<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/NCT02975739</url>
  </required_header>
  <id_info>
    <org_study_id>NL54535.041.15</org_study_id>
    <nct_id>NCT02975739</nct_id>
  </id_info>
  <brief_title>Feasibility of Holmium-166 Micro Brachytherapy in Head and Neck Tumors</brief_title>
  <acronym>HIT</acronym>
  <official_title>Feasibility of Holmium-166 Microspheres for Selective Intra-tumoural Treatment in Head and Neck Cancer: Biodistribution and Safety in Patients With Malignancy of the Tongue</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective is to establish the feasibility of 166-Holmium microspheres for&#xD;
      intratumoral injections in oral squamous cell carcinoma (OSCC) of the tongue.&#xD;
&#xD;
      Participants will receive intratumoral injections with a low radioactive 166-Holmium&#xD;
      microspheres followed by surgical resection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      166-Holmium microspheres poly lactic acid microspheres are currently used in selective&#xD;
      internal radiation therapy. These microspheres emits beta radiation. The majority of the&#xD;
      radiation dose will be absorbed within 3.2 mm with a maximum penetration in tissue of 9 mm.&#xD;
      Therefore this can result in a high local tumor ablative dose with minimal dose to healthy&#xD;
      adjacent tissue.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow accrual&#xD;
  </why_stopped>
  <start_date>September 2016</start_date>
  <completion_date type="Actual">September 5, 2018</completion_date>
  <primary_completion_date type="Actual">September 5, 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>Total amount of activity leakage (in percentage) in the oral cavity rinsing fluid.</measure>
    <time_frame>upto 5 minutes after administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of (serious) adverse events</measure>
    <time_frame>Between administration and resection of the tumor (max 12 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The biodistribution of Holmium-166 microspheres after intra-tumoural injection</measure>
    <time_frame>upto 30 minutes after administration</time_frame>
    <description>SPECT Thorax and Abdomen Radioactivity in a blood and urine sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The biodistribution of Holmium-166 microspheres after intra-tumoural injection</measure>
    <time_frame>1-2 hours after administration</time_frame>
    <description>MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The biodistribution of Holmium-166 microspheres after intra-tumoural injection</measure>
    <time_frame>3 hours after administration</time_frame>
    <description>Radioactivity in blood and urine sample</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Radioisotopes</condition>
  <condition>Head and Neck Neoplasms</condition>
  <arm_group>
    <arm_group_label>Holmium-166 microspheres</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single session of 4 intratumoral injections consisting of 0.1-0.3 ml radioactive Holmium-166 microsphere suspension with a total activity 30 Megabecquerel, 7-12 days prior to surgical resection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Holmium-166 (poly L lactic acid) microspheres</intervention_name>
    <description>Intratumoral injections of Holmium-166 (poly L lactic acid) microspheres</description>
    <arm_group_label>Holmium-166 microspheres</arm_group_label>
    <other_name>Holmium microspheres</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have given written informed consent.&#xD;
&#xD;
          2. Aged 18 years and over.&#xD;
&#xD;
          3. Confirmed histological diagnosis of squamous cell carcinoma of the tongue.&#xD;
&#xD;
          4. primary tumor, regional nodes, metastasis (TNM) stage T1-2 Nx M0.&#xD;
&#xD;
          5. Eligible for local surgery with curative intent.&#xD;
&#xD;
          6. World Health Organization (WHO) Performance status 0-2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous oncologic surgery and/or external beam radiation therapy on the tongue and&#xD;
             oral floor.&#xD;
&#xD;
          2. Major surgery (Oro-facial) within the past 4 weeks or incompletely healed surgical&#xD;
             incisions before starting study therapy.&#xD;
&#xD;
          3. Any unresolved toxicity greater than National Cancer Institute (NCI), Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE version 4.03) grade 2 from previous&#xD;
             anti-cancer therapy.&#xD;
&#xD;
          4. Pregnancy or nursing (women of child-bearing potential).&#xD;
&#xD;
          5. Patients suffering from psychic disorders that make a comprehensive judgment&#xD;
             impossible, such as psychosis, hallucinations and/or depression.&#xD;
&#xD;
          6. Previous enrolment in the present study.&#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>Marnix G Lam, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMC Utrecht</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>van Es RJ, Nijsen JF, van het Schip AD, Dullens HF, Slootweg PJ, Koole R. Intra-arterial embolization of head-and-neck cancer with radioactive holmium-166 poly(L-lactic acid) microspheres: an experimental study in rabbits. Int J Oral Maxillofac Surg. 2001 Oct;30(5):407-13. doi: 10.1054/ijom.2001.0129.</citation>
    <PMID>11720043</PMID>
  </reference>
  <reference>
    <citation>Bult W, Vente MA, Vandermeulen E, Gielen I, Seevinck PR, Saunders J, van Het Schip AD, Bakker CJ, Krijger GC, Peremans K, Nijsen JF. Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study in a spontaneous cancer animal model. Brachytherapy. 2013 Mar-Apr;12(2):171-7. doi: 10.1016/j.brachy.2012.08.001. Epub 2012 Sep 19.</citation>
    <PMID>22999975</PMID>
  </reference>
  <reference>
    <citation>Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Mali WP, van Het Schip AD, Zonnenberg BA. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012 Oct;13(10):1025-34. doi: 10.1016/S1470-2045(12)70334-0. Epub 2012 Aug 22. Erratum In: Lancet Oncol. 2012 Nov;13(11):e464.</citation>
    <PMID>22920685</PMID>
  </reference>
  <reference>
    <citation>Bult W, de Leeuw H, Steinebach OM, van der Bom MJ, Wolterbeek HT, Heeren RM, Bakker CJ, van Het Schip AD, Hennink WE, Nijsen JF. Radioactive holmium acetylacetonate microspheres for interstitial microbrachytherapy: an in vitro and in vivo stability study. Pharm Res. 2012 Mar;29(3):827-36. doi: 10.1007/s11095-011-0610-7. Epub 2011 Nov 9.</citation>
    <PMID>22068276</PMID>
  </reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>September 5, 2018</last_update_submitted>
  <last_update_submitted_qc>September 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UMC Utrecht</investigator_affiliation>
    <investigator_full_name>Marnix Lam</investigator_full_name>
    <investigator_title>Professor Nuclear medicine</investigator_title>
  </responsible_party>
  <keyword>Intratumoral</keyword>
  <keyword>Tongue</keyword>
  <keyword>Microspheres</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02975739
org study id: NL54535.041.15
nct id: NCT02975739
lead sponsor: 
has dmc: Yes
The main objective is to establish the feasibility of 166-Holmium microspheres for
      intratumoral injections in oral squamous cell carcinoma (OSCC) of the tongue.

