<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/NCT04418154</url>
  </required_header>
  <id_info>
    <org_study_id>SCHBCC-NO27</org_study_id>
    <nct_id>NCT04418154</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Dose-dense EC Followed by ABX With PD-1 for Triple Negative Breast Cancer Patients</brief_title>
  <official_title>Dose-dense Epirubicin Hydrochloride With Cyclophosphamide Followed by Nanoparticlealbumin-bound Paclitaxel With PD-1 Regimen in Neoadjuvant Therapy for Patients With Triple-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</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>
      This study is to evaluate the efficacy and safety for dose-dense epirubicin hydrochloride&#xD;
      with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 in&#xD;
      neoadjuvant therapy for patients with triple-negative breast cancer, and to explore the&#xD;
      predictive value of biological markers for the treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open single arm study, which would undergo optimal two stage designs. 60&#xD;
      patients who are diagnosed with triple-negative breast cancer would have dose-dense&#xD;
      epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound&#xD;
      paclitaxel with PD-1 regimen for neoadjuvant therapy if they meet the eligibility criteria.&#xD;
      The regimen is as follows: epirubicin hydrochloride (90mg/m2, d1) plus cyclophosphamide&#xD;
      (600mg/m2, d1) every 14 days as one cycle for 4 cycles, followed by nanoparticlealbumin-bound&#xD;
      paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles, and Toripalimab&#xD;
      (240mg, d1) every 3 weeks as one cycle for 4 cycles. pathological complete response would be&#xD;
      the primary endpoint. The change of biological markers and safety of the regimen would also&#xD;
      be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">September 1, 2022</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>Pathologic complete response (pCR)</measure>
    <time_frame>Immediately after the surgery</time_frame>
    <description>Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in tumor-infiltrating lymphocytes (TILs)</measure>
    <time_frame>before the first neoadjuvant chemotherapy (baseline), at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining. TILs in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), right before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in programmed cell death protein 1 (PD1)</measure>
    <time_frame>at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in programmed cell death ligand 1 (PD-L1)</measure>
    <time_frame>at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>PD-L1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD-L1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in androgen receptor (AR)</measure>
    <time_frame>at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>AR in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. AR in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cluster of differentiation 8 (CD8)</measure>
    <time_frame>at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. CD8 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in recombinant forkhead box protein C1 (FOXC1)</measure>
    <time_frame>at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery</time_frame>
    <description>FOXC1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. FOXC1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Immediately after the surgery</time_frame>
    <description>Defined as the percentage of cases obtaining complete remission and partial response in all evaluable cases.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of breast-conserving surgery</measure>
    <time_frame>Immediately after the surgery</time_frame>
    <description>Defined as the percentage of patients who have breast-conserving surgery in all evaluable patients.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>EC-ABX/PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who are treated with epirubicin hydrochloride andcyclophosphamide followed by nanoparticlealbumin-bound paclitaxel and Toripalimab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>epirubicin hydrochloride</intervention_name>
    <description>Take epirubicin hydrochloride (90mg/m2, d1) every 14 days as one cycle for 4 cycles with cyclophosphamide, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.</description>
    <arm_group_label>EC-ABX/PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Take cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles with epirubicin hydrochloride, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.</description>
    <arm_group_label>EC-ABX/PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albumin bound paclitaxel</intervention_name>
    <description>Take nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles with Toripalimab, following epirubicin hydrochloride and cyclophosphamide.</description>
    <arm_group_label>EC-ABX/PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Take Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles with nanoparticlealbumin-bound paclitaxel, following epirubicin hydrochloride and cyclophosphamide.</description>
    <arm_group_label>EC-ABX/PD-1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female between 18 to 70 years old.&#xD;
&#xD;
          -  Patients be diagnosed with primary unilateral invasive breast cancer of cT2-4NanyM0 by&#xD;
             histology.&#xD;
&#xD;
          -  Patients with ER negative and PR negative by immunohistochemistry (IHC), and HER-2&#xD;
             negative disease. HER2-negative disease was defined as follows: disease whose HER-2 is&#xD;
             1+ or negative by IHC, or fluorescence in situ hybridization (FISH) is negative if IHC&#xD;
             is 2+.&#xD;
&#xD;
          -  At least one mensurable objective focus according to RECIST guideline (vision 1.1).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status is less than or equal to&#xD;
             (&lt;/=) 1.&#xD;
&#xD;
          -  Baseline left ventricular ejection fraction (LVEF) is greater than or equal to (&gt;/=)&#xD;
             55%.&#xD;
&#xD;
          -  Bone marrow function is required as follows: neutrophils are more than or equal to&#xD;
             (&gt;/=) 1.5×109/L, platelets more than or equal to (&gt;/=) 100×109/L, and hemoglobin more&#xD;
             than or equal to (&gt;/=) 90g/L.&#xD;
&#xD;
          -  Hepatic and renal function are required as follows: serum creatinine is less than or&#xD;
             equal to (&lt;/=) 1.5 times of upper limits of normal (ULN), aspartate transaminase (AST)&#xD;
             and alanine aminotransferase (ALT) less than or equal to (&lt;/=) 2.5 times of ULN, and&#xD;
