<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/NCT03756298</url>
  </required_header>
  <id_info>
    <org_study_id>ATOX-2018</org_study_id>
    <nct_id>NCT03756298</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Atezolizumab Plus Capecitabine Adjuvant Therapy for Triple Receptor-Negative Breast Cancer</brief_title>
  <official_title>Randomized, Phase II Trial to Evaluate the Efficacy and Safety of Atezolizumab Plus Capecitabine Adjuvant Therapy Compared to Capecitabine Monotherapy for TNBC With Residual Invasive Cancer After Neoadjuvant Chemotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Center, Korea</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Center, Korea</source>
  <oversight_info>
    <has_dmc>No</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>
      This study will enroll patients who received neoadjuvant therapy for TNBC prior to surgery&#xD;
      and did not get pCR. Given the relatively poor prognosis for these patients, this population&#xD;
      is considered novel therapeutic as adjuvant treatment. Currently, capecitabine monotherapy&#xD;
      could be beneficial to this group of patients according to CREATE-X trial results. The&#xD;
      investigators are addressing the effect of anti-PD-L1, atezolizumab combined with&#xD;
      capecitabine in patients with TNBC who did not get pCR after neoadjuvant chemotherapy&#xD;
      compared to capecitabine monotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>5-yr invasive disease-free survival (IDFS) rate</measure>
    <time_frame>3 years after last patient enrollment</time_frame>
    <description>• To compare 5-yr invasive disease-free survival (IDFS) rate of patients with triple-negative breast cancer (TNBC) who had either ≥ 1 cm residual invasive breast cancer and/or positive lymph nodes (&gt; ypN+) after neoadjuvant chemotherapy</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">284</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Atezolizumab + capecitabine combination arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Capecitabine alone arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab is 1,200 mg iv. administered every 3 weeks for 8 cycles with capecitabine (2,000mg/m2/day, day 1-14, every 3 weeks for 8 cycles)</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Arm A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>capecitabine monotherapy (2,500mg/m2/day, day 1-14, every 3 weeks for 8 cycles)</description>
    <arm_group_label>Combination</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <other_name>Arm B</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  - Male or female ≥ 19 years of age&#xD;
&#xD;
          -  Patients must have histologically confirmed estrogen receptor (ER)-, progesterone&#xD;
             receptor (PR)- and HER2-negative (triple-negative) with residual invasive breast&#xD;
             cancer, as defined by the 2010 and 2013 American Society of Clinical Oncology (ASCO)&#xD;
             College of American Pathologists (CAP) guidelines (Wolff AC, Hammond MEH), after&#xD;
             completion of neoadjuvant chemotherapy; residual disease must be ≥ 1 cm in greatest&#xD;
             dimension, and/or have macroscopically positive lymph nodes (ypN+) observed on&#xD;
             pathologic exam&#xD;
&#xD;
          -  Patients must not have metastatic disease (i.e., must be M0)&#xD;
&#xD;
          -  Patients must have a minimum of 20, available unstained slides from the residual&#xD;
             (post-neoadjuvant) invasive tumor in primary site or lymph node to be submitted to&#xD;
             determine PD-L1 expression and other biomarker analysis&#xD;
&#xD;
          -  Patients must have had neoadjuvant chemotherapy followed by surgery; the recommended&#xD;
             neoadjuvant treatment should include 16-24 weeks of a third generation chemotherapy&#xD;
             regimen as recommended by National Comprehensive Cancer Network (NCCN) guidelines for&#xD;
             triple negative breast cancer. Patients who cannot complete all planned treatment&#xD;
             cycles for any reason are considered high risk and therefore are eligible for the&#xD;
             study if they have residual disease&#xD;
&#xD;
          -  Patients must have completed their final breast surgery with clear resection margins&#xD;
             for invasive cancer and ductal carcinoma in situ (DCIS) within 90 days prior to&#xD;
             screening&#xD;
&#xD;
          -  Patients for whom radiation therapy (RT) to the affected breast or chest wall and&#xD;
             regional nodal areas is clinically indicated as per NCCN treatment guidelines, should&#xD;
             receive RT before study treatment; RT administered after registration is also allowed&#xD;
&#xD;
          -  Patients must have resolution of adverse event(s) of the most recent prior&#xD;
