<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/NCT04419181</url>
  </required_header>
  <id_info>
    <org_study_id>UBRS20013</org_study_id>
    <nct_id>NCT04419181</nct_id>
  </id_info>
  <brief_title>Feasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer</brief_title>
  <official_title>A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this research study is to find out if de-escalation of chemotherapy&#xD;
      before surgery followed by a selective escalation of adjuvant targeted therapies are&#xD;
      efficacious and tolerable in early-stage HER2 positive breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Assess the feasibility of four cycles of neoadjuvant Docetaxel Carboplatin Trastuzumab and&#xD;
      Pertuzumab (TCHP) in women with early-stage (local/locally advanced) HER2+ breast cancer with&#xD;
      a selective escalation of targeted HER2 directed therapy in the high risk group in the&#xD;
      adjuvant setting. Participants with any residual disease after four cycles of TCHP will&#xD;
      receive Trastuzumab Emtansine (TDM1) plus Pertuzumab while those with complete pathological&#xD;
      response will receive Trastuzumab in the adjuvant settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">June 1, 2023</start_date>
  <completion_date type="Anticipated">June 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be assigned to an arm of the trial based on their outcomes after surgery.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>One Year Invasive Disease-Free Survival</measure>
    <time_frame>One year from the breast cancer surgery</time_frame>
    <description>The study will be considered feasible if the researchers observe the invasive disease free survival (IDFS) estimate at one year to be 90% or more among those who achieved a pCR, or if the researchers observe the IDFS estimate at one year to be 85% or more among those who had residual disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pathologic Complete Response rate</measure>
    <time_frame>12 weeks from start of treatment</time_frame>
    <description>Assess the pCR rate after four cycles (12 weeks) of TCHP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity of chemo and HER2 therapies</measure>
    <time_frame>One year from the start of treatment</time_frame>
    <description>Evaluate toxicity associated with neoadjuvant and adjuvant chemo and/or HER2 directed therapies. Percentage of grade 1 to grade 5 toxicities will be assessed during the neo-adjuvant TCHP therapy for all participants. Percentage of grade 1 to grade 5 toxicities will be assessed with adjuvant trastuzumab therapy for the cohort with pathological complete response, and with optional adjuvant TCHP therapy and adjuvant TDM1 + pertuzumab therapy for the residual disease cohort. Toxicity data will be obtained based on the clinical assessment of the participants by the investigators and based on laboratory data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Two Year Invasive Disease-Free Survival</measure>
    <time_frame>Two years from the breast cancer surgery</time_frame>
    <description>Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>HER2-positive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Pathologic complete response (pCR)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive four cycles of TCHP [docetaxel (Taxotere®), carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who achieve pathologic complete response will receive infusions of trastuzumab every 3 weeks for a total of 12 cycles/infusions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Residual Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive four cycles of TCHP [docetaxel (Taxotere®, carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who have residual disease may be offered two more cycles of TCHP in the adjuvant settings (optional) per treating oncologist's discretion and then will receive infusion of Trastuzumab Emtansine (TDM1) plus pertuzumab every three weeks for a total of 12 cycles/infusions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Dose: 75 mg/m2 q3w</description>
    <arm_group_label>Pathologic complete response (pCR)</arm_group_label>
    <arm_group_label>Residual Disease</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Dose: area under the concentration-time curve [AUC] 6 q3w</description>
    <arm_group_label>Pathologic complete response (pCR)</arm_group_label>
    <arm_group_label>Residual Disease</arm_group_label>
    <other_name>Paraplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w</description>
    <arm_group_label>Pathologic complete response (pCR)</arm_group_label>
    <arm_group_label>Residual Disease</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pertuzumab</intervention_name>
    <description>Dose: 840-mg loading dose, 420-mg maintenance dose q3w</description>
    <arm_group_label>Pathologic complete response (pCR)</arm_group_label>
    <arm_group_label>Residual Disease</arm_group_label>
    <other_name>Perjeta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab emtansine</intervention_name>
    <description>Dose: 3.6mg/kg q3w</description>
    <arm_group_label>Residual Disease</arm_group_label>
    <other_name>TDM1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women ≥18 years of age&#xD;
&#xD;
          -  Biopsy proven HER2+ early breast cancer&#xD;
&#xD;
          -  ECOG performance status 0-1&#xD;
&#xD;
          -  Should be a candidate for neoadjuvant chemotherapy using standard guidelines of tumor&#xD;
             size of 2cm or more and /or axillary lymph node-positive disease.&#xD;
&#xD;
          -  Adequate cardiac, bone marrow, kidney, and liver functions per treating physician's&#xD;
             discretion.&#xD;
&#xD;
          -  Women of childbearing potential who are sexually active must agree to use highly&#xD;
             effective methods of contraception during treatment and for three weeks after the last&#xD;
             dose of chemotherapy or anti-HER2 therapy. The women currently using hormonal&#xD;
             contraceptives must agree to change to an alternative highly effective method of&#xD;
             contraception&#xD;
&#xD;
          -  Willingness and ability to comply with study and follow-up procedures and give written&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any evidence of stage IV breast cancer&#xD;
&#xD;
          -  Participant deemed unsuitable for clinical trial enrolment by treating physician based&#xD;
             on the participants' compliance, location and commute requirements, or tolerance of&#xD;
             therapies involved&#xD;
&#xD;
          -  Any invasive malignancy within the last two years of study enrollment except for&#xD;
             adequately treated basal cell carcinoma, squamous cell carcinoma, or non-melanoma skin&#xD;
             cancer.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ajay Dhakal, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ajay Dhakal, MBBS</last_name>
    <phone>585-275-5863</phone>
    <email>Ajay_Dhakal@urmc.rochester.edu</email>
  </overall_contact>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>August 31, 2022</last_update_submitted>
  <last_update_submitted_qc>August 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Ajay Dhakal</investigator_full_name>
    <investigator_title>Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)</investigator_title>
  </responsible_party>
  <keyword>HER2-positive Breast Cancer</keyword>
  <keyword>De-escalation</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>Carboplatin</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Ado-Trastuzumab Emtansine</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/NCT04419181
org study id: UBRS20013
nct id: NCT04419181
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The main purpose of this research study is to find out if de-escalation of chemotherapy
      before surgery followed by a selective escalation of adjuvant targeted therapies are
      efficacious and tolerable in early-stage HER2 positive breast cancer.
