<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/NCT02194166</url>
  </required_header>
  <id_info>
    <org_study_id>ML28839</org_study_id>
    <nct_id>NCT02194166</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Tolerability of Subcutaneous (SC) Trastuzumab Administration in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Early Breast Cancer (eBC) Using Either a Single-Use Injection Device or Manual Administration</brief_title>
  <acronym>ESCAPE</acronym>
  <official_title>An Open-Label, Randomized, Cross-Over, Multicenter, Phase IIIb Study, to Assess Patients' Tolerability of Trastuzumab Administrated Subcutaneously (SC) Either Via a Single Use Injection Device (SID) or Via Vial for Manual Administration (SC Vial) in Patients With HER2-Positive Early Breast Cancer (eBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This multicenter study in participants with HER2-positive eBC will investigate participants'&#xD;
      pain and discomfort of SC trastuzumab (Herceptin) administered either via a single-use&#xD;
      injection device (SID) or via vial for manual administration using a hand-held syringe (SC&#xD;
      vial). In total, participants will obtain at least 18 cycles/1 year of trastuzumab (4 cycles&#xD;
      of intravenous [IV] and 14 cycles of SC trastuzumab).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2014</start_date>
  <completion_date type="Actual">July 12, 2018</completion_date>
  <primary_completion_date type="Actual">July 12, 2018</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Participant Pain as Measured on a 10 Centimeter (cm) Visual Analogue Scale</measure>
    <time_frame>Week 13 up to Week 52</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Participant Discomfort as Measured on a 10 cm Visual Analogue Scale</measure>
    <time_frame>Week 13 up to Week 52</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Healthcare Professional Satisfaction With SC Formulation as Assessed by Health Care Professional Questionnaire (HCPQ)</measure>
    <time_frame>Week 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction With SC Formulation as Assessed by Patients Satisfaction Questionnaire (PSQ)</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Healthcare Professional Perceived Time Savings With SC Trastuzumab as Assessed by HCPQ</measure>
    <time_frame>Week 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Baseline up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From first study treatment to death from any cause, assessed up to approximately 4.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-Free Survival, Assessed as per Institutional Practice or American Society of Clinical Oncology (ASCO) Adjuvant Follow-up Guidelines 2006</measure>
    <time_frame>From first study treatment to documented disease progression or death, assessed up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Days on Trastuzumab Treatment</measure>
    <time_frame>Week 1 up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Daily Dose of Trastuzumab</measure>
    <time_frame>Week 1 up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Dose of Trastuzumab</measure>
    <time_frame>Week 1 up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Treatment</measure>
    <time_frame>Week 1 up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Safety Observation</measure>
    <time_frame>28 days after last study treatment (up to Week 56)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Follow-Up</measure>
    <time_frame>25 months after last study treatment (up to 3 years)</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Pre-Randomization (Trastuzumab IV)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trastuzumab IV will be given during the first 4 cycles for all participants before randomization for SC administration. A dose of 6 milligrams per kilogram (mg/kg) will be given every 3 weeks. All the participants will require a loading dose on Day 1 of Cycle 1, so they will receive 8 mg/kg followed by 6 mg/kg, 3 weeks later and then 3-weekly. Concurrent administration during the first 4 cycles of trastuzumab IV with paclitaxel/docetaxel will have to be performed in accordance with local hospital practice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group A: Trastuzumab SC (First Vial Formulation, then SID)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 7 cycles of SC trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation) followed by 7 cycles of SC trastuzumab 600 mg SID administration after cross-over.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: Trastuzumab SC (First SID, then Vial Formulation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will start with 7 cycles of SC trastuzumab 600 mg administration via SID and after cross-over will receive 7 injections of trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Trastuzumab IV or SC will be administered as described.</description>
    <arm_group_label>Group A: Trastuzumab SC (First Vial Formulation, then SID)</arm_group_label>
    <arm_group_label>Group B: Trastuzumab SC (First SID, then Vial Formulation)</arm_group_label>