             chemotherapy and RT to grade 1 or less, except alopecia and ≤ grade 2 neuropathy which&#xD;
             are allowed&#xD;
&#xD;
          -  Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4&#xD;
             or similar drugs&#xD;
&#xD;
          -  Patients must not have had prior capecitabine therapy.&#xD;
&#xD;
          -  Patients must not have had a history of severe allergic, anaphylactic, or other&#xD;
             hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins,&#xD;
             known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster&#xD;
             ovary cells or any component of the atezolizumab formulation&#xD;
&#xD;
          -  Patients must have ECOG performance status &lt; 2&#xD;
&#xD;
          -  Patients must sign and give written informed consent for this protocol in accordance&#xD;
             with institutional guidelines&#xD;
&#xD;
          -  Patients should have adequate organ function within 21 days prior to the start of&#xD;
             study treatment (cycle 1, day1).&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500/uL; without granulocyte colony stimulating&#xD;
                  factor (G-CSF) support within 2 weeks prior to the first study treatment&#xD;
                  administration&#xD;
&#xD;
               -  Lymphocyte count ≥ 500/uL&#xD;
&#xD;
               -  Platelet count ≥ 100,000/uL (without transfusion within 2 weeks prior to the&#xD;
                  first study treatment administration)&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0g/dL&#xD;
&#xD;
               -  AST, ALT, and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN)&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5x ULN, patients with known Gilbert disease who have serum&#xD;
                  bilirubin ≤ 3.0x ULN may be enrolled.&#xD;
&#xD;
               -  INR and aPTT ≤ 1.5x ULN, This applies only to patients who are not receiving&#xD;
                  therapeutic anticoagulation; patients receiving therapeutic anticoagulation&#xD;
                  should be on a stable dose.&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 30mL/min&#xD;
&#xD;
          -  Women of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 28 day prior to registration; women/men of reproductive potential must have&#xD;
             agreed to use an effective contraceptive method for the course of the study through&#xD;
             150 days after the last dose of study medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - Patients with evident metastatic lesions at the time of diagnosis&#xD;
&#xD;
          -  Patients who underwent incomplete surgery for breast cancer&#xD;
&#xD;
          -  Malignancies other than TNBC within 5 years prior to randomization, with the exception&#xD;
             of those with well-differentiated thyroid cancer, carcinoma in situ of the cervix or&#xD;
             basal or squamous cell skin cancer.&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Evidence of significant uncontrolled concomitant disease that could affect compliance&#xD;
             with the protocol including significant liver disease, uncontrolled major seizure&#xD;
             disorder, or uncontrolled psychological disorder.&#xD;
&#xD;
          -  Significant cardiovascular disease, such as New York Hear Association (NYHA) cardiac&#xD;
             disease (class II or greater), myocardial infarction within 3 months prior to&#xD;
             randomization, unstable arrhythmia, or unstable angina.&#xD;
&#xD;
             : Patients with a known left ventricular ejection fraction (LVEF) &lt;50% will be&#xD;
             excluded.&#xD;
&#xD;
          -  Patients who have a history of interstitial pneumonitis that required steroids or&#xD;
             evidence of active pneumonitis.&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and&#xD;
             unexpected reactions to fluoropyrimidine therapy in patients selected to receive&#xD;
             capecitabine&#xD;
&#xD;
          -  Hypersensitivity to any component of capecitabine drug formulation in patients&#xD;
             selected to receive capecitabine.&#xD;
&#xD;
          -  Patients who have an active infection requiring systemic therapy&#xD;
&#xD;
          -  Patients who have active autoimmune disease that has required systemic treatment in&#xD;
             past 2 years (i.e., with use of disease modifying agents, corticosteroids or&#xD;
             immunosuppressive drugs); patients who are on a stable dose of replacement therapy&#xD;
             (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for&#xD;
             adrenal or pituitary insufficiency, etc.) are eligible for this study&#xD;
&#xD;
          -  Patients who have known active hepatitis B virus (HBV) or hepatitis C virus (HCV)&#xD;
