<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/NCT03025711</url>
  </required_header>
  <id_info>
    <org_study_id>ML29844</org_study_id>
    <nct_id>NCT03025711</nct_id>
  </id_info>
  <brief_title>Outcomes Of The Spanish Cohort Of Early Access To Pertuzumab And Trastuzumab Emtansine</brief_title>
  <acronym>KNOWHER</acronym>
  <official_title>Use Of Pertuzumab And Trastuzumab Emtansine In Adult Patients With Her2-Positive Metastatic Or Locally Recurrent Unresectable Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BELEN RUIZ-ANTORAN</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Puerta de Hierro University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall study objective is to evaluate the effectiveness and safety of Trastuzumab&#xD;
      emtansine (T-DM1) and Pertuzumab under real-world disease conditions in the Spain, and&#xD;
      specifically in patients treated under compassionate use or early access program&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective, non-interventional, non-comparative, observational cohort study /&#xD;
      registry in the Spain. The study design will reflect real-life clinical management of&#xD;
      patients with HER2-positive MBC. Type and frequency of actual patient visits and all&#xD;
      evaluations will be done as for routine clinical practice.&#xD;
&#xD;
      The analysis of the efficacy and safety results obtained in patients receiving pertuzumab or&#xD;
      TDM1 in those early access systems is of utmost importance. These real-world patients with&#xD;
      advanced breast cancer may have different characteristics than those enrolled in clinical&#xD;
      trials and clinicians must often extrapolate into therapeutic decisions not fully supported&#xD;
      by a robust evidence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">January 31, 2020</completion_date>
  <primary_completion_date type="Actual">October 1, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival.</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of death from any cause, assessed up to 48 months).</time_frame>
    <description>The time between the date of start of treatment and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival.</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of first documented progression assessed up to 48 months)</time_frame>
    <description>The time from start of treatment to the date of the first documented tumour progression as determined by the clinician (may be based on clinical examination or radiographic or laboratory features).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response rate</measure>
    <time_frame>Through study completion, an average of 4 year</time_frame>
    <description>Response rate is defined as the proportion of patients with complete response (CR) or partial response (PR) based on their best overall response as written in the medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Through study completion, an average of 4 year</time_frame>
    <description>The time between the date of first confirmed response to the date of the first documented tumour progression, or death due to any cause, whichever occurs first. At the time of the analysis, several limitations should be taken into consideration for this retrospective study: DOR is only appraisable if measurable disease and DOR data availability in the medical records (ideally assessed with the RECIST criteria) could be incomplete.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of treatment failure, assessed up to 48 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Objective Response</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of the first confirmed response, assessed up to 48 months)</time_frame>
    <description>The time from start of treatment to the date of the first confirmed response (evaluated for responders only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to change treatment</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of change treatment, assessed up to 48 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next treatment</measure>
    <time_frame>Through study completion (from date of start of treatment until the date of start other treatment, assessed up to 48 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All suspected Grade 3/4/5 adverse reactions</measure>
    <time_frame>Through study completion, an average of 4 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events of special interest to anti HER2 Mab (AESI)</measure>
    <time_frame>Through study completion, an average of 4 year</time_frame>
    <description>AESIs regarding treatment with T-DM1: Hepatic disorder (specific analytical alteration)&#xD;
AESIs regarding treatment with Pertuzumab: Interstitial Lung Disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AEs of scientific interest</measure>
    <time_frame>Through study completion, an average of 4 year</time_frame>
    <description>An asymptomatic decline in LVEF requiring treatment or leading to discontinuation of study treatment (regarding treatment with T-DM1 and Pertuzumab)&#xD;
Other AEs leading to treatment discontinuation</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">220</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Pertuzumab</arm_group_label>
    <description>Patients with HER2-positive metastatic or locally recurrent unresectable breast cancer and who are treated with Pertuzumab under Spanish compassionate use or early access program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Trastuzumab emtansine</arm_group_label>
    <description>Patients with HER2-positive metastatic or locally recurrent unresectable breast cancer and who are treated with Trastuzumab emtansine (T-DM1) under Spanish compassionate use or early access program</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        This study will include a cohort of approximately 700 adult patients from the Spain with&#xD;
        HER2-positive metastatic or locally recurrent unresectable breast cancer and who are&#xD;
        treated with Trastuzumab emtansine (T-DM1) or Pertuzumab under compassionate use or early&#xD;
        access program. The decision to initiate use of Trastuzumab emtansine (T-DM1) and&#xD;
        Pertuzumab is made independently by the participant and their health care provider and is&#xD;
        not mandated by the study design or protocol.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (age ≥ 18 years at enrolment) with HER2-positive metastatic or locally&#xD;
             recurrent unresectable breast cancer and who are treated with Trastuzumab emtansine&#xD;
             (T-DM1) or Pertuzumab.&#xD;
&#xD;
          -  Patients who initiate Trastuzumab emtansine (T-DM1) and Pertuzumab under Spanish&#xD;
             compassionate use or early access program.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Given the characteristics of the study there are no exclusion criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Belén Ruiz-Antorán, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Clinical Pharmacology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Puerta de Hierro University Hospital</name>
      <address>
        <city>Madrid</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>March 4, 2020</last_update_submitted>
  <last_update_submitted_qc>March 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Puerta de Hierro University Hospital</investigator_affiliation>
    <investigator_full_name>BELEN RUIZ-ANTORAN</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Advanced HER2+ breast cancer</keyword>
  <keyword>Pertuzumab</keyword>
  <keyword>Trastuzumab emtansine</keyword>
  <keyword>Compassionate use</keyword>
  <keyword>Early access program</keyword>
  <keyword>Effectiveness</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_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/NCT03025711
org study id: ML29844
nct id: NCT03025711
lead sponsor: 
has dmc: No
The overall study objective is to evaluate the effectiveness and safety of Trastuzumab
      emtansine (T-DM1) and Pertuzumab under real-world disease conditions in the Spain, and
      specifically in patients treated under compassionate use or early access program
This is a retrospective, non-interventional, non-comparative, observational cohort study /
      registry in the Spain. The study design will reflect real-life clinical management of
      patients with HER2-positive MBC. Type and frequency of actual patient visits and all
      evaluations will be done as for routine clinical practice.

