<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/NCT02987153</url>
  </required_header>
  <id_info>
    <org_study_id>15-298</org_study_id>
    <nct_id>NCT02987153</nct_id>
  </id_info>
  <brief_title>Kypho-Intra Operative Radiation Therapy (IORT) for Localized Spine Metastasis, Phase I/II Study</brief_title>
  <acronym>Kypho-IORT</acronym>
  <official_title>Kypho-Intra Operative Radiation Therapy (IORT) for Localized Spine Metastasis, Phase I/II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwell Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwell Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Kypho-IORT is a novel approach to combine kyphoplasty, a minimally invasive procedure, with a&#xD;
      single dose of intraoperative radiotherapy (IORT) for the treatment of unstable or&#xD;
      potentially unstable spinal cord metastases. The primary objective is to evaluate the&#xD;
      response rate of pain control when combining kyphoplasty, a minimally invasive procedure,&#xD;
      with a single dose of intraoperative radio- therapy (IORT) for the treatment of spinal cord&#xD;
      metastases. Secondary objectives are (i.) to determine feasibility for unstable or potential&#xD;
      unstable spine metastases; (ii.) to determine tolerability/side effects of the IORT within 90&#xD;
      days post-procedure; (iii.) to determine which clinical factors are prognostic of vertebral&#xD;
      compression fracture&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately 20% of patients with spine metastasis present with unstable lesions, which&#xD;
      represent a common therapeutic dilemma in patients with advanced stage cancer and limited&#xD;
      survival time. Management necessitates spinal stabilization surgery such as laminectomy,&#xD;
      vertebroplasty, or kyphoplasty for mechanical back pain control and irradiation for the&#xD;
      underlying malignant process. Because of the limited survival time of patients with&#xD;
      metastatic cancer, novel, more convenient treatment concepts to shorten the overall treatment&#xD;
      time or hospitalization are desirable. We developed a novel approach to combine kyphoplasty,&#xD;
      a minimally invasive procedure, with a single dose of intraoperative radio- therapy (IORT)&#xD;
      for the treatment of spinal cord metastases.&#xD;
&#xD;
      Patients treated with Kypho-IORT will receive a prescribed dose of 8 Gy in 1 fraction from&#xD;
      The Intrabeam® Photon Radiosurgery System source. The target volume includes only the tumor.&#xD;
      The technique of the operation and the delivery of radiotherapy has been described and&#xD;
      published previously. TARGiT Academy training and requisite test cases have been completed&#xD;
      prior to enrolling subjects on this study. The balloon kyphoplasty, which is an advancement&#xD;
      of the vertebroplasty, is a treatment option for fractured vertebral bodies which utilizes&#xD;
      bone cement to provide needed support.&#xD;
&#xD;
      Outcome measures will include complete or partial pain relief or a stable response at the&#xD;
      index site requiring no increase in narcotic pain medication. Therefore, patients with&#xD;
      complete or partial pain relief will be considered responders. Patients with complete or&#xD;
      partial pain relief at the index site but a progressive response at the secondary site(s)&#xD;
      will be considered non-responders.&#xD;
&#xD;
      Quality of Life Measurements. It is hypothesized that quality of life (QOL) will improve&#xD;
      after Kypho-IORT due to rapid and durable pain control after spine treatment. In the current&#xD;
      study, we will measure the QOL [EORTC QLQ-C30 (version 3)], the Brief Pain Inventory (BPI),&#xD;
      ambulation , and steroid and narcotic use pre- and post-procedure at 1-week, 3-month,&#xD;
      6-month, 9-month, 1-year, and 2-year intervals. The involved spine will be imaged at 3-month&#xD;
      intervals up to one year, and at 2 years post-procedure.&#xD;
&#xD;
      All the evidence to date supports the description of the Intrabeam as delivering an accurate&#xD;
      and reliable dose. Physicists on site will be responsible for verifying the miniature x-ray&#xD;
      source is operational prior to use and setting up the parameters within the control console&#xD;
      software for treatment delivery. During the procedure, the control console monitors the&#xD;
      system for safe and accurate dose delivery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">October 2022</completion_date>
  <primary_completion_date type="Actual">July 2022</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>To evaluate pain control</measure>
    <time_frame>90 days</time_frame>
    <description>To evaluate the response rate of pain control when combining kyphoplasty, a minimally invasive procedure, with a single dose of intraoperative radio- therapy (IORT) for the treatment of spinal cord metastases.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility of Kypho-IORT as treatment modality</measure>
    <time_frame>90 days</time_frame>
    <description>To determine the feasibility of delivered Kypho-IORT for unstable or potential unstable spine metastases.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability/side effects</measure>
    <time_frame>90 days</time_frame>
    <description>To determine tolerability/side effects of the IORT based on defined MTD criteria (wound healing problems, infection, osteoradionecrosis, nerve and spinal cord damage, pathological fracture, secondary fractures/sintering progression and symptomatic or asymptomatic cement leakage within 90 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local tumor control</measure>
    <time_frame>2 years</time_frame>
