<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/NCT04498793</url>
  </required_header>
  <id_info>
    <org_study_id>NCC2474</org_study_id>
    <nct_id>NCT04498793</nct_id>
  </id_info>
  <brief_title>Study of Tislelizumab Plus Chemotherapy vs Chemotherapy as Perioperative Treatment in Participants With HER2 Negative Breast Cancer</brief_title>
  <official_title>Study of Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as Perioperative Treatment in Participants With HER2 Negative 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>First Affiliated Hospital Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wuhan Union Hospital, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Huanxing Cancer Hospital</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 study is to evaluate the efficacy and safety of tislelizumab plus&#xD;
      chemotherapy vs chemotherapy alone as perioperative treatment in participants who have triple&#xD;
      negative HER2 negative breast cancer.&#xD;
&#xD;
      After a screening phase of approximately 28 days, each participant will receive neoadjuvant&#xD;
      study treatment (Tislelizumab + Chemotherapy OR Chemotherapy) based on the randomization&#xD;
      schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive&#xD;
      surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment.&#xD;
&#xD;
      After definitive surgery, each participant will receive adjuvant study treatment (routine&#xD;
      adjuvant treatment +/- Tislelizumab) for approximately 42 weeks (14 cycles).&#xD;
&#xD;
      Following adjuvant study treatment, each participant will be monitored for safety, survival&#xD;
      and disease recurrence.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery</measure>
    <time_frame>Up to 30 weeks</time_frame>
    <description>pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>HER2-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>PD-1 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive tislelizumab every 3 weeks (Q3W) + nab-paclitaxel weekly x 4 cycles, followed by tislelizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 14 cycles of tislelizumab Q3W plus capecitabine (TNBC subtype) or endocrine therapy (Luminal subtype) as adjuvant therapy post-surgery.&#xD;
Each cycle is 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive nab-paclitaxel weekly x 4 cycles followed by (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by capecitabine (TNBC subtype) or endocrine therapy (Luminal subtype) as adjuvant therapy post-surgery.&#xD;
Each cycle is 21 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tislelizumab</intervention_name>
    <description>On Day 1 of the last seven cycles in the neoadjuvant and each cycle in the adjuvant phases of the study for a total of 21 cycles; intravenous (IV) infusion.</description>
    <arm_group_label>PD-1 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab paclitaxel</intervention_name>
    <description>On Days 1 and 8 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>PD-1 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>PD-1 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>PD-1 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>PD-1 group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically proven diagnosis of invasive breast cancer, cT1-T3, cN0-N3, cM0, HR+&#xD;
             (ER+ and/or PR+) HER2 negative or HR- (ER- and PR-) HER2 negative/triple negative&#xD;
             breast cancer.&#xD;
&#xD;
          -  Provides a core needle biopsy consisting of at least 2 separate tumor cores from the&#xD;
             primary tumor at screening to the central laboratory.&#xD;
&#xD;
          -  Immune active subtype revealed by multiplexed&#xD;
&#xD;
          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed&#xD;
             within 10 days of treatment initiation.&#xD;
&#xD;
          -  Demonstrates adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of invasive malignancy ≤5 years prior to signing informed consent except&#xD;
             for adequately treated basal cell or squamous cell skin cancer or in situ cervical&#xD;
             cancer.&#xD;
&#xD;
          -  Has received prior chemotherapy, targeted therapy, or radiation therapy for breast&#xD;
             cancer.&#xD;
&#xD;
          -  Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),&#xD;
             anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent&#xD;
             directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in past 2 years&#xD;
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs).&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e.&#xD;
             dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study treatment.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
          -  Has known active Hepatitis B or Hepatitis C.&#xD;
&#xD;
          -  Has a known history of active tuberculosis.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has significant cardiovascular disease, such as: history of myocardial infarction,&#xD;
             acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the&#xD;
             last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA)&#xD;
             Class II-IV or history of CHF NYHA Class III or IV.&#xD;
&#xD;
          -  Pregnant or lactating women are ineligible.&#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_contact>
    <last_name>Hongnan Mo</last_name>
    <phone>+861087788120</phone>
    <email>mhnzlyynk@outlook.com</email>
  </overall_contact>
  <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>
    <facility>
      <name>Beijing Huanxing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 3, 2020</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>Principal Investigator</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>Paclitaxel</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Tislelizumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04498793
org study id: NCC2474
nct id: NCT04498793
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of tislelizumab plus
      chemotherapy vs chemotherapy alone as perioperative treatment in participants who have triple
      negative HER2 negative breast cancer.

      After a screening phase of approximately 28 days, each participant will receive neoadjuvant
      study treatment (Tislelizumab + Chemotherapy OR Chemotherapy) based on the randomization
      schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive
      surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment.

      After definitive surgery, each participant will receive adjuvant study treatment (routine
      adjuvant treatment +/- Tislelizumab) for approximately 42 weeks (14 cycles).

      Following adjuvant study treatment, each participant will be monitored for safety, survival
      and disease recurrence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
time frame: Up to 30 weeks
description: pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
arm group label: PD-1 group
arm group type: Experimental
description: Participants receive tislelizumab every 3 weeks (Q3W) + nab-paclitaxel weekly x 4 cycles, followed by tislelizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 14 cycles of tislelizumab Q3W plus capecitabine (TNBC subtype) or endocrine therapy (Luminal subtype) as adjuvant therapy post-surgery.
Each cycle is 21 days.
arm group label: Control group
arm group type: Active Comparator
description: Participants receive nab-paclitaxel weekly x 4 cycles followed by (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by capecitabine (TNBC subtype) or endocrine therapy (Luminal subtype) as adjuvant therapy post-surgery.
Each cycle is 21 days.
intervention type: Biological
intervention name: Tislelizumab
description: On Day 1 of the last seven cycles in the neoadjuvant and each cycle in the adjuvant phases of the study for a total of 21 cycles; intravenous (IV) infusion.
arm group label: PD-1 group
intervention type: Drug
intervention name: Nab paclitaxel
description: On Days 1 and 8 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
arm group label: Control group
arm group label: PD-1 group
intervention type: Drug
intervention name: Doxorubicin
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
arm group label: Control group
arm group label: PD-1 group
intervention type: Drug
intervention name: Epirubicin
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
arm group label: Control group
arm group label: PD-1 group
intervention type: Device
intervention name: Cyclophosphamide
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
arm group label: Control group
arm group label: PD-1 group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hongnan Mo
phone: +861087788120
email: mhnzlyynk@outlook.com
facility: 
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: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Epirubicin
mesh term: Tislelizumab