<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/NCT03247127</url>
  </required_header>
  <id_info>
    <org_study_id>KMUHIRB-E(II)20170081</org_study_id>
    <nct_id>NCT03247127</nct_id>
  </id_info>
  <brief_title>Memory Preservation of Hippocampal Avoidance Whole Brain Radiotherapy</brief_title>
  <official_title>The Memory Preservation Study of Whole Brain Radiotherapy With Hippocampal Avoidance for Patients With Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The study aimed to investigate the memory preservation and neurocognitive function protection&#xD;
      of hippocampal avoidance whole brain radiotherapy (HA-WBRT) among people who speak Mandarin&#xD;
      Chinese or Taiwanese.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brain metastasis is very common, about 30% incidence rate for all patients with a diagnosis&#xD;
      of cancer. The rising incidence of brain metastasis is most likely due to recent advances in&#xD;
      systemic therapy, and use of magnetic resonance imaging (MRI). The most common primary site&#xD;
      is the lung followed by breast. One of the standard treatments is whole brain radiotherapy;&#xD;
      it can prolong the decline of neurocognitive function and improve quality of life. However,&#xD;
      it can also cause decline in neurocognitive function as a late sequela. Memory impairment is&#xD;
      the main cognitive function that affected by radiotherapy, and the neuronal stem cells&#xD;
      located at hippocampal subgranular zone are highly sensitive to radiotherapy. There have been&#xD;
      large randomized trials confirming that by HA-WBRT, the neurocognitive function decline can&#xD;
      be reclaimed. In Taiwan, HA-WBRT is a popular and emerging treatment. However, not much study&#xD;
      focused on its effects on neurocognitive function. The study is aimed to objectively&#xD;
      investigate the memory preservation and neurocognitive function protection of HA-WBRT in&#xD;
      people speaking Mandarin Chinese or Taiwanese by utilizing neurocognitive function test and&#xD;
      QoL questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</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>Hippocampal avoidance -whole brain radiotherapy(HA-WBRT), which delivers radiation to whole brain and moreover, to reduce mean dose to hippocampal neural stem-cell compartment to minimize the neurocognitive function impairment</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of Memory immediate recall and delayed recall</measure>
    <time_frame>From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete.</time_frame>
    <description>The memory battery is using Wechsler Memory Scale (Chinese), including Logical Memory I &amp; II, Word Lists Ⅰ &amp; II, Faces Ⅰ and spatial span.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of general cognitive function</measure>
    <time_frame>From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete.</time_frame>
    <description>General cognitive function are tested using cognitive abilities screening instrument, CASI for screening and to test cognitive function as a whole.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of Quality of life</measure>
    <time_frame>From baseline to 4 months after RT complete, the participants are requested to fill in the questionnaire of quality of life at baseline before radiotherapy begins, and 2 months after radiotherapy complete and 4 months after radiotherapy complete.</time_frame>
    <description>Quality of life are assessed using The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Brain Metastases</condition>
  <condition>Neurocognitive Function</condition>
  <arm_group>
    <arm_group_label>HA-WBRT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with brain metastases outside a 5-mm margin around either hippocampus and are eligible to this study will receive hippocampal avoidance whole brain radiotherapy 30 gray (Gy) in 10 fractions. The primary endpoint is Wechsler Memory Scale (Chinese) and cognitive abilities screening instrument (CASI) at 4 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hippocampal avoidance whole brain radiotherapy</intervention_name>
    <description>Planning target volume(PTV) for whole brain is Whole brain parenchyma plus2mm margin excluding metastases and HA region, 30Gy in 10 fractions will be delivered to PTVwhole brain. Bilateral Hippocampus will be contoured according to Radiation Therapy Oncology Group 0933 and hippocampal avoidance region is Hippocampi + 5mm margin. According to Radiation Therapy Oncology Group 0933 trial, dose to 100% of the hippocampus could not exceed 9 Gy, and maximal hippocampal dose could not exceed 16 Gy; dose to 100% of the hippocampus exceeding 10 Gy</description>
