<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/NCT03820778</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00010431</org_study_id>
    <nct_id>NCT03820778</nct_id>
  </id_info>
  <brief_title>Whole Body MRI to Identify Atypical Neurofibromas in Patients With NF1</brief_title>
  <official_title>Whole Body MRI to Identify Atypical Neurofibromas in Patients With NF1 and High Plexiform Neurofibroma Tumor Burden</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's National Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's National Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being conducted to determine if Whole Body MRI (WBMRI) can be used to identify&#xD;
      Atypical Neurofibromas (ANF) in Neurofibromatosis Type 1 (NF1) patients with high tumor&#xD;
      burden. Each enrolled participant will have two (2) WBMRIs without sedation during the study&#xD;
      period. Eligible participants must be Male or Female between the ages of 8-30 with diagnosed&#xD;
      NF1; with one or more PN greater than 3cm in diameter and willing to comply with study&#xD;
      procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study to determine the feasibility of using Whole Body MRI (WBMRI) to detect&#xD;
      Atypical Plexiform Neurofibromas (ANF) among Neurofibromatosis Type 1 (NF1) patients who are&#xD;
      at highest risk for developing these tumors. In order to do this, the investigators will&#xD;
      prospectively obtain WBMRI scans on patients with high plexiform tumor burden (which&#xD;
      investigators will define as &gt;=1 plexiform neurofibroma (PN) that is &gt;3cm in diameter on MRI)&#xD;
      at the same time as their regularly scheduled MRI to allow for radiographic comparison of the&#xD;
      identified PNs. In this study, the investigators will plan to establish a method that&#xD;
      effectively characterizes PNs in terms of their volume, radiographic appearance on WBMRI and&#xD;
      association with clinical characteristics.&#xD;
&#xD;
      As an exploratory aim, the investigators plan to collect blood samples from each patient at&#xD;
      the same time as the MRI to determine the feasibility of isolating cfDNA (circulating free&#xD;
      DNA) from plasma of patients with high plexiform tumor burden.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 12, 2018</start_date>
  <completion_date type="Anticipated">August 1, 2022</completion_date>
  <primary_completion_date type="Actual">August 1, 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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine if WBMRI can be used to identify ANF in NF1 patients with high tumor burden.</measure>
    <time_frame>2-3 years</time_frame>
    <description>Number of NF1 participants with high tumor burden who have ANF on WBMRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine if clinical signs and symptoms correlate with tumor burden and/or the presence of ANF on WBMRI</measure>
    <time_frame>2-3 years</time_frame>
    <description>Number of patients with high PN tumor burden who have clinical symptoms</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Determine if the cfDNA levels correlate with presence of ANF.</measure>
    <time_frame>3-4 years</time_frame>
    <description>Level of cfDNA in plasma of participants with ANF compared to participants without ANF</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Neurofibromatosis 1</condition>
  <condition>Neurofibroma</condition>
  <condition>Atypical Neurofibroma</condition>
  <condition>Atypical Neurofibromatosis</condition>
  <condition>Plexiform Neurofibroma</condition>
  <condition>Von Recklinghausen Disease</condition>
  <arm_group>
    <arm_group_label>Study Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Whole Body MRI along with standard of care regional MRI and blood draw at enrollment followed by Whole Body MRI along with standard of care regional MRI and blood draw after 4-6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Whole Body MRI</intervention_name>
    <description>WBMRI with axial and coronal STIR (short inversion time inversion recovery) images + DWI (diffuse weighted imaging) will be performed and compared to regional MRI to assess value of this diagnostic test for the identification of suspicious looking lesions (i.e. diffuse nodular lesions or atypical plexiform neurofibroma)</description>