    <description>Local tumor control is defined as no recurrent tumor in the treated lesion. Patients will be regularly monitored as per the site's policy provided this meets the minimum trial criteria for follow-up with physical examination 1 week post treatment, and at 3 months, 6 months, 1 year, and 2 years post-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival will be the time interval between enrollment and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of quality of life.</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluate the potential benefit of Kypho-IORT on change in and overall quality of life, in pain as measured by the Brief Pain Inventory (BPI); Ambulation, and EORTC QLQ-C30 (version 3).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steroid and narcotic use.</measure>
    <time_frame>2 years</time_frame>
    <description>The average daily morphine equivalent (mgs) used.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">22</enrollment>
  <condition>Spinal Metastases</condition>
  <arm_group>
    <arm_group_label>KYPHO-IORT - 10 Gy and Kyphoplasty</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intra-operative radiation therapy followed by standard kyphoplasty</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Kypho-IORT</intervention_name>
    <description>The radiation source is inserted into the lesion and switched on for a few minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and clinical applications of this device have been well studied.</description>
    <arm_group_label>KYPHO-IORT - 10 Gy and Kyphoplasty</arm_group_label>
    <other_name>Intrabeam® Photon Radiosurgery System</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Karnofsky Index ≥ 60.&#xD;
&#xD;
          -  History/physical examination within 4 weeks prior to procedure.&#xD;
&#xD;
          -  Imaging of the involved spine within 8 weeks prior to procedure to determine the&#xD;
             extent of the spine involvement.&#xD;
&#xD;
          -  Numerical Rating Pain Scale within 4 week prior to procedure (score must be ≥ 5 for at&#xD;
             least one of the planned sites for spinal IORT.&#xD;
&#xD;
          -  Neurological examination within 4 week prior to procedure to rule out rapid neurologic&#xD;
             decline.&#xD;
&#xD;
          -  Spine Instability Neoplastic Score (SINS score) = ≤12.&#xD;
&#xD;
          -  Negative serum pregnancy test within 4 weeks prior to procedure for women of&#xD;
             childbearing potential.&#xD;
&#xD;
          -  Women of childbearing potential and male participants who are sexually active must&#xD;
             agree to use a medically effective means of birth control.&#xD;
&#xD;
          -  The patient must have localized spine metastasis from the T5 to L5 levels by a&#xD;
             screening imaging study [bone scan, PET, CT, or MRI] (a solitary spine metastasis; two&#xD;
             separate spine levels; or up to 3 separate sites are permitted). Each of the separate&#xD;
             sites have a maximal involvement of ONE vertebral body. Patients can have other&#xD;
             visceral metastasis.&#xD;
&#xD;
          -  Patients must provide study specific informed consent prior to study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Spine instability due to a compression fracture; SINS score &gt;12.&#xD;
&#xD;
          -  Frank spinal cord compression or displacement or epidural compression within 3 mm of&#xD;
             the spinal cord&#xD;
&#xD;
          -  Patients with rapid neurologic decline&#xD;
&#xD;
          -  Bony retropulsion causing neurologic abnormality&#xD;
&#xD;
          -  Patients allergic to contrast dye used in MRIs or CT scans or who cannot be&#xD;
             premedicated for the use of contrast dye&#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>Maged Ghaly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwell Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwell Health</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwell Health</investigator_affiliation>
    <investigator_full_name>Maged Ghaly</investigator_full_name>
    <investigator_title>Asst. Professor of Radiation Medicine</investigator_title>
  </responsible_party>
  <keyword>Kyphoplasty</keyword>
  <keyword>Spinal metastases</keyword>
  <keyword>IORT</keyword>
  <keyword>Intraoperative radiation therapy</keyword>
  <keyword>Pain management</keyword>
  <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>
    <ipd_description>No plan to share data</ipd_description>
  </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/NCT02987153
org study id: 15-298
nct id: NCT02987153
lead sponsor: 
has dmc: Yes
Kypho-IORT is a novel approach to combine kyphoplasty, a minimally invasive procedure, with a
      single dose of intraoperative radiotherapy (IORT) for the treatment of unstable or
      potentially unstable spinal cord metastases. The primary objective is to evaluate the
      response rate of pain control when combining kyphoplasty, a minimally invasive procedure,
      with a single dose of intraoperative radio- therapy (IORT) for the treatment of spinal cord
      metastases. Secondary objectives are (i.) to determine feasibility for unstable or potential
      unstable spine metastases; (ii.) to determine tolerability/side effects of the IORT within 90
      days post-procedure; (iii.) to determine which clinical factors are prognostic of vertebral
      compression fracture
Approximately 20% of patients with spine metastasis present with unstable lesions, which
      represent a common therapeutic dilemma in patients with advanced stage cancer and limited
      survival time. Management necessitates spinal stabilization surgery such as laminectomy,
      vertebroplasty, or kyphoplasty for mechanical back pain control and irradiation for the
      underlying malignant process. Because of the limited survival time of patients with
      metastatic cancer, novel, more convenient treatment concepts to shorten the overall treatment
      time or hospitalization are desirable. We developed a novel approach to combine kyphoplasty,
      a minimally invasive procedure, with a single dose of intraoperative radio- therapy (IORT)
      for the treatment of spinal cord metastases.

