<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/NCT03831243</url>
  </required_header>
  <id_info>
    <org_study_id>CTOR18072GZA</org_study_id>
    <nct_id>NCT03831243</nct_id>
  </id_info>
  <brief_title>A Trial to Improve Quality of Life With Stereotactic Body Radiotherapy for Patients With Painful Bone Metastases</brief_title>
  <acronym>ROBOMET</acronym>
  <official_title>A Phase III Randomized-controlled, Single-blind Trial to Improve Quality of Life With Stereotactic Body Radiotherapy for Patients With Painful Bone Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Research Antwerp</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Research Antwerp</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>
      This is a phase III randomized-controlled, single-blind study comparing the standard schedule&#xD;
      for antalgic radiotherapy of a single fraction of 8.0 Gy delivered through three-dimensional&#xD;
      conformal radiotherapy (3D-CRT) to a single fraction of 20.0 Gy delivered through&#xD;
      stereotactic body radiotherapy (SBRT). The primary aim of this trial is to double the&#xD;
      complete response rate. Secondary aims are to compare general response rates, duration of&#xD;
      pain response, acute and late toxicity, HRQoL through patient-reported outcome measures&#xD;
      (PROMs), pain flare, and re-irradiation need.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 9, 2019</start_date>
  <completion_date type="Anticipated">March 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>All subjects will be randomly assigned in a 1:1 ratio to receive either a single fraction of 8.0 Gy to the painful bone metastasis through 3D-CRT (control arm) or a single fraction of 20.0 Gy to the painful bone metastasis through SBRT (experimental arm).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain response</measure>
    <time_frame>4 weeks after RT visit</time_frame>
    <description>Pain response at the treated index site at 1 month after radiotherapy (RT), as defined by the consensus statement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of pain flare</measure>
    <time_frame>24-48 hours after radiotherapy</time_frame>
    <description>Number of participants with increase in pain score of 2 or more above baseline at the treated site with stable OMED, or an increase of 25% or more in OMED compared with baseline with the pain score stable or 1 point above baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of pain response</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Time until pain progression (defined as an increase in pain score of 2 or more above baseline at the treated site with stable daily oral morphine equivalent, or an increase of 25% or more in daily oral morphine equivalent (OMED) compared with baseline with the pain score stable or 1 point above baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-irradiation need</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Need for re-irradiation of the treated lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity Measured with CTCAE version 5.0</measure>
    <time_frame>3 months after radiotherapy</time_frame>
    <description>Measured with CTCAE version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late toxicity Measured with CTCAE version 5.0</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Measured with CTCAE version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of treatment on Quality of Life: EORTC quality of life questionnaire (QLQ) BM22</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Using the EORTC quality of life questionnaire for Bone Metastases (QLQ BM22) to measure impact of bone metastases on QoL [min score 0 - max score 100]. A high score represents a high level of symptomatology. The score is calculated by applying a linear transformation on the scores to each answer of the 22 question-long questionnaire (cfr. EORTC mannual).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subsequent Serious Skeletal events</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Incidence of symptomatic pathologic fractures, radiation or surgery to bone, and spinal cord compression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Metastasis to Bone</condition>
  <condition>Radiotherapy</condition>
  <condition>Neoplasm Metastasis</condition>
  <arm_group>
    <arm_group_label>Single fraction of 8 Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The current standard treatment will be prescribed, i.e. a 3D-conformal radiotherapy of a single fraction dose of 8.0 Gy to the metastasis with a planning target volume (PTV) margin for set-up and positioning uncertainties of 1 cm. This can be performed at any linear accelerator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single fraction of 20 Gy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Within the framework of stereotactic body radiotherapy, a single fraction dose of 20.0 Gy will be delivered to the metastasis using a PTV margin of 3-5 mm based on high-precision image-guided radiotherapy (IGRT). Therefore, only linear accelerators with the European Organization for Radiotherapy &amp; Oncology advisory committee on radiation oncology practice (ESTRO-ACROP) specifications for SBRT can be accepted. A risk-adapted approach will be applied, aiming for the highest possible dose no less than 16 Gy, while respecting the tolerances of critical organs at risk (e.g. spinal cord, cauda equina, brainstem etc.).</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic body radiotherapy</intervention_name>