Assess the feasibility of four cycles of neoadjuvant Docetaxel Carboplatin Trastuzumab and
      Pertuzumab (TCHP) in women with early-stage (local/locally advanced) HER2+ breast cancer with
      a selective escalation of targeted HER2 directed therapy in the high risk group in the
      adjuvant setting. Participants with any residual disease after four cycles of TCHP will
      receive Trastuzumab Emtansine (TDM1) plus Pertuzumab while those with complete pathological
      response will receive Trastuzumab in the adjuvant settings.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be assigned to an arm of the trial based on their outcomes after surgery.
primary purpose: Treatment
masking: None (Open Label)
measure: One Year Invasive Disease-Free Survival
time frame: One year from the breast cancer surgery
description: The study will be considered feasible if the researchers observe the invasive disease free survival (IDFS) estimate at one year to be 90% or more among those who achieved a pCR, or if the researchers observe the IDFS estimate at one year to be 85% or more among those who had residual disease.
measure: Pathologic Complete Response rate
time frame: 12 weeks from start of treatment
description: Assess the pCR rate after four cycles (12 weeks) of TCHP.
measure: Toxicity of chemo and HER2 therapies
time frame: One year from the start of treatment
description: Evaluate toxicity associated with neoadjuvant and adjuvant chemo and/or HER2 directed therapies. Percentage of grade 1 to grade 5 toxicities will be assessed during the neo-adjuvant TCHP therapy for all participants. Percentage of grade 1 to grade 5 toxicities will be assessed with adjuvant trastuzumab therapy for the cohort with pathological complete response, and with optional adjuvant TCHP therapy and adjuvant TDM1 + pertuzumab therapy for the residual disease cohort. Toxicity data will be obtained based on the clinical assessment of the participants by the investigators and based on laboratory data.
measure: Two Year Invasive Disease-Free Survival
time frame: Two years from the breast cancer surgery
description: Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease
arm group label: Pathologic complete response (pCR)
arm group type: Experimental
description: Participants will receive four cycles of TCHP [docetaxel (Taxotere®), carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who achieve pathologic complete response will receive infusions of trastuzumab every 3 weeks for a total of 12 cycles/infusions.
arm group label: Residual Disease
arm group type: Experimental
description: Participants will receive four cycles of TCHP [docetaxel (Taxotere®, carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who have residual disease may be offered two more cycles of TCHP in the adjuvant settings (optional) per treating oncologist's discretion and then will receive infusion of Trastuzumab Emtansine (TDM1) plus pertuzumab every three weeks for a total of 12 cycles/infusions.
intervention type: Drug
intervention name: Docetaxel
description: Dose: 75 mg/m2 q3w
arm group label: Pathologic complete response (pCR)
arm group label: Residual Disease
other name: Taxotere
intervention type: Drug
intervention name: Carboplatin
description: Dose: area under the concentration-time curve [AUC] 6 q3w
arm group label: Pathologic complete response (pCR)
arm group label: Residual Disease
other name: Paraplatin
intervention type: Drug
intervention name: Trastuzumab
description: Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w
arm group label: Pathologic complete response (pCR)
arm group label: Residual Disease
other name: Herceptin
intervention type: Drug
intervention name: Pertuzumab
description: Dose: 840-mg loading dose, 420-mg maintenance dose q3w
arm group label: Pathologic complete response (pCR)
arm group label: Residual Disease
other name: Perjeta
intervention type: Drug
intervention name: Trastuzumab emtansine
description: Dose: 3.6mg/kg q3w
arm group label: Residual Disease
other name: TDM1
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajay Dhakal, MBBS
role: Principal Investigator
affiliation: University of Rochester
last name: Ajay Dhakal, MBBS
phone: 585-275-5863
email: Ajay_Dhakal@urmc.rochester.edu
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Ajay Dhakal
investigator title: Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)
mesh term: Breast Neoplasms
mesh term: Carboplatin
mesh term: Docetaxel
mesh term: Trastuzumab
mesh term: Pertuzumab
mesh term: Maytansine
mesh term: Ado-Trastuzumab Emtansine