    <arm_group_label>Pre-Randomization (Trastuzumab IV)</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel will be administered in accordance with local hospital practice.</description>
    <arm_group_label>Pre-Randomization (Trastuzumab IV)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel will be administered in accordance with local hospital practice.</description>
    <arm_group_label>Pre-Randomization (Trastuzumab IV)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Hormonal therapy allowed as per institutional guidelines&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) of greater than or equal to (&gt;/=) 55 percent&#xD;
             (%) measured by echocardiography (ECHO) prior to first dose of trastuzumab&#xD;
&#xD;
          -  HER2-positive disease immunohistochemistry (IHC) 3+ or in-situ hybridization (ISH)&#xD;
             positive as determined in a local laboratory that is experienced/certified in&#xD;
             HER2-expression testing using an accurate and validated assay&#xD;
&#xD;
          -  Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast&#xD;
&#xD;
          -  No evidence of residual, locally recurrent or metastatic disease after completion of&#xD;
             surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant)&#xD;
&#xD;
          -  Participants who have completed all (neo)adjuvant treatment or participants after&#xD;
             adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC) to whom the 4&#xD;
             subsequent cycles of trastuzumab in combination with paclitaxel or docetaxel are&#xD;
             indicated per local practice&#xD;
&#xD;
          -  Not more than 3 months should have elapsed since the last dose of adjuvant&#xD;
             chemotherapy in case of subsequent treatment scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous neoadjuvant or adjuvant breast cancer treatment with an approved or&#xD;
             investigational anti-HER2 agent&#xD;
&#xD;
          -  History of other malignancy that can affect compliance with the protocol or&#xD;
             interpretation of results. Participants with curatively treated carcinoma in situ of&#xD;
             the cervix or basal cell carcinoma, and participants with other curatively treated&#xD;
             malignancies who have been disease-free for at least 5 years, are eligible.&#xD;
             Participants with previous ductal carcinoma in situ (DCIS) of the breast are also&#xD;
             eligible for the study&#xD;
&#xD;
          -  Participants with severe dyspnea at rest or requiring supplementary oxygen therapy&#xD;
&#xD;
          -  Participants with other concurrent serious diseases that may interfere with planned&#xD;
             treatment, including severe pulmonary conditions/illness&#xD;
&#xD;
          -  Prior maximum cumulative dose of doxorubicin &gt;360 mg/m2 or maximum cumulative dose of&#xD;
             epirubicin &gt;720 mg/m2 or equivalent&#xD;
&#xD;
          -  Serious cardiac illness or medical conditions that would preclude the use of&#xD;
             trastuzumab, specifically: history of documented congestive heart failure (CHF),&#xD;
             high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically&#xD;
             significant valvular disease, evidence of transmural infarction on electrocardiogram&#xD;
             (ECG), diagnosed poorly controlled hypertension&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus (HIV), active hepatitis B virus&#xD;
             (HBV) or hepatitis C virus (HCV)&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Concurrent enrollment in another clinical trial using an investigational anticancer&#xD;
             treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy,&#xD;
             within 28 days prior to the first dose of study treatment&#xD;
&#xD;
          -  Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of&#xD;
             Herceptin®, or the adhesive of the SC device, or a history of severe allergic or&#xD;
             immunological reactions, e.g., difficult to control asthma&#xD;
&#xD;
          -  Inadequate bone marrow, hepatic, or renal function&#xD;
&#xD;
          -  Major surgical procedure or significant traumatic injury within 14 days prior to the&#xD;
             first dose of study treatment or anticipated need for major surgery during the course&#xD;
             of study treatment&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State Inst N.N. Alexandrov Republican Scientific &amp; Practical Centre of Oncology &amp; Medical Radiology</name>
      <address>
        <city>A/g Lesnoy, Minsk Region</city>
        <zip>223040</zip>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthcare Institution &quot;Brest Regional Oncologic Dispensary&quot;</name>
      <address>
        <city>Brest</city>
        <zip>224027</zip>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minsk City Clinical Oncologic Dispensary</name>
      <address>
        <city>Minsk</city>
        <zip>BU-220013</zip>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vitebsk Regional Clinical Oncology Dispensary</name>
      <address>
        <city>Vitebsk</city>
        <zip>BU-210603</zip>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department</name>
      <address>