    <arm_group_label>HA-WBRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with brain metastases, the brain metastases are located 5mm outside the&#xD;
             hippocampus&#xD;
&#xD;
          -  Pathologically proven diagnosis of nonhematopoietic malignancy other than germ cell&#xD;
             malignancy&#xD;
&#xD;
          -  No psychologic disorders&#xD;
&#xD;
          -  Radiation Therapy Oncology Group recursive partitioning analysis class I or II&#xD;
&#xD;
          -  First or second language: Mandarin Chinese or Taiwanese&#xD;
&#xD;
          -  Signed the inform consensus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than 20 years old&#xD;
&#xD;
          -  Leptomeningeal metastases or hydrocephalus&#xD;
&#xD;
          -  Previous radiotherapy to head and neck region&#xD;
&#xD;
          -  Creatinine &gt;1.5mg/dl&#xD;
&#xD;
          -  More than 2 extracranial metastases&#xD;
&#xD;
          -  Patients who cannot tolerate memory or neurocognitive function test or cannot complete&#xD;
             QoL questionnaire&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pen-Tzu Fang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Radiation Oncology, Kaohsiung Medical University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pen-Tzu Fang, MD</last_name>
    <phone>886-7-3121101</phone>
    <phone_ext>7158</phone_ext>
    <email>ptmonicafang@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fang, Pen-Tzu</name>
      <address>
        <city>Kaohsiung</city>
        <zip>80660</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fang Pen-Tzu, MD</last_name>
      <phone>886-7-3121101</phone>
      <phone_ext>7158</phone_ext>
      <email>ptmonicafang@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <results_reference>
    <citation>Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27.</citation>
    <PMID>25349290</PMID>
  </results_reference>
  <results_reference>
    <citation>Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95. doi: 10.1016/j.ijrobp.2007.03.048.</citation>
    <PMID>17674975</PMID>
  </results_reference>
  <results_reference>
    <citation>Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995 Feb 15;31(4):983-98. doi: 10.1016/0360-3016(94)00550-8.</citation>
    <PMID>7860415</PMID>
  </results_reference>
  <results_reference>
    <citation>DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.</citation>
    <PMID>2725874</PMID>
  </results_reference>
  <results_reference>
    <citation>Ghia A, Tome WA, Thomas S, Cannon G, Khuntia D, Kuo JS, Mehta MP. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):971-7. doi: 10.1016/j.ijrobp.2007.02.016. Epub 2007 Apr 18.</citation>
    <PMID>17446005</PMID>
  </results_reference>
  <results_reference>
    <citation>Gondi V, Tome WA, Marsh J, Struck A, Ghia A, Turian JV, Bentzen SM, Kuo JS, Khuntia D, Mehta MP. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933. Radiother Oncol. 2010 Jun;95(3):327-31. doi: 10.1016/j.radonc.2010.02.030. Epub 2010 Apr 12.</citation>
    <PMID>20392503</PMID>
  </results_reference>
  <results_reference>
    <citation>Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, Khuntia D, Tome WA. Hippocampal-sparing whole-brain radiotherapy: a &quot;how-to&quot; technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1244-52. doi: 10.1016/j.ijrobp.2010.01.039.</citation>
    <PMID>20598457</PMID>
  </results_reference>
  <results_reference>
    <citation>Gutierrez AN, Westerly DC, Tome WA, Jaradat HA, Mackie TR, Bentzen SM, Khuntia D, Mehta MP. Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):589-97. doi: 10.1016/j.ijrobp.2007.05.038.</citation>
    <PMID>17869672</PMID>
  </results_reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>August 26, 2018</last_update_submitted>
  <last_update_submitted_qc>August 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hippocampal avoidance whole brain radiotherapy (HA-WBRT)</keyword>
  <keyword>brain metastases</keyword>
  <keyword>memory preservation</keyword>
  <keyword>neurocognitive function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</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/NCT03247127
org study id: KMUHIRB-E(II)20170081
nct id: NCT03247127
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study aimed to investigate the memory preservation and neurocognitive function protection
      of hippocampal avoidance whole brain radiotherapy (HA-WBRT) among people who speak Mandarin
      Chinese or Taiwanese.
