xml: <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/NCT05965817</url>
    </required_header>
    <id_info>
      <org_study_id>P23</org_study_id>
      <nct_id>NCT05965817</nct_id>
    </id_info>
    <brief_title>Fluorescence-guided Resection Of Colorectal Liver Metastases Using SGM-101 and Indocyanine GREEN</brief_title>
    <acronym>FOCUS GREEN</acronym>
    <official_title>Fluorescence-guided Resection Of Colorectal Liver Metastases Using SGM-101 and Indocyanine GREEN</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Leiden University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Leiden University Medical Center</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This will be the first trial testing the feasibility of working simultaneously with the two&#xD;
        fluorescent dyes ICG and SGM-101 in 10 patients with colorectal metastases.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        25-30% of patients with colorectal cancer develop colorectal liver metastases (CRLM).&#xD;
        Cornerstone for optimal survival is achieving radical surgical resections of all metastases .&#xD;
        To asisst the surgeon in achieving this, the use of intra-operative ICG for fluorescent&#xD;
        tumour delineation has widely been adopted as standard of care. Multiple international trials&#xD;
        have demonstrated that the use of ICG increases the rate of radical resections and result in&#xD;
        the detection of additional malignant lesions invisible to the naked eye. However, the rate&#xD;
        of false positives is still high and although it has increased the number of radical&#xD;
        resections, even in a minimal invasive cohort the unintended R1 rate is still as much as 8%.&#xD;
        Therefore, we are in need of an additional real-time intra-operative tool to detect R1&#xD;
        resections, especially in patients with a priori high risk for R1. To illustrate, in a large&#xD;
        shared database of the Erasmus University Medical Center we found that patients that either&#xD;
        received neoadjuvant chemotherapy, underwent a resection for &gt;3 CRLM or patients that had a&#xD;
        locally recurrent liver metastasis were independently associated with high R1 rates, ranging&#xD;
        between 23-29%. Therefore, we propose the addition of SGM-101, a tumour targeted&#xD;
        (carcinoembryonic antigen, CEA) NIR-fluorescence probe to ICG in patients scheduled for a&#xD;
        resection with high risk of R1, ultimately to reduce the R1 ratio. This is the first trial&#xD;
        testing the feasibility of working simultaneously with the two fluorescent dyes. If&#xD;
        feasibility is met in this trial, this is a step-up towards a powered trial with primary&#xD;
        objective to reduce the rate of R1 resections.&#xD;
  &#xD;
        An additional exploratory objective of this study is to investigate the feasibility of&#xD;
        SGM-101's potential to isolate circulating tumour cells (CTCs) and tumour-derived&#xD;
        extracellular vesicles (EVs) as biomarkers for CRC. The load of CTCs and EVs in the&#xD;
        circulation is strongly associated with poor clinical outcomes. Studies have shown that they&#xD;
        contain information about the molecular profile of the tumour. The administration of SGM-101&#xD;
        may enable the detection of CEA positive CTCs and EVs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 1, 2025</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>
      <intervention_model_description>In total 10 patients will be included who are scheduled for resection of colorectal liver metastases and meet at least one of the following criteria:&#xD;
  Scheduled for resection of &gt;3 CRLM or,&#xD;
  Completed neo-adjuvant chemotherapy, of which the last course was completed within 3 months before surgery or,&#xD;
  Scheduled for surgery because of a locally recurrent liver metastasis.</intervention_model_description>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the feasibility of simultaneous use of ICG and SGM-101 for intraoperative imaging of colorectal liver metastases.</measure>
      <time_frame>1.5 years</time_frame>
      <description>It is deemed feasible when it meets all of the following criteria:&#xD;
  A positive score on practical workability measured with survey A 'practical workability during surgery'&#xD;
  A positive score on the patient's experience measured with survey B 'patient experience'.&#xD;
  SGM-101: at least 80% sensitivity, measured as follows:&#xD;