    <arm_group_label>Study Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females between 8-30 years of age&#xD;
&#xD;
          2. Confirmed diagnosis of NF1&#xD;
&#xD;
          3. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          4. Prior MRI documentation confirming &gt;=1 PN that is &gt;3cm in diameter&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to undergo MRI without sedation&#xD;
&#xD;
          2. Presence of metal or other devices that are contraindicated for MRI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miriam Bornhorst, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's National Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's National Health System</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Nguyen R, Dombi E, Widemann BC, Solomon J, Fuensterer C, Kluwe L, Friedman JM, Mautner VF. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012 Oct 4;7:75. doi: 10.1186/1750-1172-7-75.</citation>
    <PMID>23035791</PMID>
  </reference>
  <reference>
    <citation>Kim A, Stewart DR, Reilly KM, Viskochil D, Miettinen MM, Widemann BC. Malignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies. Sarcoma. 2017;2017:7429697. doi: 10.1155/2017/7429697. Epub 2017 May 16.</citation>
    <PMID>28592921</PMID>
  </reference>
  <reference>
    <citation>Higham CS, Dombi E, Rogiers A, Bhaumik S, Pans S, Connor SEJ, Miettinen M, Sciot R, Tirabosco R, Brems H, Baldwin A, Legius E, Widemann BC, Ferner RE. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. 2018 May 18;20(6):818-825. doi: 10.1093/neuonc/noy013.</citation>
    <PMID>29409029</PMID>
  </reference>
  <reference>
    <citation>Beert E, Brems H, Daniels B, De Wever I, Van Calenbergh F, Schoenaers J, Debiec-Rychter M, Gevaert O, De Raedt T, Van Den Bruel A, de Ravel T, Cichowski K, Kluwe L, Mautner V, Sciot R, Legius E. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer. 2011 Dec;50(12):1021-32. doi: 10.1002/gcc.20921. Epub 2011 Aug 24.</citation>
    <PMID>21987445</PMID>
  </reference>
  <reference>
    <citation>Mautner VF, Asuagbor FA, Dombi E, Funsterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008 Aug;10(4):593-8. doi: 10.1215/15228517-2008-011. Epub 2008 Jun 17.</citation>
    <PMID>18559970</PMID>
  </reference>
  <reference>
    <citation>Dominguez-Vigil IG, Moreno-Martinez AK, Wang JY, Roehrl MHA, Barrera-Saldana HA. The dawn of the liquid biopsy in the fight against cancer. Oncotarget. 2017 Dec 8;9(2):2912-2922. doi: 10.18632/oncotarget.23131. eCollection 2018 Jan 5.</citation>
    <PMID>29416824</PMID>
  </reference>
  <reference>
    <citation>Plotkin SR, Bredella MA, Cai W, Kassarjian A, Harris GJ, Esparza S, Merker VL, Munn LL, Muzikansky A, Askenazi M, Nguyen R, Wenzel R, Mautner VF. Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis. PLoS One. 2012;7(4):e35711. doi: 10.1371/journal.pone.0035711. Epub 2012 Apr 27.</citation>
    <PMID>22558206</PMID>
  </reference>
  <reference>
    <citation>Ahlawat S, Fayad LM, Khan MS, Bredella MA, Harris GJ, Evans DG, Farschtschi S, Jacobs MA, Chhabra A, Salamon JM, Wenzel R, Mautner VF, Dombi E, Cai W, Plotkin SR, Blakeley JO; Whole Body MRI Committee for the REiNS International Collaboration; REiNS International Collaboration Members 2016. Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis. Neurology. 2016 Aug 16;87(7 Suppl 1):S31-9. doi: 10.1212/WNL.0000000000002929.</citation>
    <PMID>27527647</PMID>
  </reference>
  <reference>
    <citation>Cai W, Kassarjian A, Bredella MA, Harris GJ, Yoshida H, Mautner VF, Wenzel R, Plotkin SR. Tumor burden in patients with neurofibromatosis types 1 and 2 and schwannomatosis: determination on whole-body MR images. Radiology. 2009 Mar;250(3):665-73. doi: 10.1148/radiol.2503080700.</citation>
    <PMID>19244040</PMID>
  </reference>
  <reference>
    <citation>Wasa J, Nishida Y, Tsukushi S, Shido Y, Sugiura H, Nakashima H, Ishiguro N. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol. 2010 Jun;194(6):1568-74. doi: 10.2214/AJR.09.2724.</citation>
