<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/NCT03803241</url>
  </required_header>
  <id_info>
    <org_study_id>2014-001402-18</org_study_id>
    <nct_id>NCT03803241</nct_id>
  </id_info>
  <brief_title>Cd133+ Cell Infusion in Patients With Colorectal Liver Metastases.</brief_title>
  <acronym>cellcol</acronym>
  <official_title>Cd133+ Cell Infusion in Patients With Colorectal Liver Metastases That Are Going to be Submitted to a Major Liver Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital San Carlos, Madrid</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital San Carlos, Madrid</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>
      Treatment of patients with metastatic colorectal carcinoma is surgical resection. Only 10-15%&#xD;
      of the patients will be candidates for curative resection. After response to chemotherapy&#xD;
      this figure rises 10-13% more. To perform the surgery it is necessary to have a sufficient&#xD;
      remnant liver volume (RLV), which allows maintaining optimal liver function after resection.&#xD;
      If the estimated RLV is insufficient preoperatively, portal venous embolization site (PVE) is&#xD;
      performed for compensatory hypertrophy, thus increasing the number of resections 19%. Still,&#xD;
      in 20% of these patients surgery can not be performed because RLV is not achieved or because&#xD;
      the disease progresses while waiting for growth. Therefore, it is necessary to improve liver&#xD;
      regeneration without promoting tumor growth. Studies on liver regeneration, have determined&#xD;
      that cells (CD133 +) are involved in the liver hypertrophy that occurs after hepatectomy.&#xD;
      CD133 + have been used to induce liver hypertrophy with encouraging results. This population&#xD;
      of CD133 +, can be selected from peripheral blood after stimulation with Granulocyte&#xD;
      colony-stimulating factor (G-CSF), being able to obtain a large number of them. The&#xD;
      investigators propose to treat patients who do not meet criteria for surgery because of&#xD;
      insufficient volume &lt;40%, with CD133 + and portal embolization in order to carry out a&#xD;
      surgical resection in a second place.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 31, 2019</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver volume</measure>
    <time_frame>once residual liver volume reach &gt;40%, an average of 5 weeks.</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 30 days</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 90 days</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 180 days</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 12 months</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 18 months</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volume</measure>
    <time_frame>Post-surgery follow-up visits the first 24 months</time_frame>
    <description>Liver volume estimated by computed tomography</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>PVE + CD133</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>preop portal vein embolization + stem cells infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PVE</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>only preop portal vein embolization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CD133+ infusion</intervention_name>
    <description>Infusion of cells cd133+</description>
    <arm_group_label>PVE + CD133</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>portal vein embolization</intervention_name>
    <description>portal vein embolization</description>
    <arm_group_label>PVE</arm_group_label>
    <arm_group_label>PVE + CD133</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Men and women between ≥ 18 years and ≤ 80. Women in fertile age should use&#xD;
             contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG).&#xD;
&#xD;
          2. ECOG (Eastern Cooperative Oncology Group) quality of life scale ≤ 2.&#xD;
&#xD;
          3. Patients with hepatic metastases of colorectal carcinoma and insufficient hepatic&#xD;
             remnant function to perform a major hepatectomy. This volume would be calculated by&#xD;
             Positron emission tomography-Computed tomography (PET-CT) images or 64-channel&#xD;
             multidetector CT.&#xD;
&#xD;
             In patients who have received preoperative chemotherapy, the estimate residual liver&#xD;
             volume to be included in the study will be &lt;40%.&#xD;
&#xD;
             Patients who have preserved liver function (Child ≤ B7 and International Normalized&#xD;
             Ratio (INR) ≤ 2 in non-anticoagulated patients) and those who have not received&#xD;
             chemotherapy, needs &lt; 30% of residual volume to be included in the study.&#xD;
&#xD;
          4. Patients should have signed informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Pregnancy or lactation period.&#xD;
&#xD;
          2. Any condition that the investigators consider an unjustifiable risk in the patient.&#xD;
&#xD;
          3. Severe comorbidities: American Society of Anesthesiologists (ASA) ≥ 4.&#xD;
&#xD;
          4. Alterations in the hemogram and morphological alterations, evaluated by hematologist&#xD;
             prior to administration of G-CSF.&#xD;
&#xD;
          5. Liver function: Child ≥ B7 and INR ≥ 2 in non-anticoagulated patients. In&#xD;
             anticoagulated patients the values will have to be reverse, prior to surgery.&#xD;
&#xD;
          6. Patients who have not received research drugs in the last 30 days or in the period of&#xD;
             5 elimination half-life.&#xD;
&#xD;
          7. In patients on chemotherapy treatment, G-CSF can not be administered until 48 hours&#xD;
             after the last administration of chemotherapy. Patients who have received Bevacizumab&#xD;
             must wait 30 days since the last administration.&#xD;
&#xD;
          8. In addition, all those aspects that prevent the patient from being part of the study,&#xD;
             understand the rules, follow the instructions given, or other aspects.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alejandra Garcia Botella</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>September 22, 2021</last_update_submitted>
  <last_update_submitted_qc>September 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital San Carlos, Madrid</investigator_affiliation>
    <investigator_full_name>Alejandra Garcia Botella</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_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/NCT03803241
org study id: 2014-001402-18
nct id: NCT03803241
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Treatment of patients with metastatic colorectal carcinoma is surgical resection. Only 10-15%
      of the patients will be candidates for curative resection. After response to chemotherapy
      this figure rises 10-13% more. To perform the surgery it is necessary to have a sufficient
      remnant liver volume (RLV), which allows maintaining optimal liver function after resection.
      If the estimated RLV is insufficient preoperatively, portal venous embolization site (PVE) is
      performed for compensatory hypertrophy, thus increasing the number of resections 19%. Still,
      in 20% of these patients surgery can not be performed because RLV is not achieved or because
      the disease progresses while waiting for growth. Therefore, it is necessary to improve liver
      regeneration without promoting tumor growth. Studies on liver regeneration, have determined
      that cells (CD133 +) are involved in the liver hypertrophy that occurs after hepatectomy.
      CD133 + have been used to induce liver hypertrophy with encouraging results. This population
      of CD133 +, can be selected from peripheral blood after stimulation with Granulocyte
      colony-stimulating factor (G-CSF), being able to obtain a large number of them. The
      investigators propose to treat patients who do not meet criteria for surgery because of
      insufficient volume <40%, with CD133 + and portal embolization in order to carry out a
      surgical resection in a second place.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Liver volume
time frame: once residual liver volume reach >40%, an average of 5 weeks.
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 30 days
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 90 days
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 180 days
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 12 months
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 18 months
description: Liver volume estimated by computed tomography
measure: Liver volume
time frame: Post-surgery follow-up visits the first 24 months
description: Liver volume estimated by computed tomography
arm group label: PVE + CD133
arm group type: Experimental
description: preop portal vein embolization + stem cells infusion
arm group label: PVE
arm group type: Sham Comparator
description: only preop portal vein embolization
intervention type: Drug
intervention name: CD133+ infusion
description: Infusion of cells cd133+
arm group label: PVE + CD133
intervention type: Other
intervention name: portal vein embolization
description: portal vein embolization
arm group label: PVE
arm group label: PVE + CD133
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Hospital San Carlos, Madrid
investigator full name: Alejandra Garcia Botella
investigator title: Principal investigator
mesh term: Colorectal Neoplasms