    <description>Treatment will be prescribed to the periphery of the target, i.e. 80% of the dose should cover 95% of the PTV. The organ at risk (OAR) dose constraints will be in accordance with the recommendations from the report of the American Association of Physicists in Medicine (AAPM) task group 101. Image-guidance will consist of cone-beam CT in combination with 6 degrees of freedom corrections using robotic couch.</description>
    <arm_group_label>Single fraction of 20 Gy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>3D-conformal radiotherapy</intervention_name>
    <description>In the standard setting, 95% of the PTV should receive 95% of the prescribed dose while near maximum dose (Dnear-max) in the PTV should not exceed 107%. Image-guidance will consist of portal images showing the relevant bony anatomy.</description>
    <arm_group_label>Single fraction of 8 Gy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed malignancy.&#xD;
&#xD;
          -  Pain score ≥ 2 on a scale from 0 to 10.&#xD;
&#xD;
          -  Radiological or (bone) scintigraphic evidence of bone metastasis at the site of pain.&#xD;
&#xD;
          -  Lesions ≤ 5cm in largest diameter.&#xD;
&#xD;
          -  Per lesion no more than 3 consecutive spine segments involved with one unaffected&#xD;
             vertebral body above and below.&#xD;
&#xD;
          -  No more than 3 painful lesions needing treatment.&#xD;
&#xD;
          -  Life expectancy estimated at &gt; 3 months.&#xD;
&#xD;
          -  Patients who have received the information sheet and signed the informed consent form.&#xD;
&#xD;
          -  Patients must be willing to comply with scheduled visits, treatment plan, and other&#xD;
             study procedures.&#xD;
&#xD;
          -  Patients with a public and/or private health insurance coverage.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Myeloma.&#xD;
&#xD;
          -  Bone metastasis in previously irradiated sites.&#xD;
&#xD;
          -  Previous radioisotope treatment for bone metastases.&#xD;
&#xD;
          -  Complicated bone metastasis, i.e. impending and/or existing pathological fracture,&#xD;
             spinal cord compression or cauda equina compression [16].&#xD;
&#xD;
          -  Patients with significantly altered mental status or with psychological, familial,&#xD;
             sociological or geographical condition potential hampering compliance with the study.&#xD;
&#xD;
          -  Individual deprived of liberty or placed under guardianship.&#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>Dirk Verellen, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Iridium Cancer Network</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Piet Dirix, MD PhD</last_name>
    <phone>003234433737</phone>
    <email>piet.dirix@gza.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carole Mercier, MD</last_name>
    <phone>003234433737</phone>
    <email>carole.mercier@gza.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Radiotherapy department, GZA Hospitals</name>
      <address>
        <city>Wilrijk</city>
        <state>Antwerp</state>
        <zip>2610</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Piet Dirix, MD PhD</last_name>
      <phone>003234433737</phone>
      <email>piet.dirix@gza.be</email>
    </contact>
    <contact_backup>
      <last_name>Carole Mercier, MD</last_name>
      <phone>0032344333737</phone>
      <email>carole.mercier@gza.be</email>
    </contact_backup>
    <investigator>
      <last_name>Piet Dirix, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Carole Mercier, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>October 22, 2018</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>December 16, 2020</last_update_submitted>
  <last_update_submitted_qc>December 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stereotactic Body Radiotherapy</keyword>
  <keyword>Spinal metastases</keyword>
  <keyword>Bone metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms, Second Primary</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/NCT03831243
org study id: CTOR18072GZA
nct id: NCT03831243
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a phase III randomized-controlled, single-blind study comparing the standard schedule
      for antalgic radiotherapy of a single fraction of 8.0 Gy delivered through three-dimensional
      conformal radiotherapy (3D-CRT) to a single fraction of 20.0 Gy delivered through
      stereotactic body radiotherapy (SBRT). The primary aim of this trial is to double the
      complete response rate. Secondary aims are to compare general response rates, duration of
      pain response, acute and late toxicity, HRQoL through patient-reported outcome measures
      (PROMs), pain flare, and re-irradiation need.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All subjects will be randomly assigned in a 1:1 ratio to receive either a single fraction of 8.0 Gy to the painful bone metastasis through 3D-CRT (control arm) or a single fraction of 20.0 Gy to the painful bone metastasis through SBRT (experimental arm).