      The analysis of the efficacy and safety results obtained in patients receiving pertuzumab or
      TDM1 in those early access systems is of utmost importance. These real-world patients with
      advanced breast cancer may have different characteristics than those enrolled in clinical
      trials and clinicians must often extrapolate into therapeutic decisions not fully supported
      by a robust evidence.
observational model: Cohort
time perspective: Retrospective
measure: Overall survival.
time frame: Through study completion (from date of start of treatment until the date of death from any cause, assessed up to 48 months).
description: The time between the date of start of treatment and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive
measure: Progression free survival.
time frame: Through study completion (from date of start of treatment until the date of first documented progression assessed up to 48 months)
description: The time from start of treatment to the date of the first documented tumour progression as determined by the clinician (may be based on clinical examination or radiographic or laboratory features).
measure: Best overall response rate
time frame: Through study completion, an average of 4 year
description: Response rate is defined as the proportion of patients with complete response (CR) or partial response (PR) based on their best overall response as written in the medical record
measure: Duration of response (DOR)
time frame: Through study completion, an average of 4 year
description: The time between the date of first confirmed response to the date of the first documented tumour progression, or death due to any cause, whichever occurs first. At the time of the analysis, several limitations should be taken into consideration for this retrospective study: DOR is only appraisable if measurable disease and DOR data availability in the medical records (ideally assessed with the RECIST criteria) could be incomplete.
measure: Time to treatment failure
time frame: Through study completion (from date of start of treatment until the date of treatment failure, assessed up to 48 months)
measure: Time to Objective Response
time frame: Through study completion (from date of start of treatment until the date of the first confirmed response, assessed up to 48 months)
description: The time from start of treatment to the date of the first confirmed response (evaluated for responders only)
measure: Time to change treatment
time frame: Through study completion (from date of start of treatment until the date of change treatment, assessed up to 48 months)
measure: Time to next treatment
time frame: Through study completion (from date of start of treatment until the date of start other treatment, assessed up to 48 months)
measure: All suspected Grade 3/4/5 adverse reactions
time frame: Through study completion, an average of 4 year
measure: Adverse events of special interest to anti HER2 Mab (AESI)
time frame: Through study completion, an average of 4 year
description: AESIs regarding treatment with T-DM1: Hepatic disorder (specific analytical alteration)
AESIs regarding treatment with Pertuzumab: Interstitial Lung Disease
measure: AEs of scientific interest
time frame: Through study completion, an average of 4 year
description: An asymptomatic decline in LVEF requiring treatment or leading to discontinuation of study treatment (regarding treatment with T-DM1 and Pertuzumab)
Other AEs leading to treatment discontinuation
arm group label: Pertuzumab
description: Patients with HER2-positive metastatic or locally recurrent unresectable breast cancer and who are treated with Pertuzumab under Spanish compassionate use or early access program
arm group label: Trastuzumab emtansine
description: Patients with HER2-positive metastatic or locally recurrent unresectable breast cancer and who are treated with Trastuzumab emtansine (T-DM1) under Spanish compassionate use or early access program
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Belén Ruiz-Antorán, PhD
role: Principal Investigator
affiliation: Department of Clinical Pharmacology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain
facility: 
country: Spain
responsible party type: Sponsor-Investigator
investigator affiliation: Puerta de Hierro University Hospital
investigator full name: BELEN RUIZ-ANTORAN
investigator title: Principal Investigator
mesh term: Breast Neoplasms
sharing ipd: No