<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/NCT01669239</url>
  </required_header>
  <id_info>
    <org_study_id>SOLTI-1002</org_study_id>
    <secondary_id>2012-001201-24</secondary_id>
    <nct_id>NCT01669239</nct_id>
  </id_info>
  <brief_title>Study of Neoadjuvant Myocet®, Paclitaxel, Pertuzumab, and Trastuzumab in HER2-positive Breast Cancer</brief_title>
  <acronym>Opti-HER</acronym>
  <official_title>OptiHER-Heart: A Prospective, Multicenter, Single-arm, Phase II Study to Evaluate the Safety of Neoadjuvant Liposomal Doxorubicin (Myocet®) Plus Paclitaxel, Trastuzumab, and Pertuzumab in Patients With HER2-positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SOLTI Breast Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SOLTI Breast Cancer Research Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, multicenter, single-arm, phase II study to evaluate the safety of&#xD;
      neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients&#xD;
      with HER2-positive breast cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of symptomatic (type A) and asymptomatic (type B) cardiac events during the study treatment period</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>pCR in breast (pCRB)</measure>
    <time_frame>At the time of definitive surgery, an expected average of 23 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR in breast and axilla (pCRBA)</measure>
    <time_frame>At the time of definitive surgery, an expected average of 23 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical objective response rate (cORR) in the breast and axilla by RECIST criteria version 1.1</measure>
    <time_frame>At the time of definitive surgery, an expected average of 23 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual Cancer Burden (RCB) at surgery following the procedures of the MD Anderson Cancer Center</measure>
    <time_frame>At the time of definitive surgery, an expected average of 23 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breast conservation rate at surgery</measure>
    <time_frame>At the time of definitive surgery, an expected average of 23 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of serum biomarkers predictive of cardiotoxicity</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4)</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of onset and time of recovery from symptomatic (type A) and asymptomatic (type B) cardiac events (assessed by CTCAE v.4)</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose reductions due to treatment toxicity (assessed by CTCAE v.4)</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose delays due to treatment toxicity (assessed by CTCAE v.4)</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events and serious adverse events (assessed by CTCAE v.4)</measure>
    <time_frame>Following 12 months after first dose of the study treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Liposomal Doxorubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Six cycles of:&#xD;
Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks&#xD;
Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks&#xD;
Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks&#xD;
Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal Doxorubicin</intervention_name>
    <description>Six cycles of:&#xD;
Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks&#xD;
Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks&#xD;
Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks&#xD;
Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks</description>
    <arm_group_label>Liposomal Doxorubicin</arm_group_label>
    <other_name>Myocet® (liposome-encapsulated doxorubicin)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent for all study procedures according to local regulatory&#xD;
             requirements prior to beginning specific protocol procedures&#xD;
&#xD;
          -  Female patients&#xD;
&#xD;
          -  Age 18-74 years&#xD;
&#xD;
          -  ECOG Performance Status of 0 or 1&#xD;
&#xD;
          -  Histologically confirmed, untreated, invasive breast carcinoma stage II-IIIB&#xD;
&#xD;
          -  Tumor size &gt; 2 cm by clinical or radiological assessment&#xD;
&#xD;
          -  HER2+ invasive BC according to ASCO/CAP guidelines&#xD;
&#xD;
          -  Known hormone receptor status or the possibility of its assessment&#xD;
&#xD;
          -  Adequate organ function defined as:&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥ 1.5 x 10**9/L&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≥ 9 g/dL&#xD;
&#xD;
               -  Platelets &gt; 100 x 10**9/L&#xD;
&#xD;
               -  Creatinine ≤ 1.6 mg/dL&#xD;
&#xD;
               -  ALT and AST ≤ 2.5 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 5 ULN&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 mg/dL&#xD;
&#xD;
          -  Baseline LVEF ≥ 55% measured by echocardiogram or MUGA scan&#xD;
&#xD;
          -  Negative β-HCG pregnancy test (serum) for premenopausal women of reproductive capacity&#xD;
             (those who are biologically capable of having children) and for women less than 12&#xD;
             months after the menopause. All subjects who are biologically capable of having&#xD;
             children must agree and commit to the use of a reliable method of birth control from 2&#xD;
             weeks before administration of the first dose of investigational product until 28 days&#xD;
             after the last dose of investigational product&#xD;
&#xD;
          -  Absence of any psychological, familial, sociological, or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule; those&#xD;
             conditions should be discussed with the patient before registration in the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical or radiologic evidence of metastatic disease at the time of study entry&#xD;
&#xD;
          -  Prior chemotherapy, radiotherapy, or surgery for BC, other than excision of a tumor in&#xD;
             the contralateral breast, and provided that the patient did not previously receive&#xD;
             adjuvant radiotherapy or chemotherapy&#xD;
&#xD;
          -  Subjects with a concurrently active second malignancy, other than adequately treated&#xD;
             non melanoma skin cancers, in situ melanoma or in situ cervical cancer. Subjects with&#xD;
             other non-mammary malignancies must have been disease-free for at least 5 years&#xD;
&#xD;
          -  Known or suspected hypersensitivity reaction to any investigational or therapeutic&#xD;
             compound or their incorporated substances&#xD;
&#xD;
          -  Presence of CHF or LVEF &lt; 55%&#xD;
&#xD;
          -  Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular&#xD;