             total bilirubin less than or equal to (&lt;/=) 1.5 times of ULN or &lt;/= 2.5 times of ULN&#xD;
             if patient is with Gilbert's syndrome.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Able to comply with the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received any previous therapy including cytotoxic chemotherapy, endocrine therapy,&#xD;
             biological therapy or radiation therapy for any reason.&#xD;
&#xD;
          -  Patients with heart disease whose New York Heart Association class (NYHA) is higher or&#xD;
             equal to (&gt;/=) Class II.&#xD;
&#xD;
          -  Severe systemic infection or with other severe disease.&#xD;
&#xD;
          -  Known hypersensitivity to any of the study drugs or excipients.&#xD;
&#xD;
          -  Previous non-breast malignancy within 5 years prior to study entry excluding healed&#xD;
             cervical carcinoma in situ and non-melanoma skin cancer.&#xD;
&#xD;
          -  Pregnancy, breast-feeding or child-bearing women who refuse contraception during the&#xD;
             trial.&#xD;
&#xD;
          -  Participants who received any other investigational treatment within 30 days before&#xD;
             the first dose of drug investigated.&#xD;
&#xD;
          -  Patients who are inconformity to participate in this study according to investigators.&#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>Shanghai Cancer Center, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>July 4, 2023</last_update_submitted>
  <last_update_submitted_qc>July 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Jiong Wu</investigator_full_name>
    <investigator_title>Professor, Department of Breast Surgery Vice President, Cancer Hospital, Fudan University</investigator_title>
  </responsible_party>
  <keyword>Programmed Death-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative 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>Cyclophosphamide</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04418154
org study id: SCHBCC-NO27
nct id: NCT04418154
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is to evaluate the efficacy and safety for dose-dense epirubicin hydrochloride
      with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 in
      neoadjuvant therapy for patients with triple-negative breast cancer, and to explore the
      predictive value of biological markers for the treatment.
This study is an open single arm study, which would undergo optimal two stage designs. 60
      patients who are diagnosed with triple-negative breast cancer would have dose-dense
      epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound
      paclitaxel with PD-1 regimen for neoadjuvant therapy if they meet the eligibility criteria.
      The regimen is as follows: epirubicin hydrochloride (90mg/m2, d1) plus cyclophosphamide
      (600mg/m2, d1) every 14 days as one cycle for 4 cycles, followed by nanoparticlealbumin-bound
      paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles, and Toripalimab
      (240mg, d1) every 3 weeks as one cycle for 4 cycles. pathological complete response would be
      the primary endpoint. The change of biological markers and safety of the regimen would also
      be evaluated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic complete response (pCR)
time frame: Immediately after the surgery
description: Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.
measure: Change in tumor-infiltrating lymphocytes (TILs)
time frame: before the first neoadjuvant chemotherapy (baseline), at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining. TILs in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), right before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Change in programmed cell death protein 1 (PD1)
time frame: at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Change in programmed cell death ligand 1 (PD-L1)
time frame: at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: PD-L1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD-L1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Change in androgen receptor (AR)
time frame: at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: AR in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. AR in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Change in cluster of differentiation 8 (CD8)
time frame: at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. CD8 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Change in recombinant forkhead box protein C1 (FOXC1)
time frame: at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery
description: FOXC1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. FOXC1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.
measure: Objective response rate (ORR)
time frame: Immediately after the surgery
description: Defined as the percentage of cases obtaining complete remission and partial response in all evaluable cases.
measure: Rate of breast-conserving surgery
time frame: Immediately after the surgery
description: Defined as the percentage of patients who have breast-conserving surgery in all evaluable patients.
arm group label: EC-ABX/PD-1
arm group type: Experimental
description: Patients who are treated with epirubicin hydrochloride andcyclophosphamide followed by nanoparticlealbumin-bound paclitaxel and Toripalimab
intervention type: Drug
intervention name: epirubicin hydrochloride
description: Take epirubicin hydrochloride (90mg/m2, d1) every 14 days as one cycle for 4 cycles with cyclophosphamide, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.
arm group label: EC-ABX/PD-1
intervention type: Drug
intervention name: Cyclophosphamide
description: Take cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles with epirubicin hydrochloride, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.
arm group label: EC-ABX/PD-1
intervention type: Drug
intervention name: Albumin bound paclitaxel
description: Take nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles with Toripalimab, following epirubicin hydrochloride and cyclophosphamide.
arm group label: EC-ABX/PD-1
intervention type: Drug
intervention name: Toripalimab
description: Take Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles with nanoparticlealbumin-bound paclitaxel, following epirubicin hydrochloride and cyclophosphamide.
arm group label: EC-ABX/PD-1
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Jiong Wu
investigator title: Professor, Department of Breast Surgery Vice President, Cancer Hospital, Fudan University
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Epirubicin
mesh term: Albumin-Bound Paclitaxel
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code