<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/NCT03284619</url>
  </required_header>
  <id_info>
    <org_study_id>MR-Linac-CIP-001 Version 2.0</org_study_id>
    <secondary_id>NL60984.041.17</secondary_id>
    <nct_id>NCT03284619</nct_id>
  </id_info>
  <brief_title>First-In Man (FIM) Study MR-Linac</brief_title>
  <acronym>FIM MR-Linac</acronym>
  <official_title>First-In Man (FIM) Study MR-Linac</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nucletron Operations BV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Factory CRO for Medical Devices B.V.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nucletron Operations BV</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>
      Investigational device is the Magnetic resonance imager linear accelerator. Five (5) patients&#xD;
      with bone metastases will be treated with palliative intention in this study. The goal is to&#xD;
      confirm the pre-clinically demonstrated technical accuracy and safety of the newly developed&#xD;
      MR-Linac in the clinical setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center prospective proof of concept study including accuracy and safety&#xD;
      aspects according to R-IDEAL stage 1 criteria. Five (5) patients with bone metastases will be&#xD;
      treated with palliative intention in this study. Treatment will consist of a single fraction.&#xD;
&#xD;
      The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic&#xD;
      quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for&#xD;
      improved targeting. This enables on-line treatment optimization for precise radiation&#xD;
      delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at&#xD;
      the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy&#xD;
      while optimally sparing normal tissues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Actual">September 8, 2017</completion_date>
  <primary_completion_date type="Actual">July 11, 2017</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>
    <intervention_model_description>Proof of concept including accuracy and safety aspects according to R-IDEAL stage 1 criteria</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of the treatment system (a dose distribution accuracy ≤ 5% will be considered acceptable). Incidence of acute toxicity (CTCAE grade 2 are higher) and incidence of Serious (unexpected) Adverse Events will be measured.</measure>
    <time_frame>During treatment (Day 0). For patient safety patients will be contacted at day 1, week 2 and week 12 after treatment.</time_frame>
    <description>Safety of the system: System behaves in accordance with the workflow and risk mitigation plan, Dosimetric safety: An independent dosimetry check before start irradiation (Oncentra) and an independent dosimetry during irradiation (second chamber) will be used. For the overall process a dose distribution accuracy ≤ 5% will be considered acceptable.&#xD;
Patients safety: by reporting any acute toxicity &gt; grade 2 (according CTCAE version 4.0 for acute toxicity) and any Serious (Unexpected) Adverse Events (S(U)AE) within 12 weeks after treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometrical accuracy of targeting by online MR imaging</measure>
    <time_frame>During treatment (day 0)</time_frame>
    <description>Geometrical accuracy: will be checked online by using the MRI in combination with VolumeTool visualization and off-line by comparison of the EPID beam data with the prescribed beam data. A positioning error of ≤ 5 mm will be considered acceptable</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Descriptive analysis of the clinical workflow by keeping a log book for the entire procedure.</measure>
    <time_frame>During treatment (day 0)</time_frame>
    <description>Feasibility of the clinical workflow: by keeping a log book for the entire procedure. The validation of radiation delivery includes assessing the hardware performance and the See-Plan-Treat work flow for on-line MRI guided adaptive radiotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients comfort</measure>
    <time_frame>immediately after treatment (day 0)</time_frame>
    <description>Patient comfort during the MR-Linac treatment: by patient questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Bone Metastases</condition>
  <arm_group>
    <arm_group_label>treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm study, 5 patient with bone metastasis will be enrolled for palliative treatment with the Magnetic resonance imager linear accelerator (MR-Linac).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Magnetic resonance imager linear accelerator</intervention_name>
    <description>The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for improved targeting. This enables on-line treatment optimization for precise radiation delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy while optimally sparing normal tissues.</description>
    <arm_group_label>treatment arm</arm_group_label>
    <other_name>MR-Linac</other_name>
    <other_name>Unity</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to be eligible to participate in this study, a patient must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          -  Painful bone metastases in the lumbar spine&#xD;
&#xD;
          -  Radiographic evidence of bone metastases&#xD;
&#xD;
          -  Histologic proof of malignancy (primary carcinoma)&#xD;
&#xD;
