<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/NCT03767335</url>
  </required_header>
  <id_info>
    <org_study_id>MEN1611-01</org_study_id>
    <secondary_id>2017-004631-36</secondary_id>
    <nct_id>NCT03767335</nct_id>
  </id_info>
  <brief_title>MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer</brief_title>
  <acronym>B-PRECISE-01</acronym>
  <official_title>Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast Cancer Progressed to Anti-HER2 Based Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Menarini Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Menarini Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this open-label, dose-escalation, phase Ib study is to identify the&#xD;
      appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without&#xD;
      Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses&#xD;
      MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients&#xD;
      affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to&#xD;
      the post-menopausal patients with hormone-sensitive disease.&#xD;
&#xD;
      MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide&#xD;
      3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given&#xD;
      as single agent was assessed in a phase I trial in patients with advanced solid tumors.&#xD;
&#xD;
      This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611&#xD;
      given in combination with Trastuzumab with/without Fulvestrant.&#xD;
&#xD;
      The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor&#xD;
      activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review&#xD;
      Committee.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 19, 2018</start_date>
  <completion_date type="Anticipated">December 21, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 21, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D)</measure>
    <time_frame>28 Days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment emergent adverse events (TEAEs)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Advanced or Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>MEN1611</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEN1611 + Trastuzumab +/- Fulvestrant</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEN1611</intervention_name>
    <description>MEN1611 oral dose administered twice daily for a continuous 28-day cycle</description>
    <arm_group_label>MEN1611</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Trastuzumab solution for infusion administered weekly via IV</description>
    <arm_group_label>MEN1611</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant</intervention_name>
    <description>Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)</description>
    <arm_group_label>MEN1611</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed invasive adenocarcinoma of the breast&#xD;
&#xD;
          -  Known HER2+ breast cancer&#xD;
&#xD;
          -  Advanced or metastatic breast cancer harbouring PIK3CA mutation on tissue sample&#xD;
&#xD;
          -  &gt; 2 lines of anti-HER2 based regimens with at least 1 regimen with trastuzumab&#xD;
&#xD;
          -  Radiological documented evidence of progressive disease&#xD;
&#xD;
          -  Life expectancy ≥ 12 weeks&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with PI3K inhibitors&#xD;
&#xD;
          -  Brain metastases untreated, unless treated &gt; 4 weeks and only if clinically stable and&#xD;
             not receiving corticosteroids&#xD;
&#xD;
          -  History of clinically significant bowel disease&#xD;
&#xD;
          -  ≥ grade 2 diarrhoea&#xD;
&#xD;
          -  History of significant, uncontrolled, or active cardiovascular disease&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing psychiatric or neurologic illness or other&#xD;
             conditions that could interfere with patient's safety&#xD;
&#xD;
          -  Not controlled diabetes mellitus (glycated haemoglobin [HbA1c] &gt;7%) and fasting plasma&#xD;
             glucose &gt;126 mg/dL&#xD;
&#xD;
          -  Concurrent chronic treatment with steroids, as immunosuppressant, or another&#xD;
             immunosuppressive agent&#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>Martine Piccart, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Holy Cross Hospital Inc.</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Detroit Clinical Research Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Jules Bordet</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Régional du Cancer de Montpellier</name>
      <address>
        <city>Montferrier Sur Lez</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO - Site René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud Oncopole</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Mater Domini</name>
      <address>
        <city>Catanzaro</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia (IEO)</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic i Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Madrid Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</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>Velindre Cancer Centre</name>
      <address>
        <city>Cardiff</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute UK</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>May 23, 2023</last_update_submitted>
  <last_update_submitted_qc>May 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced Breast Cancer</keyword>
  <keyword>Metastatic Breast Cancer</keyword>
  <keyword>PI3K inhibitor</keyword>
  <keyword>HER2-positive</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>Trastuzumab</mesh_term>
    <mesh_term>Fulvestrant</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/NCT03767335
org study id: MEN1611-01
secondary id: 2017-004631-36
nct id: NCT03767335
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The main purpose of this open-label, dose-escalation, phase Ib study is to identify the
      appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without
      Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer
This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses
      MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients
      affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to
      the post-menopausal patients with hormone-sensitive disease.

      MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide
      3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given
      as single agent was assessed in a phase I trial in patients with advanced solid tumors.

      This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611
      given in combination with Trastuzumab with/without Fulvestrant.

      The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor
      activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review
      Committee.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D)
time frame: 28 Days
measure: Treatment emergent adverse events (TEAEs)
time frame: 2 years
measure: Progression Free Survival
time frame: 2 years
measure: Overall Survival
time frame: 2 years
arm group label: MEN1611
arm group type: Experimental
description: MEN1611 + Trastuzumab +/- Fulvestrant
intervention type: Drug
intervention name: MEN1611
description: MEN1611 oral dose administered twice daily for a continuous 28-day cycle
arm group label: MEN1611
intervention type: Drug
intervention name: Trastuzumab
description: Trastuzumab solution for infusion administered weekly via IV
arm group label: MEN1611
intervention type: Drug
intervention name: Fulvestrant
description: Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)
arm group label: MEN1611
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martine Piccart, MD PhD
role: Study Chair
affiliation: Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium
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country: Belgium
country: France
country: Italy
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Trastuzumab
mesh term: Fulvestrant