1+; 2+, FISH amplification) breast&#xD;
               cancer confirmed by pathological test.&#xD;
  &#xD;
            3. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1&#xD;
  &#xD;
            4. The blood routine examination was basically normal (CTCAE ≤ 1) within one week before&#xD;
               enrollment (based on the normal values of each research center laboratory). No Human&#xD;
               Granulocyte Colony Stimulating Factor(rhGCSF) or blood transfusion/erythropoietin(EPO)&#xD;
               or other drugs were used within 14 days prior to enrollment.&#xD;
  &#xD;
               White blood cell count (WBC) ≥ 4 x109 / L; Neutrophil count (ANC) &gt; 1.5x109 / L;&#xD;
               Platelet count (PLT) ≥ 100×109/L Hemoglobin(Hb) ≥ 100g/L.&#xD;
  &#xD;
            5. The blood biochemistry examination was basically normal (CTCAE ≤ 1) within one week&#xD;
               before enrollment (based on the normal values of each research center laboratory)&#xD;
               Serum total bilirubin ≤ Upper limit of normal value(ULN)； Aspartate aminotransferase&#xD;
               (AST) and Alanine aminotransferase (ALT) ≤ 1.5×ULN； Alkaline phosphatase ≤ 2.5×ULN；&#xD;
               Serum creatinine ≤ 1.5×ULN.&#xD;
  &#xD;
            6. Color Doppler echocardiography left ventricular Ejection fraction (LVEF) ≥ 55%&#xD;
  &#xD;
            7. Female patients with fertility must agree to use effective contraceptive methods&#xD;
               during the study period and within 6 months of the last study medication. The&#xD;
               Pregnancy test (urine or serum) must be negative&#xD;
  &#xD;
            8. Be willing and able to provide written informed consent/assent for the trial.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Primary stage IV breast cancer；&#xD;
  &#xD;
            2. Inflammatory breast cancer;&#xD;
  &#xD;
            3. Bilateral primary breast cancer (including invasive cancer and carcinoma in situ)；&#xD;
  &#xD;
            4. Previous anti-cancer treatment or radiotherapy for any malignant tumor, excluding&#xD;
               cured cervical Carcinoma in situ, skin Basal-cell carcinoma and squamous cell&#xD;
               carcinoma.&#xD;
  &#xD;
            5. Receive any sex hormone treatment (such as contraceptives, ovarian hormone replacement&#xD;
               therapy, etc.), except for Ovarian function suppression（OFS）fertility protection, or&#xD;
               any hormone drugs (such as Raloxifene, tamoxifen, or other selective estrogen receptor&#xD;
               modulators) to treat osteoporosis or prevent breast cancer；&#xD;
  &#xD;
            6. The patient has undergone major surgery unrelated to breast cancer within 4 weeks&#xD;
               before treatment or has not yet fully recovered;&#xD;
  &#xD;
            7. Symptomatic peripheral neuropathy CTCAE 5.0 grade ≥ 2&#xD;
  &#xD;
            8. Serious cardio cerebral Vascular disease, including but not limited to the followings:&#xD;
  &#xD;
            9. History of congestive heart failure or systolic dysfunction (LVEF&lt;50%);&#xD;
  &#xD;
           10. Angina pectoris requiring anti angina drugs;&#xD;
  &#xD;
           11. High risk uncontrolled arrhythmias or severe conduction abnormalities, such as&#xD;
               ventricular arrhythmias that require clinical intervention, II-III degree&#xD;
               atrioventricular block, etc; Under resting state, the average corrected Q-T&#xD;
               interval(QTcF) of three 12 lead electrocardiogram examinations is&gt;470ms;&#xD;
  &#xD;
           12. Clinically significant heart valve disease with cardiac dysfunction;&#xD;
  &#xD;
           13. Hypertension that cannot be controlled;&#xD;
  &#xD;
           14. History of myocardial infarction&#xD;
  &#xD;
           15. Allergic to any component of any drug in this protocol.&#xD;
  &#xD;
           16. Those who are not suitable for using Corticosteroid.&#xD;
  &#xD;
           17. Individuals with active infections who currently require systematic anti infection&#xD;
               treatment.&#xD;
  &#xD;
           18. History of immune deficiency disease, including positive of HIV/AIDS, or other&#xD;
               acquired or congenital immune deficiency diseases, or having a history of organ&#xD;
               transplantation.&#xD;
  &#xD;
           19. Who had participated in other drug intervention clinical trials within the 28 days of&#xD;
               randomization, or who is participating in another clinical trial or is using other&#xD;
               investigational treatments.&#xD;
  &#xD;
           20. Individuals in pregnancy (positive Pregnancy test) and lactation.&#xD;
  &#xD;
           21. Any other comorbidities that interfere with the implementation of the treatment plan,&#xD;
               or the researcher evaluate that the subject has a history of other serious systemic&#xD;
               diseases, or other reasons lead to the patients is unsuitable to participate in this&#xD;
               trial.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Cancer Hospital, Chinese Academy of Medical Sciences</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100021</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
      <investigator_full_name>Ma Fei，MD</investigator_full_name>
      <investigator_title>Deputy Director of the Department of Medical Oncology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>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/NCT05983094
  org study id: NCC4047
  nct id: NCT05983094
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this clinical trial is to evaluate the efficacy and safety of Utidelone based
        regimen as neoadjuvant treatment With High-risk Early-stage or Locally Advanced Breast
        Cancer.
  This is a single arm, multi-center study,three-cohort, prospective phase II study which will
        enroll 181 high-risk early-stage or locally advanced breast cancer patients.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Study of Utidelone based neoadjuvant treatment on early high-risk or locally advanced breast cancer
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Total pathological complete response (etpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is, (yp)N0)
  time frame: 24 months
  description: Percentage of patients with absence of invasive neoplastic cells in ipsilateral lymph nodes and breast
  measure: Breast Pathologic Complete Response ((bpCR, Pathologic staging after neoadjuvant therapy(yp)T0/is)
  time frame: 24 months
  description: Percentage of patients whose pathological evaluation of hematoxylin and eosin-stained breast samples do not show any residual invasive carcinoma
  measure: Event Free Survival(EFS) of 2 years
  time frame: 24 months
  description: Time from the first dose of study intervention administration to any of the following events: progression of disease that precludes surgery, local or distant recurrence after surgery, second primary malignancy (breast or other invasive cancers), or death due to any cause.
  measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
  time frame: Through study completion，an average of 1 year
  description: Graded according to the Common Terminology Criteria for Adverse Event (CTCAE) grade and changes in CTCAE grade
  measure: Patient reported outcome (PRO)
  time frame: Through study completion，an average of 1 year
  description: National Cancer Center of China-Breast Cancer-A 1.0 (NCC-BC-A 1.0) during the study was used to assess the quality of life；The minimum to maximum values: 0 , 100 Meaning: the higher scores mean a better outcome.
  measure: Patient reported outcome (PRO)
  time frame: Through study completion，an average of 1 year
  description: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-chemotherapy-induced peripheral neuropathy(CIPN) twenty-item scale (QLQ-CIPN20) was used to assess the quality of life.
  arm group label: cohort 1 Triple-negative breast cancer
  arm group type: Experimental
  description: Hormone Receptor(HR) negative, Human Epidermal Growth Factor Receptor 2(HER2 )negative breast cancer Drug: Utidelone in combination with carboplatin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin ,Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.
  arm group label: cohort 2 HR positive, HER2 negative breast cancer
  arm group type: Experimental
  description: HR positive, HER2 negative, Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situ hybridization(FISH)non-amplification breast cancer Drug: Utidelone in combination with Epirubicin Utidelone injection 30mg/m2, on days 1-5 of each cycle; Epirubicin 75mg/m2 was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total.
  arm group label: cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
  arm group type: Experimental
  description: Drug: Utidelone in combination with carboplatin, trastuzumab and pertuzumab Utidelone injection 30mg/m2, on days 1-5 of each cycle; Carboplatin Area Under Curve(AUC)6, iv, was administered on day 1; One treatment cycle is 21 days, and there are 6 cycles in total. Trastuzumab 8mg/kg iv in first cycle on day 1, then 8mg/kg in the rest cycles; pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles.
  One treatment cycle is 21 days, and there are 6 cycles in total.
  intervention type: Drug
  intervention name: Utidelone
  description: Utidelone injection 30mg/m2, on days 1-5 of each cycle
  arm group label: cohort 1 Triple-negative breast cancer
  arm group label: cohort 2 HR positive, HER2 negative breast cancer
  arm group label: cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
  intervention type: Drug
  intervention name: Carboplatin
  description: Carboplatin Area under curve(AUC)6, iv, was administered on day 1
  arm group label: cohort 1 Triple-negative breast cancer
  arm group label: cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
  intervention type: Drug
  intervention name: Epirubicin
  description: Epirubicin 75mg/m2 was administered on day 1
  arm group label: cohort 2 HR positive, HER2 negative breast cancer
  intervention type: Drug
  intervention name: Trastuzumab
  description: Trastuzumab 8mg/kg iv in first cycle on day 1, then 6mg/kg in the rest cycles
  arm group label: cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
  intervention type: Drug
  intervention name: Pertuzumab
  description: Pertuzumab 840mg/kg iv in first cycle on day 1, then 420mg/kg in the rest cycles
  arm group label: cohort 3 HER2 positive (IHC 3+; IHC 2+,FISH amplification) breast cancer
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  investigator full name: Ma Fei，MD
  investigator title: Deputy Director of the Department of Medical Oncology
  mesh term: Breast Neoplasms
  mesh term: Carboplatin
  mesh term: Trastuzumab
  mesh term: Epirubicin
  mesh term: Pertuzumab