        <city>Almaty</city>
        <zip>050022</zip>
        <country>Kazakhstan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Almaty Cancer Hospital; Chemotherapy department</name>
      <address>
        <city>Almaty</city>
        <zip>050054</zip>
        <country>Kazakhstan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology centre of Astana; Chemotherapy department</name>
      <address>
        <city>Astana</city>
        <zip>010000</zip>
        <country>Kazakhstan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belarus</country>
    <country>Kazakhstan</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>June 6, 2019</last_update_submitted>
  <last_update_submitted_qc>June 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 10, 2019</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>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>Docetaxel</mesh_term>
    <mesh_term>Trastuzumab</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/NCT02194166
org study id: ML28839
nct id: NCT02194166
lead sponsor: 
This multicenter study in participants with HER2-positive eBC will investigate participants'
      pain and discomfort of SC trastuzumab (Herceptin) administered either via a single-use
      injection device (SID) or via vial for manual administration using a hand-held syringe (SC
      vial). In total, participants will obtain at least 18 cycles/1 year of trastuzumab (4 cycles
      of intravenous [IV] and 14 cycles of SC trastuzumab).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Participant Pain as Measured on a 10 Centimeter (cm) Visual Analogue Scale
time frame: Week 13 up to Week 52
measure: Participant Discomfort as Measured on a 10 cm Visual Analogue Scale
time frame: Week 13 up to Week 52
measure: Healthcare Professional Satisfaction With SC Formulation as Assessed by Health Care Professional Questionnaire (HCPQ)
time frame: Week 22
measure: Patient Satisfaction With SC Formulation as Assessed by Patients Satisfaction Questionnaire (PSQ)
time frame: Week 52
measure: Healthcare Professional Perceived Time Savings With SC Trastuzumab as Assessed by HCPQ
time frame: Week 22
measure: Percentage of Participants With Adverse Events
time frame: Baseline up to approximately 3 years
measure: Overall Survival
time frame: From first study treatment to death from any cause, assessed up to approximately 4.5 years
measure: Disease-Free Survival, Assessed as per Institutional Practice or American Society of Clinical Oncology (ASCO) Adjuvant Follow-up Guidelines 2006
time frame: From first study treatment to documented disease progression or death, assessed up to approximately 3 years
measure: Number of Days on Trastuzumab Treatment
time frame: Week 1 up to Week 52
measure: Total Daily Dose of Trastuzumab
time frame: Week 1 up to Week 52
measure: Cumulative Dose of Trastuzumab
time frame: Week 1 up to Week 52
measure: Duration of Treatment
time frame: Week 1 up to Week 52
measure: Duration of Safety Observation
time frame: 28 days after last study treatment (up to Week 56)
measure: Duration of Follow-Up
time frame: 25 months after last study treatment (up to 3 years)
arm group label: Pre-Randomization (Trastuzumab IV)
arm group type: Experimental
description: Trastuzumab IV will be given during the first 4 cycles for all participants before randomization for SC administration. A dose of 6 milligrams per kilogram (mg/kg) will be given every 3 weeks. All the participants will require a loading dose on Day 1 of Cycle 1, so they will receive 8 mg/kg followed by 6 mg/kg, 3 weeks later and then 3-weekly. Concurrent administration during the first 4 cycles of trastuzumab IV with paclitaxel/docetaxel will have to be performed in accordance with local hospital practice.
arm group label: Group A: Trastuzumab SC (First Vial Formulation, then SID)
arm group type: Experimental
description: Participants will receive 7 cycles of SC trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation) followed by 7 cycles of SC trastuzumab 600 mg SID administration after cross-over.
arm group label: Group B: Trastuzumab SC (First SID, then Vial Formulation)
arm group type: Experimental
description: Participants will start with 7 cycles of SC trastuzumab 600 mg administration via SID and after cross-over will receive 7 injections of trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation).
intervention type: Drug
intervention name: Trastuzumab
description: Trastuzumab IV or SC will be administered as described.
arm group label: Group A: Trastuzumab SC (First Vial Formulation, then SID)
arm group label: Group B: Trastuzumab SC (First SID, then Vial Formulation)
arm group label: Pre-Randomization (Trastuzumab IV)
other name: Herceptin
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel will be administered in accordance with local hospital practice.
arm group label: Pre-Randomization (Trastuzumab IV)
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel will be administered in accordance with local hospital practice.
arm group label: Pre-Randomization (Trastuzumab IV)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belarus
country: Kazakhstan
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Docetaxel
mesh term: Trastuzumab