<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/NCT03264716</url>
  </required_header>
  <id_info>
    <org_study_id>201701124DIPB</org_study_id>
    <nct_id>NCT03264716</nct_id>
  </id_info>
  <brief_title>Transarterial Chemoembolization by Hepasphere Microspheres for the Treatment of Unresectable Colorectal Liver Metastasis</brief_title>
  <official_title>A Prospective Open-label Study of Transarterial Chemoembolization by Hepasphere Microspheres for the Treatment of Unresectable Colorectal Liver Metastasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Colorectal cancer is the third most frequently diagnosed cancer and the third leading cause&#xD;
      of cancer related deaths in Taiwan. Of the 10,248 new colorectal patients diagnosed each year&#xD;
      approximately 60% will develop liver metastasis during the course of their disease. In&#xD;
      approximately 30% of these patients who develop liver metastasis the metastatic disease will&#xD;
      remain confined to the liver.&#xD;
&#xD;
      For the 70-75% of colorectal patients with colorectal liver metastasis not suitable for&#xD;
      hepatic resection or similarly ablative therapy with curative intent, systemic chemotherapy&#xD;
      is the standard initial management. However, after a patient has failed first- line and in&#xD;
      some cases second-line chemotherapy, response rates fall to as low as 12% (Chen HX 2006).&#xD;
      Transarterial chemoembolization (TACE) with microsphere is an alternative treatment because&#xD;
      normal liver tissue receives most of its blood supply from the portal vein, while colorectal&#xD;
      liver metastases derive most of their flow from the hepatic artery. Several clinical trials&#xD;
      have explored the feasibility and the efficacy of TACE with microsphere as a treatment for&#xD;
      patients with colorectal liver metastasis. HepaSphere represents a novel drug delivery system&#xD;
      for chemoembolization, which can add two benefits to embolization therapy. First, by&#xD;
      ionically binding the doxorubicin throughout the microspheres, more drug can be delivered&#xD;
      into the tumor, with less escape into peripheral circulation. Second, conformability to the&#xD;
      architecture of the vessel lumen, providing more contact surface area with the embolic&#xD;
      material and the vessel intima, leading to a more complete occlusion. However, there are&#xD;
      limited experiences in using HepaSphere TACE for colorectal liver metastasis in Taiwan. In&#xD;
      this pilot study, we will evaluate the initiate safety and efficacy of Hepasphere&#xD;
      microspheres loaded with a chemotherapeutic agent doxorubicin for the treatment of patients&#xD;
      who have failed first-line and second-line systemic chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, non-comparative study aimed to evaluate the safety profiles and&#xD;
      efficacy of patients with unresectable colorectal liver metastases treated by selective TACE&#xD;
      (transarterial chemoembolization) using HepaSphere load with doxorubicin. Total of 15&#xD;
      patients will be planned to recruit.&#xD;
&#xD;
      The study procedures will consist of a screening period in which patient eligibility will be&#xD;
      determined. Patients meeting the study entry criteria will receive one HepaSphere treatments.&#xD;
      Computed tomography (CT) will be done 4 weeks after treatment to determine tumor response.&#xD;
&#xD;
      Hepatic progression free survival will be followed from the date of first study HepaSphere&#xD;
      procedure until a date of target liver tumor progression is obtained or the patient is lost&#xD;
      to follow-up. Treatments for liver metastases after the study HepaSphere treatments are&#xD;
      complete will be documented during the survival period to the extent possible.&#xD;
&#xD;
      The investigators will evaluate subjects' previous treatments and response, and determine to&#xD;
      use doxorubicin for subjects. 100 mg doxorubicin will be loaded onto the HepaSphere&#xD;
      Microspheres (through ionic bonding when the spheres are exposed to doxorubicin solubilized&#xD;
      in non-ionic contrast medium) and delivered via microcatheter. No ethiodized oil is used with&#xD;
      the microspheres. The occlusion endpoint will be stasis to the second or third branches. If&#xD;
      stasis has not been reached when the target dosage of doxorubicin has been delivered,&#xD;
      additional bland embolic agent will be used to achieve a consistent endpoint. Other&#xD;
      concurrent chemotherapy, such as Xeloda, 5-fluorouracil but not limited, can be used in&#xD;
      combination with HepaSphere Tx.&#xD;
&#xD;
      The study will evaluate safety throughout the protocol specified treatment phase of the&#xD;
      investigation by assessing adverse events, as well as changes from baseline in laboratory&#xD;
      values, findings on physical examination including vital signs and Eastern Cooperative&#xD;
      Oncology Group (ECOG) performance status. Concomitant medication usage will also be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Actual">September 11, 2018</completion_date>
  <primary_completion_date type="Actual">January 26, 2018</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hepatic Progression free survival</measure>
    <time_frame>up to one year</time_frame>
    <description>To define all participants from the day of the first HepaSphere Tx until the date that hepatic progression or death is first reported, whichever comes first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>An overall tumor response classification</measure>
    <time_frame>up to one year</time_frame>
    <description>The tumor response will be assessed using modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria to evaluate tumor necrosis, and includes assessment of viable tumor, which is defined as uptake of contrast agent in the arterial phase of computed tomography (CT).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Unresectable Colorectal Liver Metastasis</condition>
  <arm_group>
    <arm_group_label>HepaSphere TACE (transarterial chemoembolization)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Using HepaSphere TACE (transarterial chemoembolization) for colorectal liver metastasis. TACE using HepaSphere load with doxorubicin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>HepaSphere TACE (transarterial chemoembolization)</intervention_name>
    <description>100 mg doxorubicin will be loaded onto the HepaSphere Microspheres and delivered via microcatheter.</description>
    <arm_group_label>HepaSphere TACE (transarterial chemoembolization)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must meet all of the following inclusion criteria in order to be entered into&#xD;
             the study:&#xD;
&#xD;
               1. Liver dominant metastatic colorectal cancer&#xD;
&#xD;
               2. Metastatic colorectal patients who have failed first-line and second-line&#xD;
                  systemic chemotherapy.&#xD;
&#xD;
               3. ECOG 0 to 1 or a Karnofsky Performance score of 80-100%;&#xD;
&#xD;
               4. Age 20 years or older&#xD;
&#xD;
               5. Patient has signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - If patients meet any of the following criteria they may not be entered into the study:&#xD;
&#xD;
          1. History of severe allergy or intolerance to any contrast media not controlled with&#xD;
             premedication&#xD;
&#xD;
          2. Severe peripheral vascular disease that would preclude catheterization&#xD;
&#xD;
          3. Significant extra-hepatic disease, generally in excess of 50% of the overall whole&#xD;
             body tumor bulk outside the liver, or any tumor burden that represented an imminent&#xD;
             threat to the patient's life&#xD;
&#xD;
          4. Greater than 75% hepatic parenchymal involvement. Previous treatment with any form of&#xD;
             transarterial embolization for liver tumors&#xD;
&#xD;
        f. Female patients who are pregnant, breastfeeding, or premenopausal and not using an&#xD;
        effective method of contraceptive g. Any contraindication to arteriography or hepatic&#xD;
        embolization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kai-Wen Huang, MD. PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>May 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>July 11, 2019</last_update_submitted>
  <last_update_submitted_qc>July 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TACE (transarterial chemoembolization)</keyword>
  <keyword>colorectal liver metastasis</keyword>
  <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>
  </patient_data>
  <!-- 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/NCT03264716
org study id: 201701124DIPB
nct id: NCT03264716
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Colorectal cancer is the third most frequently diagnosed cancer and the third leading cause
      of cancer related deaths in Taiwan. Of the 10,248 new colorectal patients diagnosed each year
      approximately 60% will develop liver metastasis during the course of their disease. In
      approximately 30% of these patients who develop liver metastasis the metastatic disease will
      remain confined to the liver.

