<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/NCT04501523</url>
  </required_header>
  <id_info>
    <org_study_id>SunYatsenU2H-LQ3</org_study_id>
    <nct_id>NCT04501523</nct_id>
  </id_info>
  <brief_title>A Prospective, Phase II Trial Using ctDNA to Initiate Post-operation Boost Therapy After NAC in TNBC</brief_title>
  <acronym>Apollo</acronym>
  <official_title>A Prospective, Phase II Trial Using Circulating Tumor DNA to Initiate Post-operation Boost Therapy After Neoadjuvant Chemotherapy in Triple-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Positive circulating tumor DNA(ctDNA) status is associated with worse prognosis in breast&#xD;
      cancer, especially triple-negative breast cancer(TNBC). Our trial aims to improve the outcome&#xD;
      of TNBC patients by using ctDNA to identify patients with high relapse risk. ctDNA positive&#xD;
      patients will be randomized to receive boost therapy or standard therapy indicated in NCCN&#xD;
      guidelines after NAC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Anticipated">August 2032</completion_date>
  <primary_completion_date type="Anticipated">August 2027</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>5 years Disease free survival(DFS)</measure>
    <time_frame>60 months</time_frame>
    <description>From diagnosis to 5yrs or DFS events; To determine 5-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>5 years overall survival(OS)</measure>
    <time_frame>60 months</time_frame>
    <description>From diagnosis to 5yrs or death; To determine 5-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pathological complete remission(pCR) rate</measure>
    <time_frame>12 months</time_frame>
    <description>pathological complete remission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>brain metastasis rate</measure>
    <time_frame>60 months</time_frame>
    <description>The percentage of patients who develop brain metastasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>objective response rate(ORR)</measure>
    <time_frame>12 months</time_frame>
    <description>The percentage of patients who achieved PR+CR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>12 months</time_frame>
    <description>To determine the toxicities associated with tislelizumab in this population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>10 years DFS</measure>
    <time_frame>120 months</time_frame>
    <description>To determine 10-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>10 years OS</measure>
    <time_frame>120 months</time_frame>
    <description>To determine 10-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse and metastasis rate</measure>
    <time_frame>24 months</time_frame>
    <description>The percentage of patients who develop brain metastasis any relapse or metastasis</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">460</enrollment>
  <condition>Triple-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ctDNA positive, non-pCR Intervention: capecitabine(standard care)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ctDNA positive, pCR Intervention: capecitabine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Follow up(standard care)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tislelizumab</intervention_name>
    <description>200mg, q3w, for 1 year</description>
    <arm_group_label>A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>capecitabine</intervention_name>
    <description>600-750 mg/m2 PO Bid，continuous, for 1 year</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-)&#xD;
             invasive breast cancer, clinical stage II-III at diagnosis (AJCC 6th edition) based on&#xD;
             initial evaluation by physical examination and/or breast imaging prior to study&#xD;
             registration.ER and PR will be considered negative if ≤ 1% of cells stain weakly&#xD;
             positive. HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry&#xD;
             (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio&#xD;
             of &lt; 2.0 or &lt; 6 copies per cell.&#xD;
&#xD;
          -  Must receive preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative&#xD;
             regimens include those recommended by NCCN guidelines. Participants who received&#xD;
             preoperative therapy as part of a clinical trial may enroll.&#xD;
&#xD;
          -  ctDNA positive at baseline, after NAC or after surgery&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2&#xD;
&#xD;
          -  Written informed consent to provide research blood samples and tumor samples&#xD;
&#xD;
          -  Patients must be willing to have frequent blood tests (every 3 months ) and receive a&#xD;
             12 month course of tislelizumab if randomised to tislelizumab treatment on ctDNA&#xD;
             detection&#xD;
&#xD;
          -  No evidence of distant metastatic disease on staging scans conducted at the time of&#xD;
             diagnosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previously participated in other interventional trials&#xD;
&#xD;
          -  Previous malignancy within 3 years of breast cancer diagnosis&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  No written consent&#xD;
&#xD;
          -  Unable to receive standard NAC and subsequent radiotherapy(if needed)&#xD;
&#xD;
          -  Active autoimmune disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qiang Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunyat-sen Memorial Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shunying Li, MD</last_name>
    <phone>+86-15915939702</phone>
    <email>lishunying@foxmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yudong Li, MD</last_name>
    <phone>020-34071156</phone>
    <email>910870698@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sunyat-sen Memorial Hospital</name>
      <address>
        <city>Guandong</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>shunying Li</last_name>
      <phone>+86-15915939702</phone>
      <email>lishunying@foxmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>February 16, 2023</last_update_submitted>
  <last_update_submitted_qc>February 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Liu Qiang</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <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>Capecitabine</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/NCT04501523
org study id: SunYatsenU2H-LQ3
nct id: NCT04501523
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Positive circulating tumor DNA(ctDNA) status is associated with worse prognosis in breast
      cancer, especially triple-negative breast cancer(TNBC). Our trial aims to improve the outcome
      of TNBC patients by using ctDNA to identify patients with high relapse risk. ctDNA positive
      patients will be randomized to receive boost therapy or standard therapy indicated in NCCN
      guidelines after NAC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 5 years Disease free survival(DFS)
time frame: 60 months
description: From diagnosis to 5yrs or DFS events; To determine 5-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy
measure: 5 years overall survival(OS)
time frame: 60 months
description: From diagnosis to 5yrs or death; To determine 5-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy
measure: pathological complete remission(pCR) rate
time frame: 12 months
description: pathological complete remission
measure: brain metastasis rate
time frame: 60 months
description: The percentage of patients who develop brain metastasis
measure: objective response rate(ORR)
time frame: 12 months
description: The percentage of patients who achieved PR+CR
measure: Number of Patients with Adverse Events as a Measure of Safety and Tolerability
time frame: 12 months
description: To determine the toxicities associated with tislelizumab in this population
measure: 10 years DFS
time frame: 120 months
description: To determine 10-year disease free survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy
measure: 10 years OS
time frame: 120 months
description: To determine 10-year overall survival in ctDNA positive participants with confirmed triple negative breast cancer (TNBC) treated with a boost therapy or standard of care following preoperative chemotherapy
measure: Relapse and metastasis rate
time frame: 24 months
description: The percentage of patients who develop brain metastasis any relapse or metastasis
arm group label: A
arm group type: Experimental
description: ctDNA positive, non-pCR Intervention: Tislelizumab(anti-PD1 antibody) combined with capecitabine
arm group label: B
arm group type: Active Comparator
description: ctDNA positive, non-pCR Intervention: capecitabine(standard care)
arm group label: C
arm group type: Experimental
description: ctDNA positive, pCR Intervention: capecitabine
arm group label: D
arm group type: No Intervention
description: Follow up(standard care)
intervention type: Drug
intervention name: Tislelizumab
description: 200mg, q3w, for 1 year
arm group label: A
intervention type: Drug
intervention name: capecitabine
description: 600-750 mg/m2 PO Bid，continuous, for 1 year
arm group label: A
arm group label: B
arm group label: C
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Qiang Liu, MD
role: Principal Investigator
affiliation: Sunyat-sen Memorial Hospital
last name: Shunying Li, MD
phone: +86-15915939702
email: lishunying@foxmail.com
last name: Yudong Li, MD
phone: 020-34071156
email: 910870698@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
investigator full name: Liu Qiang
investigator title: Doctor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Capecitabine
mesh term: Tislelizumab