<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/NCT04499118</url>
  </required_header>
  <id_info>
    <org_study_id>BCHRD201</org_study_id>
    <nct_id>NCT04499118</nct_id>
  </id_info>
  <brief_title>AT Versus TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer</brief_title>
  <official_title>A Randomized Phase 2 Trial to Assess the Efficacy of AT in Comparison to TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer : Evaluating the Homologous Recombination Deficiency(HRD) Biomarker</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sichuan Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sichuan Provincial People's Hospital</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 is a prospective, randomized and open-label phase II study, evaluating the efficacy and&#xD;
      safety of AT vs TP regimen as neoadjuvant treatment for early HER2-negative breast cancer.&#xD;
      Participants will undergo/receive HRD testing after enrollment. HRD-positive patients will be&#xD;
      randomly assigned in a ratio of 1:1 to receive AT（Doxorubicin or Epirubicin+docetaxel）or&#xD;
      TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen respectively, followed by surgery.&#xD;
      HRD-negative patients will be assigned to receive TP（Albumin paclitaxel + Cisplatin or&#xD;
      Carboplatin）regimen if TNBC, or AT（Doxorubicin or Epirubicin+docetaxel）rigemen, followed by&#xD;
      surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study intends to adopt Simon's two-stage optimal design. In stage 1, 15 HRD-positive and&#xD;
      15 HRD-negative patients will be recruited to receive AT or TP regimen as neoadjuvant&#xD;
      therapy. If more than 5 patients in the HRD-positive group achieve pCR(pathological complete&#xD;
      response) , the trial expands to stage 2, otherwise the trial terminates. In stage 2, another&#xD;
      31 HRD- positive and 31 HRD-negative patients will be enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">August 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>Complete pathological response of breast and lymph nodes (ypT0/is ypN0; defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla)</measure>
    <time_frame>24 weeks</time_frame>
    <description>To compare the pathologic response to neoadjuvant AT regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation&#xD;
To compare the pathologic response to neoadjuvant TP regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation&#xD;
To compare the pathologic response to neoadjuvant AT vs TP regimen in HER2- breast cancer with HR-deficiency, defined as a high HRD score or a BRCA mutation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Imaging response</measure>
    <time_frame>24 weeks</time_frame>
    <description>To determine the response rates of the breast tumor and axillary nodes based on imaging tests. (sonography, mammography, or MRI) after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual cancer burden in patients with HRD</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>RCB in the breast tissue and the lymph node tissue will be performed after the completion of neoadjuvant systemic therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>response by pCR in HRD high versus tBRCA</measure>
    <time_frame>24 weeks</time_frame>
    <description>To assess the pCR rate in HRD high with vs without tBRCA mutation</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>HER2-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm a(HR+/HER2-,HRD-）</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive AT regimen for neoadjuvant therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm b(TNBC, HRD-)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive TP regimen for neoadjuvant therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm c(HER2-,HRD+)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive AT regimen for neoadjuvant therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm d(HER2-, HRD+)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive TP regimen for neoadjuvant therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AT regimen</intervention_name>
    <description>Doxorubin 60mg/㎡ d1 or Epirubicin 75mg/㎡ d1 Docetaxel 75mg/㎡ d1 1/21d</description>
    <arm_group_label>Arm a(HR+/HER2-,HRD-）</arm_group_label>
    <arm_group_label>Arm c(HER2-,HRD+)</arm_group_label>
    <other_name>Anthracycline/Paclitaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TP regimen</intervention_name>
    <description>Albumin paclitaxel 125mg/㎡ d1, 8 Cisplatin 75mg/㎡ d1-3 1/21d✖6 or carboplatin AUC6 d1 1/21d✖6</description>
    <arm_group_label>Arm b(TNBC, HRD-)</arm_group_label>
    <arm_group_label>Arm d(HER2-, HRD+)</arm_group_label>
    <other_name>Paclitaxel/Platinum</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent for all study specific procedures according to local&#xD;
             regulatory requirements prior to beginning specific protocol procedures.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Male or female patients&#xD;
&#xD;
          -  ECOG performance status ≤1&#xD;
&#xD;
          -  Histologically confirmed invasive breast cancer by core needle or incisional biopsy&#xD;
             (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical&#xD;
             exam or radiologic studies. In case of bilateral cancer, the investigator has to&#xD;
             decide prospectively which side will be evaluated for the primary endpoint.&#xD;
&#xD;
          -  Centrally confirmed negative HER2-status. Centrally confirmed estrogen and&#xD;
             progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is&#xD;
             defined as ≥1% stained cells and HER2-positive is defined as IHC 3+ or in-situ&#xD;
             hybridisation (ISH) ratio ≥2.0.&#xD;
