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/NCT05973864</url>
    </required_header>
    <id_info>
      <org_study_id>UC-BCG-2211</org_study_id>
      <secondary_id>2023-505291-30-00</secondary_id>
      <nct_id>NCT05973864</nct_id>
    </id_info>
    <brief_title>Capecitabine Plus Pembrolizumab in Patients With Triple Negative Breast Cancer After Chemo-immunotherapy and Surgery</brief_title>
    <acronym>CAPPA</acronym>
    <official_title>A Phase III, Randomized, Open-label Study to Evaluate Capecitabine Plus Pembrolizumab vs Pembrolizumab Alone as Post-operative Therapy for Triple Negative Breast Cancer With Residual Disease After Neoadjuvant Chemo-immunotherapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>UNICANCER</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>UNICANCER</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>
        The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and&#xD;
        capecitabine compare to pembrolizumab alone, on the invasive disease-free survival, in&#xD;
        participants who have triple negative breast cancer (TNBC) with residual disease after&#xD;
        neoadjuvant chemotherapy associated with pembrolizumab.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2024</start_date>
    <completion_date type="Anticipated">January 2029</completion_date>
    <primary_completion_date type="Anticipated">January 2026</primary_completion_date>
    <phase>Phase 3</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>Invasive Disease-free survival (iDFS)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>Invasive disease free survival (iDFS) defined as time from randomization to the first of the following events: local, regional or distant recurrence, or second primary cancer (including contralateral) or death due to any cause.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>From randomization to death of any cause, up to 5 years.</time_frame>
      <description>The overall survival is the length of time from randomization that patients enrolled in the study are still alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distant disease-free survival (DDFS)</measure>
      <time_frame>Throughout study completion, up to 5 years.</time_frame>
      <description>Distant disease-free survival (DDFS) is defined as the time from the date of randomization to the date of distant relapse or death due to any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Acute and late toxicity during the study</measure>
      <time_frame>Throughout study completion, up to 5 years.</time_frame>
      <description>The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = &quot;mild&quot;, 2 = &quot;moderate&quot;, 3 = &quot;severe&quot;, 4 = &quot;life-threatening&quot;, and 5 = &quot;death&quot;) determined by the investigator, will make it possible to assess the severity of the disorders.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">418</enrollment>
    <condition>Triple Negative Breast Neoplasms</condition>
    <arm_group>
      <arm_group_label>Arm A : Pembrolizumab and capecitabine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pembrolizumab will be administered at a fixed dose of 200 mg every 3 weeks (Q3W), with a total of 9 cycles at adjuvant phase of the treatment;&#xD;
  Capecitabine will be administrated at a dose of 1250 mg/m² twice a day (BID) (14 days on / 7 days off) for a total of 8 cycles, with a dose reduction at 825 mg/m² BID during radiotherapy if indicated&#xD;
  Local radiotherapy will be performed as per standard practice if indicated.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm B : Pembrolizumab alone</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Pembrolizumab will be administered at a fixed dose of 200 mg Q3W, with a total of 9 cycles at adjuvant phase of the treatment;&#xD;
  Local radiotherapy will be performed as per standard practice if indicated.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab injection</intervention_name>
      <description>On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion</description>
      <arm_group_label>Arm A : Pembrolizumab and capecitabine</arm_group_label>
      <arm_group_label>Arm B : Pembrolizumab alone</arm_group_label>
      <other_name>KEYTRUDA®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine tablets</intervention_name>
      <description>1250 mg/m² BID, on days 1-14 of each 21-day cycle; 8 cycles Dose reduction at 825 mg/m² BID during radiotherapy if indicated</description>
      <arm_group_label>Arm A : Pembrolizumab and capecitabine</arm_group_label>
      <other_name>Xeloda</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Local radiotherapy</intervention_name>
      <description>Local radiotherapy will be performed as per standard practice if indicated.</description>
      <arm_group_label>Arm A : Pembrolizumab and capecitabine</arm_group_label>
      <arm_group_label>Arm B : Pembrolizumab alone</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient must have signed a written informed consent prior to any trial specific&#xD;