  For capsular lesions, that are visible in white light are counted positive if TBR ≥ 1.5 in vivo.&#xD;
  For subcapsular lesions that are not visible in white light will be counted as positive if:&#xD;
  A: TBR ≥ 1.5 in vivo, OR B: TBR ≥ 1.5 ex vivo on whole specimen or on bread loafs&#xD;
  No cross-interference of fluorescent signal of both dyes within the two different excitation and emission channels.&#xD;
  Feasibility is reached when we get a positive result on all four items.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Colorectal Cancer</condition>
    <condition>Liver Metastasis Colon Cancer</condition>
    <condition>Image</condition>
    <arm_group>
      <arm_group_label>Patients with colorectal livermetastases receiving SGM-101 and ICG</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In total 10 patients will be included who are scheduled for resection of colorectal liver metastases and receive SGM-101 and ICG</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SGM-101 op top of ICG</intervention_name>
      <description>SGM-101 op top of ICG</description>
      <arm_group_label>Patients with colorectal livermetastases receiving SGM-101 and ICG</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  In order to be eligible to participate in this study, a subject must meet all of the&#xD;
               following criteria:&#xD;
  &#xD;
                 1. Diagnosed with liver metastases of colorectal origin for which surgical resection&#xD;
                    is proposed and meet at least one of the following criteria:&#xD;
  &#xD;
                      1. Scheduled for surgical resection of &gt;3 CRLM or;&#xD;
  &#xD;
                      2. completed neo-adjuvant therapy, of which the last course was completed&#xD;
                         within 3 months before surgery or;&#xD;
  &#xD;
                      3. Scheduled for surgery because of a locally recurrent liver metastasis.&#xD;
  &#xD;
                 2. ≥18 years old.&#xD;
  &#xD;
                 3. Willing and capable to give informed consent before study specific procedures&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  A potential subject who meets any of the following criteria will be excluded from&#xD;
               participation in this study:&#xD;
  &#xD;
                 1. Patients with contraindications for SGM-101&#xD;
  &#xD;
                      1. History of any anaphylactic shock;&#xD;
  &#xD;
                      2. Patients pregnant or breastfeeding (pregnancy should be ruled out by a&#xD;
                         pregnancy test within two weeks prior to administration of the conjugate);&#xD;
  &#xD;
                      3. Known positive test for human immunodeficiency virus (HIV), hepatitis B&#xD;
                         surface antigen (HBsAG) or hepatitis C virus (HCV) antibody or patients with&#xD;
                         untreated serious infections;&#xD;
  &#xD;
                      4. Previous administration of SGM-101&#xD;
  &#xD;
                 2. Patients with contraindications for Indocyanine green:&#xD;
  &#xD;
                      1. Allergy for shells and/or clamps&#xD;
  &#xD;
                      2. Hyperthyroidism&#xD;
  &#xD;
                      3. Known allergy for ICG&#xD;
  &#xD;
                 3. Any condition that the investigator considers to be potentially jeopardizing the&#xD;
                    patient's well-being or the study objectives&#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_contact>
      <last_name>Mats Warmerdam, Msc</last_name>
      <phone>0715298420</phone>
      <email>m.i.warmerdam@lumc.nl</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
      <investigator_full_name>Alexander Vahrmeijer</investigator_full_name>
      <investigator_title>Dr. A.L. Vahrmeijer</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasm Metastasis</mesh_term>
      <mesh_term>Liver Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Data will be coded and available only to the researchers of the LUMC on this particular trial. No other people will get access to the data. Results will be published.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965817
  org study id: P23
  nct id: NCT05965817
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This will be the first trial testing the feasibility of working simultaneously with the two
        fluorescent dyes ICG and SGM-101 in 10 patients with colorectal metastases.
  25-30% of patients with colorectal cancer develop colorectal liver metastases (CRLM).
        Cornerstone for optimal survival is achieving radical surgical resections of all metastases .