      Participants will receive intratumoral injections with a low radioactive 166-Holmium
      microspheres followed by surgical resection
166-Holmium microspheres poly lactic acid microspheres are currently used in selective
      internal radiation therapy. These microspheres emits beta radiation. The majority of the
      radiation dose will be absorbed within 3.2 mm with a maximum penetration in tissue of 9 mm.
      Therefore this can result in a high local tumor ablative dose with minimal dose to healthy
      adjacent tissue.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total amount of activity leakage (in percentage) in the oral cavity rinsing fluid.
time frame: upto 5 minutes after administration
measure: Occurrence of (serious) adverse events
time frame: Between administration and resection of the tumor (max 12 days)
measure: The biodistribution of Holmium-166 microspheres after intra-tumoural injection
time frame: upto 30 minutes after administration
description: SPECT Thorax and Abdomen Radioactivity in a blood and urine sample
measure: The biodistribution of Holmium-166 microspheres after intra-tumoural injection
time frame: 1-2 hours after administration
description: MRI
measure: The biodistribution of Holmium-166 microspheres after intra-tumoural injection
time frame: 3 hours after administration
description: Radioactivity in blood and urine sample
arm group label: Holmium-166 microspheres
arm group type: Experimental
description: Single session of 4 intratumoral injections consisting of 0.1-0.3 ml radioactive Holmium-166 microsphere suspension with a total activity 30 Megabecquerel, 7-12 days prior to surgical resection.
intervention type: Device
intervention name: Holmium-166 (poly L lactic acid) microspheres
description: Intratumoral injections of Holmium-166 (poly L lactic acid) microspheres
arm group label: Holmium-166 microspheres
other name: Holmium microspheres
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marnix G Lam, MD, PhD
role: Principal Investigator
affiliation: UMC Utrecht
facility: 
country: Netherlands
citation: van Es RJ, Nijsen JF, van het Schip AD, Dullens HF, Slootweg PJ, Koole R. Intra-arterial embolization of head-and-neck cancer with radioactive holmium-166 poly(L-lactic acid) microspheres: an experimental study in rabbits. Int J Oral Maxillofac Surg. 2001 Oct;30(5):407-13. doi: 10.1054/ijom.2001.0129.
PMID: 11720043
citation: Bult W, Vente MA, Vandermeulen E, Gielen I, Seevinck PR, Saunders J, van Het Schip AD, Bakker CJ, Krijger GC, Peremans K, Nijsen JF. Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study in a spontaneous cancer animal model. Brachytherapy. 2013 Mar-Apr;12(2):171-7. doi: 10.1016/j.brachy.2012.08.001. Epub 2012 Sep 19.
PMID: 22999975
citation: Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Mali WP, van Het Schip AD, Zonnenberg BA. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012 Oct;13(10):1025-34. doi: 10.1016/S1470-2045(12)70334-0. Epub 2012 Aug 22. Erratum In: Lancet Oncol. 2012 Nov;13(11):e464.
PMID: 22920685
citation: Bult W, de Leeuw H, Steinebach OM, van der Bom MJ, Wolterbeek HT, Heeren RM, Bakker CJ, van Het Schip AD, Hennink WE, Nijsen JF. Radioactive holmium acetylacetonate microspheres for interstitial microbrachytherapy: an in vitro and in vivo stability study. Pharm Res. 2012 Mar;29(3):827-36. doi: 10.1007/s11095-011-0610-7. Epub 2011 Nov 9.
PMID: 22068276
responsible party type: Principal Investigator
investigator affiliation: UMC Utrecht
investigator full name: Marnix Lam
investigator title: Professor Nuclear medicine
mesh term: Head and Neck Neoplasms
sharing ipd: Undecided