    <PMID>20489098</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's National Research Institute</investigator_affiliation>
    <investigator_full_name>Miriam Bornhorst</investigator_full_name>
    <investigator_title>Assistant Professor Division of Oncology and Center for Genetics Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurofibromatoses</mesh_term>
    <mesh_term>Neurofibromatosis 1</mesh_term>
    <mesh_term>Neurofibroma</mesh_term>
    <mesh_term>Neurofibroma, Plexiform</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>October 30, 2021</submitted>
    <returned>November 29, 2021</returned>
    <submitted>July 23, 2022</submitted>
    <returned>August 16, 2022</returned>
  </pending_results>
  <!-- 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/NCT03820778
org study id: Pro00010431
nct id: NCT03820778
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This study is being conducted to determine if Whole Body MRI (WBMRI) can be used to identify
      Atypical Neurofibromas (ANF) in Neurofibromatosis Type 1 (NF1) patients with high tumor
      burden. Each enrolled participant will have two (2) WBMRIs without sedation during the study
      period. Eligible participants must be Male or Female between the ages of 8-30 with diagnosed
      NF1; with one or more PN greater than 3cm in diameter and willing to comply with study
      procedures.
This is a study to determine the feasibility of using Whole Body MRI (WBMRI) to detect
      Atypical Plexiform Neurofibromas (ANF) among Neurofibromatosis Type 1 (NF1) patients who are
      at highest risk for developing these tumors. In order to do this, the investigators will
      prospectively obtain WBMRI scans on patients with high plexiform tumor burden (which
      investigators will define as >=1 plexiform neurofibroma (PN) that is >3cm in diameter on MRI)
      at the same time as their regularly scheduled MRI to allow for radiographic comparison of the
      identified PNs. In this study, the investigators will plan to establish a method that
      effectively characterizes PNs in terms of their volume, radiographic appearance on WBMRI and
      association with clinical characteristics.

      As an exploratory aim, the investigators plan to collect blood samples from each patient at
      the same time as the MRI to determine the feasibility of isolating cfDNA (circulating free
      DNA) from plasma of patients with high plexiform tumor burden.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: To determine if WBMRI can be used to identify ANF in NF1 patients with high tumor burden.
time frame: 2-3 years
description: Number of NF1 participants with high tumor burden who have ANF on WBMRI
measure: Determine if clinical signs and symptoms correlate with tumor burden and/or the presence of ANF on WBMRI
time frame: 2-3 years
description: Number of patients with high PN tumor burden who have clinical symptoms
measure: Determine if the cfDNA levels correlate with presence of ANF.
time frame: 3-4 years
description: Level of cfDNA in plasma of participants with ANF compared to participants without ANF
arm group label: Study Arm
arm group type: Experimental
description: Whole Body MRI along with standard of care regional MRI and blood draw at enrollment followed by Whole Body MRI along with standard of care regional MRI and blood draw after 4-6 months.
intervention type: Diagnostic Test
intervention name: Whole Body MRI
description: WBMRI with axial and coronal STIR (short inversion time inversion recovery) images + DWI (diffuse weighted imaging) will be performed and compared to regional MRI to assess value of this diagnostic test for the identification of suspicious looking lesions (i.e. diffuse nodular lesions or atypical plexiform neurofibroma)
arm group label: Study Arm
criteria: 
gender: All
minimum age: 8 Years
maximum age: 30 Years
healthy volunteers: No
last name: Miriam Bornhorst, MD
role: Principal Investigator
affiliation: Children's National Health System
facility: 
country: United States
citation: Nguyen R, Dombi E, Widemann BC, Solomon J, Fuensterer C, Kluwe L, Friedman JM, Mautner VF. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012 Oct 4;7:75. doi: 10.1186/1750-1172-7-75.
