xml: <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/NCT05984108</url>
    </required_header>
    <id_info>
      <org_study_id>2022PI132</org_study_id>
      <nct_id>NCT05984108</nct_id>
    </id_info>
    <brief_title>Clinical, Radiological, Histologic and Molecular Features of a Cohort of Melanocytic Tumors of the Central Nervous System</brief_title>
    <acronym>MelaMen</acronym>
    <official_title>Clinical, Radiological, Histological and Molecular Features of a Cohort of Melanocytic Tumors of the Central Nervous System</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Central Hospital, Nancy, France</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Central Hospital, Nancy, France</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>
        Primary melanocytic tumors of the central nervous system are rare lesions and occur develop&#xD;
        from leptomeningeal melanocytes. The WHO classification of tumors of the central nervous&#xD;
        system in its most recent version (2021) distinguishes on the one hand the circumscribed&#xD;
        melanocytic tumors including melanocytoma, benign, and its slope malignant, meningeal&#xD;
        melanoma, with an intermediate grade lesion in between, called intermediate grade&#xD;
        melanocytoma. They are to be distinguished from diffuse tumors or multifocal diseases such as&#xD;
        melanocytosis and its malignant corollary, melanomatosis. The main current challenge is to&#xD;
        distinguish them from their differential diagnoses, namely metastasis of a cutaneous or&#xD;
        extrac-cutaneous melanoma mainly and on the other hand other pigmented entities occuring in&#xD;
        the CNS such as malignant melanic tumor of the peripheral nerve sheath (MMNST, formerly&#xD;
        &quot;melanotic schwannoma&quot;).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The discovery within the CNS of a tumor of melanocytic nature requires the realization an&#xD;
        exhaustive assessment (dermatological examination, whole body imaging), especially in the&#xD;
        event of signs histological evidence of malignancy (marked atypia, mitoses, infiltration of&#xD;
        the parenchyma), in order to look for unnoticed cutaneous melanoma. In the absence of primary&#xD;
        lesion found outside the nervous system, the question of a primary lesion with a meningeal&#xD;
        starting point arises. A molecular characterization is then required, in order to highlight&#xD;
        mutations recurrent spores of the GNA11 or GNAQ genes, classically not found in the cutaneous&#xD;
        melanomas, the latter presenting different genetic alterations (BRAF, NRAS, KIT etc). Other&#xD;
        rarer alterations such as PLCB4 or CYSLTR2 are also described in these meningeal melanocytic&#xD;
        tumors, but are not part of the gene panels of routine. On the other hand, the discovery of a&#xD;
        circumscribed melanocytic lesion, in particular intradural extramedullary and spindle cells,&#xD;
        should suggest the differential diagnosis malignant melanotic nerve sheath tumor (MMNST,&#xD;
        malignant melanotic nerve sheath tumor), formerly called &quot;melanotic schwannoma&quot;. Distinguish&#xD;
        them histologically can be tricky. This differential diagnosis is important, the MMNST&#xD;
        entering often in the context of Carney syndrome, of autosomal dominant transmission,&#xD;
        responsible for other conditions requiring multidisciplinary follow-up (cardiac myxoma,&#xD;
        endocrine disorders). Recent advances in molecular biology have opened up new possibilities&#xD;
        for the diagnosis and classification of brain tumours. One of them is the methylome, studying&#xD;
        the epigenetic signature of a tumor via its methylation profile.&#xD;
  &#xD;
        These epigenetic modifications play an important role in regulating the expression genes and&#xD;
        are now well known to be involved in the development and cancer progression. This tool has&#xD;
        been integrated into the new WHO 2021 classification of CNS tumors and constitutes for&#xD;
        certain entities an essential criterion for their diagnosis final. The publication by Capper&#xD;
        et al. in 2018, entitled &quot;DNA methylation-based classification of central nervous system&#xD;
        tumours&quot; illustrates this point. It was highlighted that meningeal melanocytic tumors cluster&#xD;
        separately from other types of tumors, including cutaneous melanomas. Three methylation&#xD;
        classes exist currently in version 12.5 of the classifier developed by the University of&#xD;
        Heidelberg (www.molecularneuropathology.com): a class of methylation specific to the&#xD;