      Patients treated with Kypho-IORT will receive a prescribed dose of 8 Gy in 1 fraction from
      The Intrabeam® Photon Radiosurgery System source. The target volume includes only the tumor.
      The technique of the operation and the delivery of radiotherapy has been described and
      published previously. TARGiT Academy training and requisite test cases have been completed
      prior to enrolling subjects on this study. The balloon kyphoplasty, which is an advancement
      of the vertebroplasty, is a treatment option for fractured vertebral bodies which utilizes
      bone cement to provide needed support.

      Outcome measures will include complete or partial pain relief or a stable response at the
      index site requiring no increase in narcotic pain medication. Therefore, patients with
      complete or partial pain relief will be considered responders. Patients with complete or
      partial pain relief at the index site but a progressive response at the secondary site(s)
      will be considered non-responders.

      Quality of Life Measurements. It is hypothesized that quality of life (QOL) will improve
      after Kypho-IORT due to rapid and durable pain control after spine treatment. In the current
      study, we will measure the QOL [EORTC QLQ-C30 (version 3)], the Brief Pain Inventory (BPI),
      ambulation , and steroid and narcotic use pre- and post-procedure at 1-week, 3-month,
      6-month, 9-month, 1-year, and 2-year intervals. The involved spine will be imaged at 3-month
      intervals up to one year, and at 2 years post-procedure.

      All the evidence to date supports the description of the Intrabeam as delivering an accurate
      and reliable dose. Physicists on site will be responsible for verifying the miniature x-ray
      source is operational prior to use and setting up the parameters within the control console
      software for treatment delivery. During the procedure, the control console monitors the
      system for safe and accurate dose delivery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate pain control
time frame: 90 days
description: To evaluate the response rate of pain control when combining kyphoplasty, a minimally invasive procedure, with a single dose of intraoperative radio- therapy (IORT) for the treatment of spinal cord metastases.
measure: Feasibility of Kypho-IORT as treatment modality
time frame: 90 days
description: To determine the feasibility of delivered Kypho-IORT for unstable or potential unstable spine metastases.
measure: Tolerability/side effects
time frame: 90 days
description: To determine tolerability/side effects of the IORT based on defined MTD criteria (wound healing problems, infection, osteoradionecrosis, nerve and spinal cord damage, pathological fracture, secondary fractures/sintering progression and symptomatic or asymptomatic cement leakage within 90 days.
measure: Local tumor control
time frame: 2 years
description: Local tumor control is defined as no recurrent tumor in the treated lesion. Patients will be regularly monitored as per the site's policy provided this meets the minimum trial criteria for follow-up with physical examination 1 week post treatment, and at 3 months, 6 months, 1 year, and 2 years post-treatment.
measure: Overall survival
time frame: 2 years
description: Overall survival will be the time interval between enrollment and death.
measure: Measures of quality of life.
time frame: 2 years
description: Evaluate the potential benefit of Kypho-IORT on change in and overall quality of life, in pain as measured by the Brief Pain Inventory (BPI); Ambulation, and EORTC QLQ-C30 (version 3).
measure: Steroid and narcotic use.
time frame: 2 years
description: The average daily morphine equivalent (mgs) used.
arm group label: KYPHO-IORT - 10 Gy and Kyphoplasty
arm group type: Experimental
description: Intra-operative radiation therapy followed by standard kyphoplasty
intervention type: Radiation
intervention name: Kypho-IORT
description: The radiation source is inserted into the lesion and switched on for a few minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and clinical applications of this device have been well studied.
arm group label: KYPHO-IORT - 10 Gy and Kyphoplasty
other name: Intrabeam® Photon Radiosurgery System
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maged Ghaly, MD
role: Principal Investigator
affiliation: Northwell Health
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Northwell Health
investigator full name: Maged Ghaly
investigator title: Asst. Professor of Radiation Medicine
mesh term: Neoplasm Metastasis
sharing ipd: No
ipd description: No plan to share data