             accident (&lt; 6 months before enrollment), unstable angina pectoris, myocardial&#xD;
             infarction ≤ 6 months before enrollment, uncontrolled hypertension (systolic &gt; 150&#xD;
             mmHg and/or diastolic &gt; 100 mmHg), or high-risk uncontrolled arrhythmias&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus, active peptic ulcer disease, or uncontrolled epilepsy&#xD;
&#xD;
          -  Active uncontrolled infection at the time of enrolment&#xD;
&#xD;
          -  History of significant co-morbidities that, in the judgment of the investigator, may&#xD;
             interfere with the conduction of the study, the evaluation of response, or with&#xD;
             informed consent&#xD;
&#xD;
          -  Use of any investigational agent or participation in another therapeutic clinical&#xD;
             trial concurrently or in the previous 30 days before the enrollment&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding&#xD;
&#xD;
          -  Women of child-bearing potential who are unable or unwilling to use acceptable&#xD;
             contraceptive measures&#xD;
&#xD;
          -  Inability or unwillingness to abide by the study protocol or cooperate fully with the&#xD;
             investigator or designee&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joaquín Gavilá Gregori, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundación Instituto Valenciano de Oncología</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d´Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario San Pedro de Alcántara</name>
      <address>
        <city>Cáceres</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova de Lleida</name>
      <address>
        <city>Lleida</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncológico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro de Majadahonda</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center Madrid</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Son Llàtzer</name>
      <address>
        <city>Palma de Mallorca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Reus</name>
      <address>
        <city>Reus</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sagrado Corazón USP</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Macarena</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundación Instituto Valenciano de Oncología</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova de Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Lozano Blesa</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.gruposolti.org</url>
    <description>SOLTI Breast Cancer Research Group</description>
  </link>
  <reference>
    <citation>Gavilá J, Llombart A, Guerrero A, Ruíz A, Climent M, Guillem V. Opti-HER HEART: A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.</citation>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>October 31, 2017</last_update_submitted>
  <last_update_submitted_qc>October 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>HER2 positive</keyword>
  <keyword>Neoadjuvant</keyword>
  <keyword>Liposomal doxorubicin</keyword>
  <keyword>Paclitaxel</keyword>
  <keyword>Trastuzumab</keyword>
  <keyword>Pertuzumab</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</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/NCT01669239
org study id: SOLTI-1002
secondary id: 2012-001201-24
nct id: NCT01669239
lead sponsor: 
has dmc: Yes
This is a prospective, multicenter, single-arm, phase II study to evaluate the safety of
      neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients
      with HER2-positive breast cancer
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of symptomatic (type A) and asymptomatic (type B) cardiac events during the study treatment period
time frame: Following 12 months after first dose of the study treatment
measure: pCR in breast (pCRB)
time frame: At the time of definitive surgery, an expected average of 23 weeks
measure: pCR in breast and axilla (pCRBA)
time frame: At the time of definitive surgery, an expected average of 23 weeks
measure: Clinical objective response rate (cORR) in the breast and axilla by RECIST criteria version 1.1
time frame: At the time of definitive surgery, an expected average of 23 weeks
measure: Residual Cancer Burden (RCB) at surgery following the procedures of the MD Anderson Cancer Center
time frame: At the time of definitive surgery, an expected average of 23 weeks
measure: Breast conservation rate at surgery
time frame: At the time of definitive surgery, an expected average of 23 weeks
measure: Evaluation of serum biomarkers predictive of cardiotoxicity
time frame: Following 12 months after first dose of the study treatment
measure: Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4)
time frame: Following 12 months after first dose of the study treatment
measure: Time of onset and time of recovery from symptomatic (type A) and asymptomatic (type B) cardiac events (assessed by CTCAE v.4)
time frame: Following 12 months after first dose of the study treatment
measure: Dose reductions due to treatment toxicity (assessed by CTCAE v.4)
time frame: Following 12 months after first dose of the study treatment
measure: Dose delays due to treatment toxicity (assessed by CTCAE v.4)
time frame: Following 12 months after first dose of the study treatment
measure: Number of patients with adverse events and serious adverse events (assessed by CTCAE v.4)
time frame: Following 12 months after first dose of the study treatment
arm group label: Liposomal Doxorubicin
arm group type: Experimental
description: Six cycles of:
Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks
Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks
Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks
Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks
intervention type: Drug
intervention name: Liposomal Doxorubicin
description: Six cycles of:
Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks
Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks
Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks
Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks
arm group label: Liposomal Doxorubicin
other name: Myocet® (liposome-encapsulated doxorubicin)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Joaquín Gavilá Gregori, MD
role: Principal Investigator
affiliation: Fundación Instituto Valenciano de Oncología
facility: 
facility: 
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facility: 
facility: 
facility: 
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country: Spain
url: http://www.gruposolti.org
description: SOLTI Breast Cancer Research Group
citation: Gavilá J, Llombart A, Guerrero A, Ruíz A, Climent M, Guillem V. Opti-HER HEART: A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin