<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/NCT04495621</url>
  </required_header>
  <id_info>
    <org_study_id>MEN1611-02</org_study_id>
    <secondary_id>2019-003727-38</secondary_id>
    <nct_id>NCT04495621</nct_id>
  </id_info>
  <brief_title>MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)</brief_title>
  <acronym>C-PRECISE-01</acronym>
  <official_title>Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens</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>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open-label, dose-confirmation and cohort expansion, multicentre, Phase Ib/II study to assess&#xD;
      the anti-tumour activity and safety of MEN1611 in combination with cetuximab for the&#xD;
      treatment of patients with PIK3CA mutated metastatic colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase Ib/II study will investigate the anti-tumour activity and safety of daily oral&#xD;
      doses MEN1611 in combination with cetuximab in female and male patients affected by PIK3CA&#xD;
      mutated, N-K-RAS wild-type and BRAF wild-type metastatic colorectal cancer.&#xD;
&#xD;
      MEN1611 is a potent, selective Class I phosphoinositide 3-kinase (PI3K) inhibitor. The&#xD;
      Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial&#xD;
      in patients with advanced solid tumors.&#xD;
&#xD;
      This Phase Ib/II will start with a dose confirmation part (Step 1) to identify the RP2D of&#xD;
      MEN1611 given in combination with cetuximab.&#xD;
&#xD;
      The study will continue with a cohort expansion (Step 2) to explore the anti-tumour activity&#xD;
      of the selected MEN1611 dose level combined with cetuximab with further assessment of their&#xD;
      safety and tolerability.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</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: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of recommended phase II dose (RP2D)</measure>
    <time_frame>28 Days</time_frame>
    <description>Determination of the recommended phase II dose of MEN1611 when administered orally in combination with cetuximab to patients with PIK3CA mutated colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best overall response rate (ORR) according to RECIST v.1.1</measure>
    <time_frame>36 Months</time_frame>
    <description>Assessment of the anti-tumour activity of MEN1611 in combination with cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment emergent adverse events (TEAEs)</measure>
    <time_frame>36 Months</time_frame>
    <description>Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>MEN1611</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEN1611 + Cetuximab</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>Cetuximab</intervention_name>
    <description>Cetuximab solution for infusion administered weekly via IV infusion.</description>
    <arm_group_label>MEN1611</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Histological documentation of adenocarcinoma of the colon or rectum.&#xD;
&#xD;
          -  Progression or recurrence following prior irinotecan, oxaliplatin, 5-FU and anti-EGFR&#xD;
             containing regimens for metastatic disease.&#xD;
&#xD;
          -  Best response according to Response Evaluation Criteria in Solid Tumours criteria to&#xD;
             the last anti-EGFR containing regimen of partial response or stable disease for at&#xD;
             least 4 months.&#xD;
&#xD;
          -  Measurable disease according to RECIST criteria.&#xD;
&#xD;
          -  N-K-RAS (exons 2, 3 and 4) and BRAF wild-type and PIK3CA mutated.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with PI3K inhibitor.&#xD;
&#xD;
          -  Brain metastases, unless treated &gt; 4 weeks before Screening Visit and only if&#xD;
             clinically stable and not receiving corticosteroids.&#xD;
&#xD;
          -  NCI CTCAE v5.0 Grade ≥ 2 diarrhoea.&#xD;
&#xD;
          -  History of significant, uncontrolled or active cardiovascular disease.&#xD;
&#xD;
          -  Known active or uncontrolled pulmonary dysfunction.&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus (HbA1c &gt; 7%) and fasting plasma glucose &gt; 126 mg/dL.&#xD;
&#xD;
          -  Known history of human immunodeficiency virus infection or active infection with&#xD;
             hepatitis C virus or hepatitis B virus.&#xD;
&#xD;
          -  Concurrent chronic immunosuppressive treatment either with steroids or other&#xD;
             immunosuppressive agents.&#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>Josep Tabernero, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Vall d' Hebron Institute of Oncology (VHIO), Barcelona, Spain</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oncology Institute of Hope and Innovation</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Health System Institute for Research and Innovation</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO - Site Paul Papin</name>
      <address>
        <city>Angers</city>
        <zip>49055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO - Site René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <zip>44800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin</name>
      <address>
        <city>Berlin</city>
        <zip>12203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Carl Gustav Carus TU Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universitaet Muenchen Campus Grosshadern</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Munich</name>
      <address>
        <city>Munich</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Tuebingen</name>
      <address>
        <city>Tuebingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria San Martino</name>
      <address>
        <city>Genoa</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia (IEO)</name>
      <address>
        <city>Milan</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale Niguarda</name>
      <address>
        <city>Milan</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam University Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud Nijmegen</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Medisch Centrum</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Examen sp. z o.o.</name>
      <address>
        <city>Skórzewo</city>
        <zip>60-185</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii-Instytut im.M.Sklodowskiej Curie</name>
      <address>
        <city>Warsaw</city>
        <zip>00-001</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Colorectal Cancer</keyword>
  <keyword>PI3K Inhibitor</keyword>
  <keyword>PIK3CA mutated</keyword>
  <keyword>MEN1611</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>anti-EGFR</keyword>
  <keyword>mCRC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</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/NCT04495621
org study id: MEN1611-02
secondary id: 2019-003727-38
nct id: NCT04495621
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Open-label, dose-confirmation and cohort expansion, multicentre, Phase Ib/II study to assess
      the anti-tumour activity and safety of MEN1611 in combination with cetuximab for the
      treatment of patients with PIK3CA mutated metastatic colorectal cancer.
This Phase Ib/II study will investigate the anti-tumour activity and safety of daily oral
      doses MEN1611 in combination with cetuximab in female and male patients affected by PIK3CA
      mutated, N-K-RAS wild-type and BRAF wild-type metastatic colorectal cancer.

      MEN1611 is a potent, selective Class I phosphoinositide 3-kinase (PI3K) inhibitor. 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/II will start with a dose confirmation part (Step 1) to identify the RP2D of
      MEN1611 given in combination with cetuximab.

      The study will continue with a cohort expansion (Step 2) to explore the anti-tumour activity
      of the selected MEN1611 dose level combined with cetuximab with further assessment of their
      safety and tolerability.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of recommended phase II dose (RP2D)
time frame: 28 Days
description: Determination of the recommended phase II dose of MEN1611 when administered orally in combination with cetuximab to patients with PIK3CA mutated colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.
measure: Best overall response rate (ORR) according to RECIST v.1.1
time frame: 36 Months
description: Assessment of the anti-tumour activity of MEN1611 in combination with cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.
measure: Incidence of treatment emergent adverse events (TEAEs)
time frame: 36 Months
description: Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0.
arm group label: MEN1611
arm group type: Experimental
description: MEN1611 + Cetuximab
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: Cetuximab
description: Cetuximab solution for infusion administered weekly via IV infusion.
arm group label: MEN1611
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Josep Tabernero, MD PhD
role: Study Chair
affiliation: Vall d' Hebron Institute of Oncology (VHIO), Barcelona, Spain
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country: France
country: Germany
country: Italy
country: Netherlands
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Cetuximab