<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/NCT02208804</url>
  </required_header>
  <id_info>
    <org_study_id>14-287/D</org_study_id>
    <nct_id>NCT02208804</nct_id>
  </id_info>
  <brief_title>Surefire Infusion System vs. Standard Microcatheter Use During Holmium-166 Radioembolization</brief_title>
  <acronym>SIM</acronym>
  <official_title>Surefire Infusion System vs. Standard Microcatheter Use During Holmium-166 Radioembolization for the Treatment of Colorectal Liver Metastases (SIM Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UMC Utrecht</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the SIM trial is to investigate whether using the Surefire Infusion System&#xD;
      during holmium-166 radioembolization increases the posttreatment tumor to non-tumor activity&#xD;
      concentration ratio, compared with using a standard end-hole microcatheter.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design: clinical within-subject randomized controlled trial.&#xD;
&#xD;
      Study population: 25 patients with unresectable, chemorefractory, liver-dominant colorectal&#xD;
      liver metastases.&#xD;
&#xD;
      Intervention: scout and therapeutic doses of holmium-166 microspheres will be administered in&#xD;
      the left and right hepatic artery during two sequential angiography procedures on the same&#xD;
      day. In all subjects, the use of the Surefire Infusion System and the standard end-hole&#xD;
      catheter will be randomly allocated to the infusion site (left and right hepatic artery).&#xD;
&#xD;
      Baseline and follow-up investigation: at baseline and during follow-up, patients will undergo&#xD;
      physical examination and laboratory investigations for toxicity assessment, and a whole-body&#xD;
      18F-FDG-PET + dual-phase liver CT (at baseline and 3-months follow-up) for tumor response&#xD;
      assessment. After the scout procedure and therapeutic procedure, a holmium-166 SPECT/CT will&#xD;
      be obtained for the assessment of the microsphere distribution.&#xD;
&#xD;
      Main study parameters/endpoints:&#xD;
&#xD;
      The primary endpoint is the tumor to non-tumor activity concentration ratio on SPECT/CT.&#xD;
&#xD;
      Secondary endpoints include mean absorbed doses of radioactivity in tumorous and healthy&#xD;
      liver tissue, tumor response, the predictive value of holmium-166 scout dose and infusion&#xD;
      efficiency. These endpoints will be compared between the Surefire Infusion System and&#xD;
      standard microcatheter infusions. A dose-response relationship, clinical toxicity and overall&#xD;
      survival will be assessed for the entire cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <primary_completion_date type="Anticipated">November 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Posttreatment tumor to non-tumor activity concentration ratio on SPECT/CT</measure>
    <time_frame>5 days after treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean absorbed radiation doses in tumorous and healthy liver tissue on SPECT/CT</measure>
    <time_frame>5 days after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Posttreatment tumor response on CT and 18F-FDG-PET</measure>
    <time_frame>3 months after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive value of the holmium-166 scout dose</measure>
    <time_frame>On the day of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-response relationship between tumor absorbed doses on SPECT/CT and tumor response on CT and 18F-FDG-PET</measure>
    <time_frame>3 months after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infusion efficiency</measure>
    <time_frame>On the day of treatment</time_frame>
    <description>Defined as the percentage of calculated treatment activity that was administered</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of treatment until the date of death from any cause, assessed up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical and laboratory toxicity</measure>
    <time_frame>Up to 3 months after treatment</time_frame>
    <description>According to Common Terminology Criteria for Adverse Events version 4.03</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Colorectal Neoplasms</condition>
  <condition>Neoplasm Metastasis</condition>
  <condition>Liver Diseases</condition>
  <condition>Digestive System Neoplasms</condition>
  <arm_group>
    <arm_group_label>Surefire Infusion System</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hepatic arterial administrations using the Surefire Infusion System</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard End-hole Microcatheter</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hepatic arterial administrations using the standard end-hole microcatheter</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Holmium-166-poly (L-lactic acid) microspheres</intervention_name>
    <arm_group_label>Standard End-hole Microcatheter</arm_group_label>
    <arm_group_label>Surefire Infusion System</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Histopathologically confirmed diagnosis of adenocarcinoma of the colon or rectum&#xD;
&#xD;
          -  Hepatic metastases with measurable morphological appearance (≥ 1 cm) on cross&#xD;
             sectional imaging, located in the right and left hepatic arterial perfusion territory&#xD;
&#xD;
          -  Unresectable, liver dominant disease&#xD;
&#xD;
          -  Progressive disease after second line chemotherapy or no further chemotherapeutical&#xD;
             treatment options due to severe side effects or unwillingness of the patient to&#xD;
             undergo systemic chemotherapy&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Expected adequacy of follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  World health organization performance score &gt; 2&#xD;
&#xD;
          -  Inadequate bone marrow function (hemoglobin &lt; 6.0 mmol/l, leukocyte count &lt; 3.0 x&#xD;
             109/l, platelet count &lt; 75x 109/l), inadequate liver function (bilirubin &gt; 35 µmol/l,&#xD;
             aspartate aminotransferase / alanine aminotransferase (AST/ALT) &gt; 5 x upper limit of&#xD;
             normal (ULN)) or inadequate renal function (creatinine &gt; 1.5 x ULN)&#xD;
&#xD;
          -  Prior hemihepatectomy&#xD;
&#xD;
          -  Compromised biliary system (biliary stent or hepaticojejunostomy)&#xD;
&#xD;
          -  Child Pugh score B7 or worse&#xD;
&#xD;
          -  Active hepatitis B or C&#xD;
&#xD;
          -  Main portal vein thrombosis on CT (or previous portal vein embolization)&#xD;
&#xD;
          -  Severe celiac axis stenosis on CT&#xD;
&#xD;
          -  Unsuitable hepatic arterial anatomy on CT&#xD;
&#xD;
          -  Treatment with systemic chemotherapy within 4 weeks prior to radioembolization&#xD;
&#xD;
          -  Previous participation in a study classified as class III by a radiation safety&#xD;
             committee&#xD;
&#xD;
          -  Bleeding diathesis&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Life expectancy &lt; 3 months&#xD;
&#xD;
          -  Patients who are declared incompetent&#xD;
&#xD;
          -  Any condition that prevents from safe treatment with radioembolization&#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>Maurice AAJ van den Bosch, Prof. dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMCU Utrecht, The Netherlands</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Max A Viergever, Prof. dr. ir.</last_name>
    <role>Study Director</role>
    <affiliation>UMC Utrecht, The Netherlands</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maurice AAJ van den Bosch, Prof. dr.</last_name>
    <phone>+ 31 88 7554755</phone>
    <email>mbosch@umcutrecht.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Andor F van den Hoven, MD</last_name>
    <phone>+ 31 88 7567375</phone>
    <email>a.f.vandenhoven@umcutrecht.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Radiology and Nuclear Medicine, University Medical Center Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>November 7, 2016</last_update_submitted>
  <last_update_submitted_qc>November 7, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 9, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UMC Utrecht</investigator_affiliation>
    <investigator_full_name>Maurice A.A.J. van den Bosch</investigator_full_name>
    <investigator_title>Prof. dr.</investigator_title>
  </responsible_party>
  <keyword>Colorectal Cancer Liver Metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Digestive System Neoplasms</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Liver Diseases</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/NCT02208804
org study id: 14-287/D
nct id: NCT02208804
lead sponsor: 
has dmc: No
The objective of the SIM trial is to investigate whether using the Surefire Infusion System
      during holmium-166 radioembolization increases the posttreatment tumor to non-tumor activity
      concentration ratio, compared with using a standard end-hole microcatheter.
Study design: clinical within-subject randomized controlled trial.