&#xD;
          -  Provide Formalin-fixed, paraffin-embedded (FFPE) breast tissue to take Homologous&#xD;
             Recombinant Deficiency test.&#xD;
&#xD;
          -  Tumor lesion in the breast with a palpable size of &gt; 2 cm or a sonographical size of&#xD;
             &gt;1 cm in maximum diameter. If the tumor is not detectable with sonography mammography&#xD;
             assessment can be considered. The lesion has to be measurable in two dimensions,&#xD;
             preferably by sonography. In case of inflammatory disease, the extent of inflammation&#xD;
             can be used as measurable lesion.&#xD;
&#xD;
          -  Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or&#xD;
             shortening fraction) within 3 months prior to randomization. Results must be above the&#xD;
             normal limit of the institution.&#xD;
&#xD;
          -  Laboratory requirements:&#xD;
&#xD;
             i. Hematology b) Absolute neutrophil count (ANC) ≥2.0 x 109 / L and c) Platelets ≥100&#xD;
             x 109 / L and d) Hemoglobin ≥10 g/dL (≥ 6.2 mmol/L) Hepatic function e) Total&#xD;
             bilirubin ≥1.5x UNL and f) ASAT (SGOT) and ALAT (SGPT) ≥1.5x UNL and g) Alkaline&#xD;
             phosphatase ≥2.5x UNL.&#xD;
&#xD;
          -  Negative pregnancy test (urine or serum) within 14 days prior to randomization for all&#xD;
             women of childbearing potential.&#xD;
&#xD;
          -  Patients with a prior history of contra-lateral breast cancer are eligible if they&#xD;
             have no evidence of recurrence of their initial primary breast cancer within the last&#xD;
             5 years.&#xD;
&#xD;
          -  Individuals with a history of other malignancies are eligible if they have been&#xD;
             disease-free for at least 5 years and are deemed by the investigator to be at low risk&#xD;
             for recurrence of that malignancy and did not receive prior chemotherapy. Individuals&#xD;
             with the following cancers are eligible if diagnosed and treated within the past 5&#xD;
             years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.&#xD;
&#xD;
          -  Patients must be available and compliant for central diagnostics, treatment and&#xD;
             follow-up.&#xD;
&#xD;
          -  Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to&#xD;
             biopsy procedures patients must be able to be off medications that could increase the&#xD;
             risk of bleeding&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior chemotherapy for any malignancy within 3 years.&#xD;
&#xD;
          -  Any prior treatment for the current breast cancer, including chemotherapy, hormonal&#xD;
             therapy, radiation or experimental therapy.&#xD;
&#xD;
          -  Ongoing use of any other investigational or study agents.&#xD;
&#xD;
          -  Previous malignant disease without being disease-free for less than 5 years (except&#xD;
             CIS of the cervix and non-melanomatous skin cancer).&#xD;
&#xD;
          -  Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin&#xD;
             dose modification (i.e., Cre &gt; 1.5 mg/dl or GFR &lt; 60 cc/min).&#xD;
&#xD;
          -  Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based&#xD;
             chemotherapy).&#xD;
&#xD;
          -  Evidence of metastasis before randomization&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)&#xD;
             related diseases, active or symptomatic viral hepatitis or chronic liver disease&#xD;
&#xD;
          -  Known history of heart disease, for example: myocardial infarction or symptomatic&#xD;
             cardiac ischemia within 24 weeks before screening; congestive heart failure;&#xD;
             randomized history of clinically significant ventricular arrhythmias within the&#xD;
             previous year; Mobitz II level 2 Or a history of tertiary heart block, hypertension is&#xD;
             uncontrolled&#xD;
&#xD;
          -  History of significant neurological or psychiatric disorders including psychotic&#xD;
             disorders, dementia or seizures that would prohibit the understanding and giving of&#xD;
             informed consent.&#xD;
&#xD;
          -  Have undergone major surgery within 14 days before entering the study&#xD;
&#xD;
          -  Any other reason the investigator considers inappropriate to participate in this&#xD;
             clinical trial&#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>Prof. Luojing</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sichuan Provincial People's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Prof. Luojing</last_name>
    <phone>86-18981838521</phone>
    <email>luckyluojingyu@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of breast surgery, Sichuan Provincial People's Hospital</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610031</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. doi: 10.1038/s41591-018-0009-7. Epub 2018 Apr 30.</citation>
    <PMID>29713086</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sichuan Provincial People's Hospital</investigator_affiliation>
    <investigator_full_name>Luojing</investigator_full_name>
    <investigator_title>Prof.</investigator_title>
  </responsible_party>
  <keyword>Breast neoplasms</keyword>
  <keyword>HER2-</keyword>
  <keyword>Homologous Recombination Deficiency</keyword>
  <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>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04499118
org study id: BCHRD201
nct id: NCT04499118
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a prospective, randomized and open-label phase II study, evaluating the efficacy and
      safety of AT vs TP regimen as neoadjuvant treatment for early HER2-negative breast cancer.