PMID: 23035791
citation: Kim A, Stewart DR, Reilly KM, Viskochil D, Miettinen MM, Widemann BC. Malignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies. Sarcoma. 2017;2017:7429697. doi: 10.1155/2017/7429697. Epub 2017 May 16.
PMID: 28592921
citation: Higham CS, Dombi E, Rogiers A, Bhaumik S, Pans S, Connor SEJ, Miettinen M, Sciot R, Tirabosco R, Brems H, Baldwin A, Legius E, Widemann BC, Ferner RE. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. 2018 May 18;20(6):818-825. doi: 10.1093/neuonc/noy013.
PMID: 29409029
citation: Beert E, Brems H, Daniels B, De Wever I, Van Calenbergh F, Schoenaers J, Debiec-Rychter M, Gevaert O, De Raedt T, Van Den Bruel A, de Ravel T, Cichowski K, Kluwe L, Mautner V, Sciot R, Legius E. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer. 2011 Dec;50(12):1021-32. doi: 10.1002/gcc.20921. Epub 2011 Aug 24.
PMID: 21987445
citation: Mautner VF, Asuagbor FA, Dombi E, Funsterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008 Aug;10(4):593-8. doi: 10.1215/15228517-2008-011. Epub 2008 Jun 17.
PMID: 18559970
citation: Dominguez-Vigil IG, Moreno-Martinez AK, Wang JY, Roehrl MHA, Barrera-Saldana HA. The dawn of the liquid biopsy in the fight against cancer. Oncotarget. 2017 Dec 8;9(2):2912-2922. doi: 10.18632/oncotarget.23131. eCollection 2018 Jan 5.
PMID: 29416824
citation: Plotkin SR, Bredella MA, Cai W, Kassarjian A, Harris GJ, Esparza S, Merker VL, Munn LL, Muzikansky A, Askenazi M, Nguyen R, Wenzel R, Mautner VF. Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis. PLoS One. 2012;7(4):e35711. doi: 10.1371/journal.pone.0035711. Epub 2012 Apr 27.
PMID: 22558206
citation: Ahlawat S, Fayad LM, Khan MS, Bredella MA, Harris GJ, Evans DG, Farschtschi S, Jacobs MA, Chhabra A, Salamon JM, Wenzel R, Mautner VF, Dombi E, Cai W, Plotkin SR, Blakeley JO; Whole Body MRI Committee for the REiNS International Collaboration; REiNS International Collaboration Members 2016. Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis. Neurology. 2016 Aug 16;87(7 Suppl 1):S31-9. doi: 10.1212/WNL.0000000000002929.
PMID: 27527647
citation: Cai W, Kassarjian A, Bredella MA, Harris GJ, Yoshida H, Mautner VF, Wenzel R, Plotkin SR. Tumor burden in patients with neurofibromatosis types 1 and 2 and schwannomatosis: determination on whole-body MR images. Radiology. 2009 Mar;250(3):665-73. doi: 10.1148/radiol.2503080700.
PMID: 19244040
citation: Wasa J, Nishida Y, Tsukushi S, Shido Y, Sugiura H, Nakashima H, Ishiguro N. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol. 2010 Jun;194(6):1568-74. doi: 10.2214/AJR.09.2724.
PMID: 20489098
responsible party type: Principal Investigator
investigator affiliation: Children's National Research Institute
investigator full name: Miriam Bornhorst
investigator title: Assistant Professor Division of Oncology and Center for Genetics Medicine
mesh term: Neurofibromatoses
mesh term: Neurofibromatosis 1
mesh term: Neurofibroma
mesh term: Neurofibroma, Plexiform
sharing ipd: No
submitted: October 30, 2021
returned: November 29, 2021
submitted: July 23, 2022
returned: August 16, 2022