Brain metastasis is very common, about 30% incidence rate for all patients with a diagnosis
      of cancer. The rising incidence of brain metastasis is most likely due to recent advances in
      systemic therapy, and use of magnetic resonance imaging (MRI). The most common primary site
      is the lung followed by breast. One of the standard treatments is whole brain radiotherapy;
      it can prolong the decline of neurocognitive function and improve quality of life. However,
      it can also cause decline in neurocognitive function as a late sequela. Memory impairment is
      the main cognitive function that affected by radiotherapy, and the neuronal stem cells
      located at hippocampal subgranular zone are highly sensitive to radiotherapy. There have been
      large randomized trials confirming that by HA-WBRT, the neurocognitive function decline can
      be reclaimed. In Taiwan, HA-WBRT is a popular and emerging treatment. However, not much study
      focused on its effects on neurocognitive function. The study is aimed to objectively
      investigate the memory preservation and neurocognitive function protection of HA-WBRT in
      people speaking Mandarin Chinese or Taiwanese by utilizing neurocognitive function test and
      QoL questionnaire.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Hippocampal avoidance -whole brain radiotherapy(HA-WBRT), which delivers radiation to whole brain and moreover, to reduce mean dose to hippocampal neural stem-cell compartment to minimize the neurocognitive function impairment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Changes of Memory immediate recall and delayed recall
time frame: From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete.
description: The memory battery is using Wechsler Memory Scale (Chinese), including Logical Memory I & II, Word Lists Ⅰ & II, Faces Ⅰ and spatial span.
measure: Changes of general cognitive function
time frame: From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete.
description: General cognitive function are tested using cognitive abilities screening instrument, CASI for screening and to test cognitive function as a whole.
measure: Changes of Quality of life
time frame: From baseline to 4 months after RT complete, the participants are requested to fill in the questionnaire of quality of life at baseline before radiotherapy begins, and 2 months after radiotherapy complete and 4 months after radiotherapy complete.
description: Quality of life are assessed using The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire
arm group label: HA-WBRT
arm group type: Other
description: Patients with brain metastases outside a 5-mm margin around either hippocampus and are eligible to this study will receive hippocampal avoidance whole brain radiotherapy 30 gray (Gy) in 10 fractions. The primary endpoint is Wechsler Memory Scale (Chinese) and cognitive abilities screening instrument (CASI) at 4 months.
intervention type: Radiation
intervention name: Hippocampal avoidance whole brain radiotherapy
description: Planning target volume(PTV) for whole brain is Whole brain parenchyma plus2mm margin excluding metastases and HA region, 30Gy in 10 fractions will be delivered to PTVwhole brain. Bilateral Hippocampus will be contoured according to Radiation Therapy Oncology Group 0933 and hippocampal avoidance region is Hippocampi + 5mm margin. According to Radiation Therapy Oncology Group 0933 trial, dose to 100% of the hippocampus could not exceed 9 Gy, and maximal hippocampal dose could not exceed 16 Gy; dose to 100% of the hippocampus exceeding 10 Gy
arm group label: HA-WBRT
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Pen-Tzu Fang, MD
role: Principal Investigator
affiliation: Department of Radiation Oncology, Kaohsiung Medical University Hospital
last name: Pen-Tzu Fang, MD
phone: 886-7-3121101
phone ext: 7158
email: ptmonicafang@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
citation: Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27.
PMID: 25349290
citation: Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95. doi: 10.1016/j.ijrobp.2007.03.048.
PMID: 17674975
citation: Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995 Feb 15;31(4):983-98. doi: 10.1016/0360-3016(94)00550-8.
PMID: 7860415
citation: DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.
PMID: 2725874
citation: Ghia A, Tome WA, Thomas S, Cannon G, Khuntia D, Kuo JS, Mehta MP. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):971-7. doi: 10.1016/j.ijrobp.2007.02.016. Epub 2007 Apr 18.
PMID: 17446005
citation: Gondi V, Tome WA, Marsh J, Struck A, Ghia A, Turian JV, Bentzen SM, Kuo JS, Khuntia D, Mehta MP. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933. Radiother Oncol. 2010 Jun;95(3):327-31. doi: 10.1016/j.radonc.2010.02.030. Epub 2010 Apr 12.
PMID: 20392503
citation: Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, Khuntia D, Tome WA. Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1244-52. doi: 10.1016/j.ijrobp.2010.01.039.
PMID: 20598457
citation: Gutierrez AN, Westerly DC, Tome WA, Jaradat HA, Mackie TR, Bentzen SM, Khuntia D, Mehta MP. Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):589-97. doi: 10.1016/j.ijrobp.2007.05.038.
PMID: 17869672
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No