primary purpose: Treatment
masking: Single (Participant)
measure: Pain response
time frame: 4 weeks after RT visit
description: Pain response at the treated index site at 1 month after radiotherapy (RT), as defined by the consensus statement.
measure: Incidence of pain flare
time frame: 24-48 hours after radiotherapy
description: Number of participants with increase in pain score of 2 or more above baseline at the treated site with stable OMED, or an increase of 25% or more in OMED compared with baseline with the pain score stable or 1 point above baseline
measure: Duration of pain response
time frame: 2 years after radiotherapy
description: Time until pain progression (defined as an increase in pain score of 2 or more above baseline at the treated site with stable daily oral morphine equivalent, or an increase of 25% or more in daily oral morphine equivalent (OMED) compared with baseline with the pain score stable or 1 point above baseline)
measure: Re-irradiation need
time frame: 2 years after radiotherapy
description: Need for re-irradiation of the treated lesion
measure: Acute toxicity Measured with CTCAE version 5.0
time frame: 3 months after radiotherapy
description: Measured with CTCAE version 5.0
measure: Late toxicity Measured with CTCAE version 5.0
time frame: 2 years after radiotherapy
description: Measured with CTCAE version 5.0
measure: Impact of treatment on Quality of Life: EORTC quality of life questionnaire (QLQ) BM22
time frame: 2 years after radiotherapy
description: Using the EORTC quality of life questionnaire for Bone Metastases (QLQ BM22) to measure impact of bone metastases on QoL [min score 0 - max score 100]. A high score represents a high level of symptomatology. The score is calculated by applying a linear transformation on the scores to each answer of the 22 question-long questionnaire (cfr. EORTC mannual).
measure: Number of Subsequent Serious Skeletal events
time frame: 2 years after radiotherapy
description: Incidence of symptomatic pathologic fractures, radiation or surgery to bone, and spinal cord compression.
arm group label: Single fraction of 8 Gy
arm group type: Active Comparator
description: The current standard treatment will be prescribed, i.e. a 3D-conformal radiotherapy of a single fraction dose of 8.0 Gy to the metastasis with a planning target volume (PTV) margin for set-up and positioning uncertainties of 1 cm. This can be performed at any linear accelerator.
arm group label: Single fraction of 20 Gy
arm group type: Experimental
description: Within the framework of stereotactic body radiotherapy, a single fraction dose of 20.0 Gy will be delivered to the metastasis using a PTV margin of 3-5 mm based on high-precision image-guided radiotherapy (IGRT). Therefore, only linear accelerators with the European Organization for Radiotherapy & Oncology advisory committee on radiation oncology practice (ESTRO-ACROP) specifications for SBRT can be accepted. A risk-adapted approach will be applied, aiming for the highest possible dose no less than 16 Gy, while respecting the tolerances of critical organs at risk (e.g. spinal cord, cauda equina, brainstem etc.).
intervention type: Radiation
intervention name: Stereotactic body radiotherapy
description: Treatment will be prescribed to the periphery of the target, i.e. 80% of the dose should cover 95% of the PTV. The organ at risk (OAR) dose constraints will be in accordance with the recommendations from the report of the American Association of Physicists in Medicine (AAPM) task group 101. Image-guidance will consist of cone-beam CT in combination with 6 degrees of freedom corrections using robotic couch.
arm group label: Single fraction of 20 Gy
intervention type: Radiation
intervention name: 3D-conformal radiotherapy
description: In the standard setting, 95% of the PTV should receive 95% of the prescribed dose while near maximum dose (Dnear-max) in the PTV should not exceed 107%. Image-guidance will consist of portal images showing the relevant bony anatomy.
arm group label: Single fraction of 8 Gy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dirk Verellen, PhD
role: Study Director
affiliation: Iridium Cancer Network
last name: Piet Dirix, MD PhD
phone: 003234433737
email: piet.dirix@gza.be
last name: Carole Mercier, MD
phone: 003234433737
email: carole.mercier@gza.be
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Neoplasms, Second Primary