      Participants will undergo/receive HRD testing after enrollment. HRD-positive patients will be
      randomly assigned in a ratio of 1:1 to receive AT（Doxorubicin or Epirubicin+docetaxel）or
      TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen respectively, followed by surgery.
      HRD-negative patients will be assigned to receive TP（Albumin paclitaxel + Cisplatin or
      Carboplatin）regimen if TNBC, or AT（Doxorubicin or Epirubicin+docetaxel）rigemen, followed by
      surgery.
This study intends to adopt Simon's two-stage optimal design. In stage 1, 15 HRD-positive and
      15 HRD-negative patients will be recruited to receive AT or TP regimen as neoadjuvant
      therapy. If more than 5 patients in the HRD-positive group achieve pCR(pathological complete
      response) , the trial expands to stage 2, otherwise the trial terminates. In stage 2, another
      31 HRD- positive and 31 HRD-negative patients will be enrolled.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete pathological response of breast and lymph nodes (ypT0/is ypN0; defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla)
time frame: 24 weeks
description: To compare the pathologic response to neoadjuvant AT regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation
To compare the pathologic response to neoadjuvant TP regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation
To compare the pathologic response to neoadjuvant AT vs TP regimen in HER2- breast cancer with HR-deficiency, defined as a high HRD score or a BRCA mutation
measure: Imaging response
time frame: 24 weeks
description: To determine the response rates of the breast tumor and axillary nodes based on imaging tests. (sonography, mammography, or MRI) after treatment.
measure: Residual cancer burden in patients with HRD
time frame: up to 24 weeks
description: RCB in the breast tissue and the lymph node tissue will be performed after the completion of neoadjuvant systemic therapy.
measure: response by pCR in HRD high versus tBRCA
time frame: 24 weeks
description: To assess the pCR rate in HRD high with vs without tBRCA mutation
arm group label: Arm a(HR+/HER2-,HRD-）
arm group type: Experimental
description: Participants receive AT regimen for neoadjuvant therapy
arm group label: Arm b(TNBC, HRD-)
arm group type: Experimental
description: Participants receive TP regimen for neoadjuvant therapy
arm group label: Arm c(HER2-,HRD+)
arm group type: Experimental
description: Participants receive AT regimen for neoadjuvant therapy
arm group label: Arm d(HER2-, HRD+)
arm group type: Experimental
description: Participants receive TP regimen for neoadjuvant therapy
intervention type: Drug
intervention name: AT regimen
description: Doxorubin 60mg/㎡ d1 or Epirubicin 75mg/㎡ d1 Docetaxel 75mg/㎡ d1 1/21d
arm group label: Arm a(HR+/HER2-,HRD-）
arm group label: Arm c(HER2-,HRD+)
other name: Anthracycline/Paclitaxel
intervention type: Drug
intervention name: TP regimen
description: Albumin paclitaxel 125mg/㎡ d1, 8 Cisplatin 75mg/㎡ d1-3 1/21d✖6 or carboplatin AUC6 d1 1/21d✖6
arm group label: Arm b(TNBC, HRD-)
arm group label: Arm d(HER2-, HRD+)
other name: Paclitaxel/Platinum
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Prof. Luojing
role: Principal Investigator
affiliation: Sichuan Provincial People's Hospital
last name: Prof. Luojing
phone: 86-18981838521
email: luckyluojingyu@163.com
facility: 
country: China
citation: Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. doi: 10.1038/s41591-018-0009-7. Epub 2018 Apr 30.
PMID: 29713086
responsible party type: Principal Investigator
investigator affiliation: Sichuan Provincial People's Hospital
investigator full name: Luojing
investigator title: Prof.
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
sharing ipd: No