      Study population: 25 patients with unresectable, chemorefractory, liver-dominant colorectal
      liver metastases.

      Intervention: scout and therapeutic doses of holmium-166 microspheres will be administered in
      the left and right hepatic artery during two sequential angiography procedures on the same
      day. In all subjects, the use of the Surefire Infusion System and the standard end-hole
      catheter will be randomly allocated to the infusion site (left and right hepatic artery).

      Baseline and follow-up investigation: at baseline and during follow-up, patients will undergo
      physical examination and laboratory investigations for toxicity assessment, and a whole-body
      18F-FDG-PET + dual-phase liver CT (at baseline and 3-months follow-up) for tumor response
      assessment. After the scout procedure and therapeutic procedure, a holmium-166 SPECT/CT will
      be obtained for the assessment of the microsphere distribution.

      Main study parameters/endpoints:

      The primary endpoint is the tumor to non-tumor activity concentration ratio on SPECT/CT.

      Secondary endpoints include mean absorbed doses of radioactivity in tumorous and healthy
      liver tissue, tumor response, the predictive value of holmium-166 scout dose and infusion
      efficiency. These endpoints will be compared between the Surefire Infusion System and
      standard microcatheter infusions. A dose-response relationship, clinical toxicity and overall
      survival will be assessed for the entire cohort.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Posttreatment tumor to non-tumor activity concentration ratio on SPECT/CT
time frame: 5 days after treatment
measure: Mean absorbed radiation doses in tumorous and healthy liver tissue on SPECT/CT
time frame: 5 days after treatment
measure: Posttreatment tumor response on CT and 18F-FDG-PET
time frame: 3 months after treatment
measure: Predictive value of the holmium-166 scout dose
time frame: On the day of treatment
measure: Dose-response relationship between tumor absorbed doses on SPECT/CT and tumor response on CT and 18F-FDG-PET
time frame: 3 months after treatment
measure: Infusion efficiency
time frame: On the day of treatment
description: Defined as the percentage of calculated treatment activity that was administered
measure: Overall survival
time frame: From date of treatment until the date of death from any cause, assessed up to 1 year
measure: Clinical and laboratory toxicity
time frame: Up to 3 months after treatment
description: According to Common Terminology Criteria for Adverse Events version 4.03
arm group label: Surefire Infusion System
arm group type: Experimental
description: Hepatic arterial administrations using the Surefire Infusion System
arm group label: Standard End-hole Microcatheter
arm group type: Active Comparator
description: Hepatic arterial administrations using the standard end-hole microcatheter
intervention type: Device
intervention name: Holmium-166-poly (L-lactic acid) microspheres
arm group label: Standard End-hole Microcatheter
arm group label: Surefire Infusion System
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maurice AAJ van den Bosch, Prof. dr.
role: Principal Investigator
affiliation: UMCU Utrecht, The Netherlands
last name: Max A Viergever, Prof. dr. ir.
role: Study Director
affiliation: UMC Utrecht, The Netherlands
last name: Maurice AAJ van den Bosch, Prof. dr.
phone: + 31 88 7554755
email: mbosch@umcutrecht.nl
last name: Andor F van den Hoven, MD
phone: + 31 88 7567375
email: a.f.vandenhoven@umcutrecht.nl
facility: 
status: Recruiting
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: UMC Utrecht
investigator full name: Maurice A.A.J. van den Bosch
investigator title: Prof. dr.
mesh term: Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Colorectal Neoplasms
mesh term: Digestive System Neoplasms
mesh term: Gastrointestinal Neoplasms
mesh term: Liver Diseases