               procedures. When the patient is physically unable to give their written consent, a&#xD;
               trusted person of their choice, independent from the investigator or the sponsor, can&#xD;
               confirm in writing the patient's consent;&#xD;
  &#xD;
            2. Subject ≥ 18 years of age on day of signing informed consent form;&#xD;
  &#xD;
            3. Histologically proven TNBC defined as follows:&#xD;
  &#xD;
                 1. Human epidermal growth factor receptor 2 (HER2) negativity (American Society of&#xD;
                    Clinical Oncology and the College of American Pathologists (ASCO/CAP) criteria),&#xD;
  &#xD;
                 2. AND less than 10% of cells stained by immunohistochemistry for estrogen receptor&#xD;
                    and Progesterone receptor;&#xD;
  &#xD;
            4. TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum&#xD;
               of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and&#xD;
               pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin).&#xD;
               Other drugs may be acceptable following discussion with the sponsor (with the&#xD;
               exclusion of capecitabine);&#xD;
  &#xD;
            5. Complete resection of the breast tumor(s) (and of any invaded lymph node);&#xD;
  &#xD;
            6. No complete pathological response, defined as residual cancer burden (RCB) Class I,&#xD;
               II, or III (per local assessment); Note: the final recruited population will contain&#xD;
               no more than 25% of patients with RCB I response.&#xD;
  &#xD;
            7. Available representative formalin-fixed paraffin-embedded tumor block from surgery&#xD;
               specimen with its histological report;&#xD;
  &#xD;
            8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;&#xD;
  &#xD;
            9. Adequate organ and bone marrow function. All screening lab tests should be performed&#xD;
               within 28 days before randomization;&#xD;
  &#xD;
           10. Resolution to at least grade 1 of all acute toxicities from previous therapies&#xD;
               including immune related toxicity due to pembrolizumab, except alopecia,&#xD;
               immune-related endocrinopathies receiving hormone replacement, and ≤ grade 2 of&#xD;
               neuropathy toxicity which are allowed;&#xD;
  &#xD;
           11. Minimal/maximal period for prior treatments (i.e. minimal delay from last dose of&#xD;
               prior treatment to cycle 1 dose 1 (C1D1)): breast surgery (the wound must have healed&#xD;
               prior to C1D1) ≥2 weeks (maximum 10 weeks); last pembrolizumab injection ≥3 weeks;&#xD;
  &#xD;
           12. Women of child-bearing potential must have a negative serum pregnancy test within 7&#xD;
               days before C1D1;&#xD;
  &#xD;
           13. Women of child-bearing potential and male patients must agree to use 1 effective form&#xD;
               of contraception from the time of the negative pregnancy test up to 6 months after the&#xD;
               last dose of study drugs;&#xD;
  &#xD;
           14. Patient should be able and willing to comply with study visits and procedures as per&#xD;
               protocol;&#xD;
  &#xD;
           15. Patients must be covered by the French medical insurance.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Radiological or clinical evidence of metastatic disease documented by imaging or&#xD;
               clinical examination performed during screening period;&#xD;
  &#xD;
            2. Has received capecitabine or other immune-checkpoint inhibitors (ICI) than&#xD;
               pembrolizumab in the neoadjuvant chemotherapy (NAC) regimen;&#xD;
  &#xD;
            3. Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell&#xD;
               carcinoma of the skin, or in situ cervical cancer or previously treated malignancy&#xD;
               with no evidence of disease for ≥ 2 years;&#xD;
  &#xD;
            4. Presents a contraindication to continue pembrolizumab treatment as per respective&#xD;
               summary of product characteristics (SmPC) including known hypersensitivity;&#xD;
  &#xD;
            5. Previous immune-related adverse event of any grade due to pembrolizumab that led to&#xD;
               permanent discontinuation of pembrolizumab;&#xD;
  &#xD;
            6. Presents a contraindication to capecitabine treatment as per SmPC;&#xD;
  &#xD;
            7. Complete Dihydropyrimidine Dehydrogenase (DPD) deficiency;&#xD;
  &#xD;
            8. Require the use of one of the following forbidden treatments during the study&#xD;
               treatment period:&#xD;
  &#xD;
                 -  Any investigational anticancer therapy other than the protocol specified&#xD;
                    treatment,&#xD;
  &#xD;
                 -  Any concurrent chemotherapy, immunotherapy, biologic for cancer treatment, other&#xD;