             infection prior to registration; patients who have completed curative therapy for HCV&#xD;
             are eligible; patients with known human immunodeficiency virus (HIV) infection are not&#xD;
             eligible&#xD;
&#xD;
          -  Patients who have received live vaccines within 30 days prior to registration;&#xD;
             examples of live vaccines include, but are not limited to, the following: measles,&#xD;
             mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin&#xD;
             (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are&#xD;
             generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
             vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed&#xD;
&#xD;
          -  Known hypersensitivity to any of excipients of study drugs.&#xD;
&#xD;
          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies or fusion proteins.&#xD;
&#xD;
          -  Prior allogenic stem cell or solid organ transplantation&#xD;
&#xD;
          -  Treatment with systemic immunostimulatory agents (including but not limited to&#xD;
             interferons or IL-2) within 4 weeks or five half-lives of the drug( whichever is&#xD;
             shorter) prior to randomization&#xD;
&#xD;
          -  Treatment with systemic corticosteroids or other systemic immunosuppressive&#xD;
             medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,&#xD;
             azathioprine, methotrexate, thalidomide, and anti-TNF agents etc.) within 2 weeks&#xD;
             prior to randomization&#xD;
&#xD;
               -  patients who have received acute, low-dose, systemic immunosuppressant&#xD;
                  medications may be enrolled in the study&#xD;
&#xD;
               -  The use of inhaled corticosteroids for chronic obstructive pulmonary disease, and&#xD;
                  low-dose supplemental corticosteroids for adrenocortical insufficiency are&#xD;
                  allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Korea University, Guro hospital</name>
      <address>
        <city>Seoul</city>
        <zip>08308</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>In Hae Park, doctor</last_name>
      <phone>+82-2-2626-3310</phone>
      <email>parkinhae@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Junga-A Park, CRC</last_name>
      <phone>+82-31-920-0441</phone>
      <email>p1209s@ncc.re.kr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>March 10, 2021</last_update_submitted>
  <last_update_submitted_qc>March 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Center, Korea</investigator_affiliation>
    <investigator_full_name>In Hae Park</investigator_full_name>
    <investigator_title>Senior Scientist</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>Atezolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03756298
org study id: ATOX-2018
nct id: NCT03756298
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will enroll patients who received neoadjuvant therapy for TNBC prior to surgery
      and did not get pCR. Given the relatively poor prognosis for these patients, this population
      is considered novel therapeutic as adjuvant treatment. Currently, capecitabine monotherapy
      could be beneficial to this group of patients according to CREATE-X trial results. The
      investigators are addressing the effect of anti-PD-L1, atezolizumab combined with
      capecitabine in patients with TNBC who did not get pCR after neoadjuvant chemotherapy
      compared to capecitabine monotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: 5-yr invasive disease-free survival (IDFS) rate
time frame: 3 years after last patient enrollment
description: • To compare 5-yr invasive disease-free survival (IDFS) rate of patients with triple-negative breast cancer (TNBC) who had either ≥ 1 cm residual invasive breast cancer and/or positive lymph nodes (> ypN+) after neoadjuvant chemotherapy
arm group label: Combination
arm group type: Experimental
description: Atezolizumab + capecitabine combination arm
arm group label: Control
arm group type: Active Comparator
description: Capecitabine alone arm
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab is 1,200 mg iv. administered every 3 weeks for 8 cycles with capecitabine (2,000mg/m2/day, day 1-14, every 3 weeks for 8 cycles)
arm group label: Control
other name: Arm A
intervention type: Drug
intervention name: Capecitabine
description: capecitabine monotherapy (2,500mg/m2/day, day 1-14, every 3 weeks for 8 cycles)
arm group label: Combination
arm group label: Control
other name: Arm B
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: National Cancer Center, Korea
investigator full name: In Hae Park
investigator title: Senior Scientist
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Capecitabine
mesh term: Atezolizumab
sharing ipd: Undecided