        To asisst the surgeon in achieving this, the use of intra-operative ICG for fluorescent
        tumour delineation has widely been adopted as standard of care. Multiple international trials
        have demonstrated that the use of ICG increases the rate of radical resections and result in
        the detection of additional malignant lesions invisible to the naked eye. However, the rate
        of false positives is still high and although it has increased the number of radical
        resections, even in a minimal invasive cohort the unintended R1 rate is still as much as 8%.
        Therefore, we are in need of an additional real-time intra-operative tool to detect R1
        resections, especially in patients with a priori high risk for R1. To illustrate, in a large
        shared database of the Erasmus University Medical Center we found that patients that either
        received neoadjuvant chemotherapy, underwent a resection for >3 CRLM or patients that had a
        locally recurrent liver metastasis were independently associated with high R1 rates, ranging
        between 23-29%. Therefore, we propose the addition of SGM-101, a tumour targeted
        (carcinoembryonic antigen, CEA) NIR-fluorescence probe to ICG in patients scheduled for a
        resection with high risk of R1, ultimately to reduce the R1 ratio. This is the first trial
        testing the feasibility of working simultaneously with the two fluorescent dyes. If
        feasibility is met in this trial, this is a step-up towards a powered trial with primary
        objective to reduce the rate of R1 resections.
  
        An additional exploratory objective of this study is to investigate the feasibility of
        SGM-101's potential to isolate circulating tumour cells (CTCs) and tumour-derived
        extracellular vesicles (EVs) as biomarkers for CRC. The load of CTCs and EVs in the
        circulation is strongly associated with poor clinical outcomes. Studies have shown that they
        contain information about the molecular profile of the tumour. The administration of SGM-101
        may enable the detection of CEA positive CTCs and EVs.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: In total 10 patients will be included who are scheduled for resection of colorectal liver metastases and meet at least one of the following criteria:
  Scheduled for resection of >3 CRLM or,
  Completed neo-adjuvant chemotherapy, of which the last course was completed within 3 months before surgery or,
  Scheduled for surgery because of a locally recurrent liver metastasis.
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: To assess the feasibility of simultaneous use of ICG and SGM-101 for intraoperative imaging of colorectal liver metastases.
  time frame: 1.5 years
  description: It is deemed feasible when it meets all of the following criteria:
  A positive score on practical workability measured with survey A 'practical workability during surgery'
  A positive score on the patient's experience measured with survey B 'patient experience'.
  SGM-101: at least 80% sensitivity, measured as follows:
  For capsular lesions, that are visible in white light are counted positive if TBR ≥ 1.5 in vivo.
  For subcapsular lesions that are not visible in white light will be counted as positive if:
  A: TBR ≥ 1.5 in vivo, OR B: TBR ≥ 1.5 ex vivo on whole specimen or on bread loafs
  No cross-interference of fluorescent signal of both dyes within the two different excitation and emission channels.
  Feasibility is reached when we get a positive result on all four items.
  arm group label: Patients with colorectal livermetastases receiving SGM-101 and ICG
  arm group type: Experimental
  description: In total 10 patients will be included who are scheduled for resection of colorectal liver metastases and receive SGM-101 and ICG
  intervention type: Drug
  intervention name: SGM-101 op top of ICG
  description: SGM-101 op top of ICG
  arm group label: Patients with colorectal livermetastases receiving SGM-101 and ICG
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Mats Warmerdam, Msc
  phone: 0715298420
  email: m.i.warmerdam@lumc.nl
  responsible party type: Principal Investigator
  investigator affiliation: Leiden University Medical Center
  investigator full name: Alexander Vahrmeijer
  investigator title: Dr. A.L. Vahrmeijer
  mesh term: Neoplasm Metastasis
  mesh term: Liver Neoplasms
  sharing ipd: No
  ipd description: Data will be coded and available only to the researchers of the LUMC on this particular trial. No other people will get access to the data. Results will be published.