      For the 70-75% of colorectal patients with colorectal liver metastasis not suitable for
      hepatic resection or similarly ablative therapy with curative intent, systemic chemotherapy
      is the standard initial management. However, after a patient has failed first- line and in
      some cases second-line chemotherapy, response rates fall to as low as 12% (Chen HX 2006).
      Transarterial chemoembolization (TACE) with microsphere is an alternative treatment because
      normal liver tissue receives most of its blood supply from the portal vein, while colorectal
      liver metastases derive most of their flow from the hepatic artery. Several clinical trials
      have explored the feasibility and the efficacy of TACE with microsphere as a treatment for
      patients with colorectal liver metastasis. HepaSphere represents a novel drug delivery system
      for chemoembolization, which can add two benefits to embolization therapy. First, by
      ionically binding the doxorubicin throughout the microspheres, more drug can be delivered
      into the tumor, with less escape into peripheral circulation. Second, conformability to the
      architecture of the vessel lumen, providing more contact surface area with the embolic
      material and the vessel intima, leading to a more complete occlusion. However, there are
      limited experiences in using HepaSphere TACE for colorectal liver metastasis in Taiwan. In
      this pilot study, we will evaluate the initiate safety and efficacy of Hepasphere
      microspheres loaded with a chemotherapeutic agent doxorubicin for the treatment of patients
      who have failed first-line and second-line systemic chemotherapy.
This is an open-label, non-comparative study aimed to evaluate the safety profiles and
      efficacy of patients with unresectable colorectal liver metastases treated by selective TACE
      (transarterial chemoembolization) using HepaSphere load with doxorubicin. Total of 15
      patients will be planned to recruit.