                    than the ones stated in the protocol;&#xD;
  &#xD;
            9. Pregnant women or women who are breast-feeding;&#xD;
  &#xD;
           10. Patients unwilling or unable to comply with the medical follow-up required by the&#xD;
               trial because of geographic, familial, social, or psychological reasons;&#xD;
  &#xD;
           11. Persons deprived of their liberty or under protective custody or guardianship;&#xD;
  &#xD;
           12. Participation in another therapeutic trial within the 30 days prior to randomization.&#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_official>
      <last_name>Delphine LOIRAT, MD PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institut Curie Paris</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Telma ROQUE, PhD</last_name>
      <phone>+33 (0) 1 80 50 12 92</phone>
      <email>cappa@unicancer.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jérôme LEMONNIER, PhD</last_name>
      <phone>+33 (0) 1 71 93 67 02</phone>
      <email>j-lemonnier@unicancer.fr</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
      <mesh_term>Capecitabine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.</ipd_description>
    </patient_data>
    <!-- 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/NCT05973864
  org study id: UC-BCG-2211
  secondary id: 2023-505291-30-00
  nct id: NCT05973864
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and
        capecitabine compare to pembrolizumab alone, on the invasive disease-free survival, in
        participants who have triple negative breast cancer (TNBC) with residual disease after
        neoadjuvant chemotherapy associated with pembrolizumab.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Invasive Disease-free survival (iDFS)
  time frame: Up to 5 years
  description: Invasive disease free survival (iDFS) defined as time from randomization to the first of the following events: local, regional or distant recurrence, or second primary cancer (including contralateral) or death due to any cause.
  measure: Overall survival (OS)
  time frame: From randomization to death of any cause, up to 5 years.
  description: The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
  measure: Distant disease-free survival (DDFS)
  time frame: Throughout study completion, up to 5 years.
  description: Distant disease-free survival (DDFS) is defined as the time from the date of randomization to the date of distant relapse or death due to any cause, whichever occurs first.
  measure: Acute and late toxicity during the study
  time frame: Throughout study completion, up to 5 years.
  description: The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
  arm group label: Arm A : Pembrolizumab and capecitabine
  arm group type: Experimental
  description: Pembrolizumab will be administered at a fixed dose of 200 mg every 3 weeks (Q3W), with a total of 9 cycles at adjuvant phase of the treatment;
  Capecitabine will be administrated at a dose of 1250 mg/m² twice a day (BID) (14 days on / 7 days off) for a total of 8 cycles, with a dose reduction at 825 mg/m² BID during radiotherapy if indicated
  Local radiotherapy will be performed as per standard practice if indicated.
  arm group label: Arm B : Pembrolizumab alone
  arm group type: Active Comparator
  description: Pembrolizumab will be administered at a fixed dose of 200 mg Q3W, with a total of 9 cycles at adjuvant phase of the treatment;
  Local radiotherapy will be performed as per standard practice if indicated.
  intervention type: Drug
  intervention name: Pembrolizumab injection
  description: On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion
  arm group label: Arm A : Pembrolizumab and capecitabine
  arm group label: Arm B : Pembrolizumab alone
  other name: KEYTRUDA®
  intervention type: Drug
  intervention name: Capecitabine tablets
  description: 1250 mg/m² BID, on days 1-14 of each 21-day cycle; 8 cycles Dose reduction at 825 mg/m² BID during radiotherapy if indicated
  arm group label: Arm A : Pembrolizumab and capecitabine
  other name: Xeloda
  intervention type: Radiation
  intervention name: Local radiotherapy
  description: Local radiotherapy will be performed as per standard practice if indicated.
  arm group label: Arm A : Pembrolizumab and capecitabine
  arm group label: Arm B : Pembrolizumab alone
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Delphine LOIRAT, MD PhD
  role: Principal Investigator
  affiliation: Institut Curie Paris
  last name: Telma ROQUE, PhD
  phone: +33 (0) 1 80 50 12 92
  email: cappa@unicancer.fr
  last name: Jérôme LEMONNIER, PhD
  phone: +33 (0) 1 71 93 67 02
  email: j-lemonnier@unicancer.fr
  responsible party type: Sponsor
  mesh term: Triple Negative Breast Neoplasms
  mesh term: Breast Neoplasms
  mesh term: Pembrolizumab
  mesh term: Capecitabine
  sharing ipd: No
  ipd description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.