          -  Karnofsky Performance Score ≥ 50&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A potential subject who meets any of the following criteria will be excluded from&#xD;
        participation in this study:&#xD;
&#xD;
          -  Prior radiation therapy within the region planned to be irradiated&#xD;
&#xD;
          -  Contraindication for MRI according to screening protocol radiology department UMCU&#xD;
             (e.g. cardiac pacemakers, and defibrillators, artificial heart valves or cochlear&#xD;
             implants,&#xD;
             https://richtlijn.mijnumc.nl/Beeld/MRI/Paginas/MRI-Veiligheid-Contra-indicaties.aspx&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Standard systemic anti-cancer therapy or radionuclide therapy within 48 hours before&#xD;
             or after treatment.&#xD;
&#xD;
          -  Any other type of not standard systemic anti-cancer treatment, except for endocrine&#xD;
             treatment.&#xD;
&#xD;
          -  Unstable spine requiring surgical stabilization&#xD;
&#xD;
          -  Neurological deficit due to bone metastasis&#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>Ina Jürgenliemk-Schulz, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMCU</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Centre Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>June 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>March 27, 2018</last_update_submitted>
  <last_update_submitted_qc>March 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</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/NCT03284619
org study id: MR-Linac-CIP-001 Version 2.0
secondary id: NL60984.041.17
nct id: NCT03284619
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Investigational device is the Magnetic resonance imager linear accelerator. Five (5) patients
      with bone metastases will be treated with palliative intention in this study. The goal is to
      confirm the pre-clinically demonstrated technical accuracy and safety of the newly developed
      MR-Linac in the clinical setting.
This is a single center prospective proof of concept study including accuracy and safety
      aspects according to R-IDEAL stage 1 criteria. Five (5) patients with bone metastases will be
      treated with palliative intention in this study. Treatment will consist of a single fraction.

      The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic
      quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for
      improved targeting. This enables on-line treatment optimization for precise radiation
      delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at
      the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy
      while optimally sparing normal tissues.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Proof of concept including accuracy and safety aspects according to R-IDEAL stage 1 criteria
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of the treatment system (a dose distribution accuracy ≤ 5% will be considered acceptable). Incidence of acute toxicity (CTCAE grade 2 are higher) and incidence of Serious (unexpected) Adverse Events will be measured.
time frame: During treatment (Day 0). For patient safety patients will be contacted at day 1, week 2 and week 12 after treatment.
description: Safety of the system: System behaves in accordance with the workflow and risk mitigation plan, Dosimetric safety: An independent dosimetry check before start irradiation (Oncentra) and an independent dosimetry during irradiation (second chamber) will be used. For the overall process a dose distribution accuracy ≤ 5% will be considered acceptable.
Patients safety: by reporting any acute toxicity > grade 2 (according CTCAE version 4.0 for acute toxicity) and any Serious (Unexpected) Adverse Events (S(U)AE) within 12 weeks after treatment
measure: Geometrical accuracy of targeting by online MR imaging
time frame: During treatment (day 0)
description: Geometrical accuracy: will be checked online by using the MRI in combination with VolumeTool visualization and off-line by comparison of the EPID beam data with the prescribed beam data. A positioning error of ≤ 5 mm will be considered acceptable
measure: Descriptive analysis of the clinical workflow by keeping a log book for the entire procedure.
time frame: During treatment (day 0)
description: Feasibility of the clinical workflow: by keeping a log book for the entire procedure. The validation of radiation delivery includes assessing the hardware performance and the See-Plan-Treat work flow for on-line MRI guided adaptive radiotherapy.
measure: Patients comfort
time frame: immediately after treatment (day 0)
description: Patient comfort during the MR-Linac treatment: by patient questionnaire.
arm group label: treatment arm
arm group type: Experimental
description: Single arm study, 5 patient with bone metastasis will be enrolled for palliative treatment with the Magnetic resonance imager linear accelerator (MR-Linac).
intervention type: Device
intervention name: Magnetic resonance imager linear accelerator
description: The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for improved targeting. This enables on-line treatment optimization for precise radiation delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy while optimally sparing normal tissues.
arm group label: treatment arm
other name: MR-Linac
other name: Unity
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ina Jürgenliemk-Schulz, MD, PhD
role: Principal Investigator
affiliation: UMCU
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
sharing ipd: No