      The study procedures will consist of a screening period in which patient eligibility will be
      determined. Patients meeting the study entry criteria will receive one HepaSphere treatments.
      Computed tomography (CT) will be done 4 weeks after treatment to determine tumor response.

      Hepatic progression free survival will be followed from the date of first study HepaSphere
      procedure until a date of target liver tumor progression is obtained or the patient is lost
      to follow-up. Treatments for liver metastases after the study HepaSphere treatments are
      complete will be documented during the survival period to the extent possible.

      The investigators will evaluate subjects' previous treatments and response, and determine to
      use doxorubicin for subjects. 100 mg doxorubicin will be loaded onto the HepaSphere
      Microspheres (through ionic bonding when the spheres are exposed to doxorubicin solubilized
      in non-ionic contrast medium) and delivered via microcatheter. No ethiodized oil is used with
      the microspheres. The occlusion endpoint will be stasis to the second or third branches. If
      stasis has not been reached when the target dosage of doxorubicin has been delivered,
      additional bland embolic agent will be used to achieve a consistent endpoint. Other
      concurrent chemotherapy, such as Xeloda, 5-fluorouracil but not limited, can be used in
      combination with HepaSphere Tx.

      The study will evaluate safety throughout the protocol specified treatment phase of the
      investigation by assessing adverse events, as well as changes from baseline in laboratory
      values, findings on physical examination including vital signs and Eastern Cooperative
      Oncology Group (ECOG) performance status. Concomitant medication usage will also be assessed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hepatic Progression free survival
time frame: up to one year
description: To define all participants from the day of the first HepaSphere Tx until the date that hepatic progression or death is first reported, whichever comes first.
measure: An overall tumor response classification
time frame: up to one year
description: The tumor response will be assessed using modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria to evaluate tumor necrosis, and includes assessment of viable tumor, which is defined as uptake of contrast agent in the arterial phase of computed tomography (CT).
arm group label: HepaSphere TACE (transarterial chemoembolization)
arm group type: Experimental
description: Using HepaSphere TACE (transarterial chemoembolization) for colorectal liver metastasis. TACE using HepaSphere load with doxorubicin.
intervention type: Device
intervention name: HepaSphere TACE (transarterial chemoembolization)
description: 100 mg doxorubicin will be loaded onto the HepaSphere Microspheres and delivered via microcatheter.
arm group label: HepaSphere TACE (transarterial chemoembolization)
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Kai-Wen Huang, MD. PhD.
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Liver Neoplasms
sharing ipd: No