        metastases of melanoma, one for malignant melanotic peripheral nerve sheath tumors, and a&#xD;
        titled melanocytoma (which includes entities with similar profiles: melanocytoma and&#xD;
        meningeal melanoma but also uveal melanoma). He does not exist to date of methylation class&#xD;
        for diffuse meningeal melanocytic tumors(melanocytosis and its malignant corollary&#xD;
        melanomatosis).&#xD;
  &#xD;
        To conclude, meningeal melanocytic tumors are a group of tumors of the system central nervous&#xD;
        system rare but for which it is necessary to make a diagnosis of certainty The WHO&#xD;
        classification proposed in 2021 is based on an integrative histo-molecular approach, but for&#xD;
        which the community medicine still lacks perspective. In particular, when using this new&#xD;
        classification, it there are difficulties in classifying certain tumours, presenting clinical&#xD;
        aspects, discordant radiological, histopathological and molecular findings.&#xD;
  &#xD;
        The aims of this study are therefore to classify melanocytic tumors according to the new WHO&#xD;
        2021 classification of central nervous system tumors, to describe their clinical,&#xD;
        radiological, histological and molecular characteristics, to define new prognostic criteria&#xD;
        (mitotic index, Ki-67 , immunohistochemical markers such as BAP1 and p16) and to establish&#xD;
        clinico-radio-histo-molecular correlations.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2023</start_date>
    <completion_date type="Anticipated">June 2024</completion_date>
    <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Diagnosis according to WHO classification of CNS tumors (5th edition)</measure>
      <time_frame>at baseline (initial report)</time_frame>
      <description>Histologic diagnosis according to WHO classification of CNS tumors (5th edition) among these 5 options : melanocytoma, intermediate-grade melanocytoma, melanoma, melanocytosis, melanomatosis</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mitotic index</measure>
      <time_frame>at baseline (initial report)</time_frame>
      <description>Number of mitoses per square millimetre</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Age</measure>
      <time_frame>At baseline</time_frame>
      <description>Age in years</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Sex</measure>
      <time_frame>At baseline</time_frame>
      <description>Male or female</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Ki-67</measure>
      <time_frame>At time of initial diagnosis</time_frame>
      <description>Proliferation index Ki-67, assessed by immunohistochemistry, counted on 500 cells</description>
    </primary_outcome>
    <primary_outcome>
      <measure>T1-weighted sequence signal</measure>
      <time_frame>At time of initial diagnosis</time_frame>
      <description>Radiologic feature : tumor T1-weighted sequence signal on MRI (hyposignal, isosignal, hypersignal)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Enhancement after gadolinium injection</measure>
      <time_frame>At time of initial diagnosis</time_frame>
      <description>Radiologic feature: tumor enhancement after gadolinium injection on MRI</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From date of initial diagnosis until the date of death of any cause assessed up to 10 years</time_frame>
      <description>Time from diagnosis to death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>From date of initial diagnosis until the date of first documented progression assessed up to 10 years</time_frame>
      <description>Time from diagnosis to first progression</description>
    </secondary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Meningeal Melanocytoma</condition>
    <condition>Meningeal Melanomatosis</condition>
    <condition>Meningeal Melanocytosis</condition>
    <condition>Meningeal Melanoma</condition>
    <arm_group>
      <arm_group_label>Meningeal melanocytoma</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Meningeal melanoma</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Meningeal melanomatosis</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Meningeal melanocytosis</arm_group_label>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Formalin-fixed Paraffin-embedded tumor samples&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with primitive meningeal melanocytic tumors&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patient with a primitive meningeal melanocytic tumor&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient with metastatic extrameningeal melanoma&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Nancy University Hospital Center</name>
