<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/NCT02233387</url>
  </required_header>
  <id_info>
    <org_study_id>11-36-14/12</org_study_id>
    <nct_id>NCT02233387</nct_id>
  </id_info>
  <brief_title>PET CT With HX4 in Cervix Cancer</brief_title>
  <acronym>HX4-cervix</acronym>
  <official_title>Non Invasive Imaging of [18F]HX4 With Positron-Emission-Tomography (PET) in Cervix Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht Radiation Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht Radiation Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is:&#xD;
&#xD;
        1. to determine if tumor hypoxia can be accurately visualised with [18F]HX4 PET imaging in&#xD;
           cervix cancer,&#xD;
&#xD;
        2. to correlate the [18F]HX4 PET images with blood and tissue markers,&#xD;
&#xD;
        3. to investigate the quality and optimal timing of [18F]HX4 PET images,&#xD;
&#xD;
        4. to compare [18F]HX4 PET uptake with [18F]FDG PET uptake before and after treatment and&#xD;
&#xD;
        5. analyze correlation with responses&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tumor hypoxia is the situation where tumor cells are or have been deprived of oxygen. Hypoxic&#xD;
      tumor cells are usually more resistant to radiotherapy and chemotherapy and more likely to&#xD;
      develop metastasis. In Cervix cancer, tumor hypoxia is known to be an important prognostic&#xD;
      factor for long term survival. [18F]HX4 is being developed as a diagnostic&#xD;
      radiopharmaceutical for PET imaging to find a marker for hypoxia that can be used in standard&#xD;
      clinical practice. Current hypoxia tracers lack reliable image quality and kinetics. Because&#xD;
      of the short half life and clearance, the investigators expect that [18F]HX4 will have a&#xD;
      higher tumor to background ratio than current nitro-imidazole hypoxia markers such as&#xD;
      [18F]-misonidazole. In a recent phase 1 clinical study from van Loon et al, PET-imaging with&#xD;
      [18F]HX4 was feasible without any toxicity. The clinical use of a reliable, non-invasive and&#xD;
      easy to use hypoxia imaging agent could allow selection of patients most likely to benefit&#xD;
      from hypoxia modifying therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    patients did not want to participate&#xD;
  </why_stopped>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visualisation of tumor hypoxia with [18F] HX4 PET imaging</measure>
    <time_frame>2 year</time_frame>
    <description>Visualisation of tumor hypoxia with [18F] HX4 PET imaging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observation of spatial and temporal stability of [18F] HX4 PET images</measure>
    <time_frame>2 year</time_frame>
    <description>Observation of spatial and temporal stability of [18F] HX4 PET images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations with Complete Remission rates at 3 months restaging evaluation</measure>
    <time_frame>2 year</time_frame>
    <description>Correlations with Complete Remission rates at 3 months restaging evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Image quality of [18F] HX4-PET at different time points</measure>
    <time_frame>2 year</time_frame>
    <description>Image quality of [18F] HX4-PET at different time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic analysis of HX4</measure>
    <time_frame>2 year</time_frame>
    <description>Kinetic analysis of HX4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX)</measure>
    <time_frame>2 year</time_frame>
    <description>Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes</measure>
    <time_frame>2 year</time_frame>
    <description>Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment</measure>
    <time_frame>2 year</time_frame>
    <description>Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment</measure>
    <time_frame>2 year</time_frame>
    <description>Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Cervix Cancer</condition>
  <arm_group>
    <arm_group_label>[18F] HX4 PET imaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>injection with [18F] HX4 and PET imaging at baseline and after 20 Gy radiotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>injection with [18F] HX4 and PET imaging</intervention_name>
    <description>A standard clinical [18F]FDG PET-CT will be performed for the radiotherapy planning.&#xD;
After a minimum time interval of 24 hours, baseline [18F]HX4 PET scans will be performed:&#xD;
Based on the phase I trial1 444 MBq (12 mCi) [18F]HX4 is administrated via a bolus IV injection.&#xD;
The first image acquisition is started together with the administration of [18F]HX4 (30-40 min dynamic). Static scans are acquired at 90 min, 180 min and 240 min p.i</description>
    <arm_group_label>[18F] HX4 PET imaging</arm_group_label>
    <other_name>3-[18F]fluoro- 2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1- yl)propan-1-ol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Histologically confirmed cervix carcinoma (squamous cell carcinoma, adenocarcinoma or&#xD;
             adenosquamous carcinoma)&#xD;
&#xD;
          -  tumor stages FIGO IB - IVA&#xD;
&#xD;
          -  WHO performance status 0 to 2&#xD;
&#xD;
          -  Scheduled for primary curative radiotherapy (either or not combined with chemotherapy&#xD;
             or hyperthermia)&#xD;
&#xD;
          -  No previous surgery to the Cervix&#xD;
&#xD;
          -  No previous radiation to the Cervix&#xD;
&#xD;
          -  The patient is willing and capable to comply with study procedures&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Written informed consent before patient registration&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Recent (&lt; 3 months) myocardial infarction&#xD;
&#xD;
          -  Uncontrolled infectious disease&#xD;
&#xD;
          -  Pregnant or breast feeding and/or not willing to take adequate contraceptive measures&#xD;
             during the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Philippe Lambin, prof MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Maastro Clinic, The Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MAASTRO clinic</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 ET</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>February 29, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <last_update_submitted>March 7, 2019</last_update_submitted>
  <last_update_submitted_qc>March 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cervix cancer</keyword>
  <keyword>[18F] HX4 PET imaging</keyword>
  <keyword>hypoxia</keyword>
  <keyword>phase II trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imidazole</mesh_term>
  </intervention_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/NCT02233387
org study id: 11-36-14/12
nct id: NCT02233387
lead sponsor: 
has dmc: Yes
The aim of this study is:

        1. to determine if tumor hypoxia can be accurately visualised with [18F]HX4 PET imaging in
           cervix cancer,

        2. to correlate the [18F]HX4 PET images with blood and tissue markers,

        3. to investigate the quality and optimal timing of [18F]HX4 PET images,

        4. to compare [18F]HX4 PET uptake with [18F]FDG PET uptake before and after treatment and

        5. analyze correlation with responses
Tumor hypoxia is the situation where tumor cells are or have been deprived of oxygen. Hypoxic
      tumor cells are usually more resistant to radiotherapy and chemotherapy and more likely to
      develop metastasis. In Cervix cancer, tumor hypoxia is known to be an important prognostic
      factor for long term survival. [18F]HX4 is being developed as a diagnostic
      radiopharmaceutical for PET imaging to find a marker for hypoxia that can be used in standard
      clinical practice. Current hypoxia tracers lack reliable image quality and kinetics. Because
      of the short half life and clearance, the investigators expect that [18F]HX4 will have a
      higher tumor to background ratio than current nitro-imidazole hypoxia markers such as
      [18F]-misonidazole. In a recent phase 1 clinical study from van Loon et al, PET-imaging with
      [18F]HX4 was feasible without any toxicity. The clinical use of a reliable, non-invasive and
      easy to use hypoxia imaging agent could allow selection of patients most likely to benefit
      from hypoxia modifying therapies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Visualisation of tumor hypoxia with [18F] HX4 PET imaging
time frame: 2 year
description: Visualisation of tumor hypoxia with [18F] HX4 PET imaging
measure: Observation of spatial and temporal stability of [18F] HX4 PET images
time frame: 2 year
description: Observation of spatial and temporal stability of [18F] HX4 PET images
measure: Correlations with Complete Remission rates at 3 months restaging evaluation
time frame: 2 year
description: Correlations with Complete Remission rates at 3 months restaging evaluation
measure: Image quality of [18F] HX4-PET at different time points
time frame: 2 year
description: Image quality of [18F] HX4-PET at different time points
measure: Kinetic analysis of HX4
time frame: 2 year
description: Kinetic analysis of HX4
measure: Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX)
time frame: 2 year
description: Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX)
measure: Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes
time frame: 2 year
description: Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes
measure: Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment
time frame: 2 year
description: Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment
measure: Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment
time frame: 2 year
description: Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment
arm group label: [18F] HX4 PET imaging
arm group type: Experimental
description: injection with [18F] HX4 and PET imaging at baseline and after 20 Gy radiotherapy
intervention type: Other
intervention name: injection with [18F] HX4 and PET imaging
description: A standard clinical [18F]FDG PET-CT will be performed for the radiotherapy planning.
After a minimum time interval of 24 hours, baseline [18F]HX4 PET scans will be performed:
Based on the phase I trial1 444 MBq (12 mCi) [18F]HX4 is administrated via a bolus IV injection.
The first image acquisition is started together with the administration of [18F]HX4 (30-40 min dynamic). Static scans are acquired at 90 min, 180 min and 240 min p.i
arm group label: [18F] HX4 PET imaging
other name: 3-[18F]fluoro- 2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1- yl)propan-1-ol
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Philippe Lambin, prof MD PhD
role: Study Director
affiliation: Maastro Clinic, The Netherlands
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Imidazole