        <address>
          <city>Nancy</city>
          <zip>54500</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Guillaume GAUCHOTTE, PhD</last_name>
        <phone>+33 3 83 65 60 17</phone>
        <email>g.gauchotte@chru-nancy.fr</email>
      </contact>
      <contact_backup>
        <last_name>Emilie BECKER, MD</last_name>
        <phone>+33 3 83 65 60 17</phone>
        <email>e.becker@chru-nancy.fr</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <reference>
      <citation>Koelsche C, Hovestadt V, Jones DT, Capper D, Sturm D, Sahm F, Schrimpf D, Adeberg S, Bohmer K, Hagenlocher C, Mechtersheimer G, Kohlhof P, Muhleisen H, Beschorner R, Hartmann C, Braczynski AK, Mittelbronn M, Buslei R, Becker A, Grote A, Urbach H, Staszewski O, Prinz M, Hewer E, Pfister SM, von Deimling A, Reuss DE. Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol. 2015 Mar;25(2):202-8. doi: 10.1111/bpa.12228. Epub 2014 Dec 15.</citation>
      <PMID>25399693</PMID>
    </reference>
    <reference>
      <citation>Kusters-Vandevelde HV, Kusters B, van Engen-van Grunsven AC, Groenen PJ, Wesseling P, Blokx WA. Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects. Brain Pathol. 2015 Mar;25(2):209-26. doi: 10.1111/bpa.12241.</citation>
      <PMID>25534128</PMID>
    </reference>
    <reference>
      <citation>Griewank KG, Koelsche C, van de Nes JAP, Schrimpf D, Gessi M, Moller I, Sucker A, Scolyer RA, Buckland ME, Murali R, Pietsch T, von Deimling A, Schadendorf D. Integrated Genomic Classification of Melanocytic Tumors of the Central Nervous System Using Mutation Analysis, Copy Number Alterations, and DNA Methylation Profiling. Clin Cancer Res. 2018 Sep 15;24(18):4494-4504. doi: 10.1158/1078-0432.CCR-18-0763. Epub 2018 Jun 11.</citation>
      <PMID>29891723</PMID>
    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Central Hospital, Nancy, France</investigator_affiliation>
      <investigator_full_name>Guillaume GAUCHOTTE</investigator_full_name>
      <investigator_title>PhD</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Central Nervous System Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984108
  org study id: 2022PI132
  nct id: NCT05984108
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Primary melanocytic tumors of the central nervous system are rare lesions and occur develop
        from leptomeningeal melanocytes. The WHO classification of tumors of the central nervous
        system in its most recent version (2021) distinguishes on the one hand the circumscribed
        melanocytic tumors including melanocytoma, benign, and its slope malignant, meningeal
        melanoma, with an intermediate grade lesion in between, called intermediate grade
        melanocytoma. They are to be distinguished from diffuse tumors or multifocal diseases such as
        melanocytosis and its malignant corollary, melanomatosis. The main current challenge is to
        distinguish them from their differential diagnoses, namely metastasis of a cutaneous or
        extrac-cutaneous melanoma mainly and on the other hand other pigmented entities occuring in
        the CNS such as malignant melanic tumor of the peripheral nerve sheath (MMNST, formerly
        "melanotic schwannoma").
  The discovery within the CNS of a tumor of melanocytic nature requires the realization an
        exhaustive assessment (dermatological examination, whole body imaging), especially in the
        event of signs histological evidence of malignancy (marked atypia, mitoses, infiltration of
        the parenchyma), in order to look for unnoticed cutaneous melanoma. In the absence of primary
        lesion found outside the nervous system, the question of a primary lesion with a meningeal
        starting point arises. A molecular characterization is then required, in order to highlight
        mutations recurrent spores of the GNA11 or GNAQ genes, classically not found in the cutaneous
        melanomas, the latter presenting different genetic alterations (BRAF, NRAS, KIT etc). Other
        rarer alterations such as PLCB4 or CYSLTR2 are also described in these meningeal melanocytic
        tumors, but are not part of the gene panels of routine. On the other hand, the discovery of a
        circumscribed melanocytic lesion, in particular intradural extramedullary and spindle cells,
        should suggest the differential diagnosis malignant melanotic nerve sheath tumor (MMNST,
        malignant melanotic nerve sheath tumor), formerly called "melanotic schwannoma". Distinguish
        them histologically can be tricky. This differential diagnosis is important, the MMNST
        entering often in the context of Carney syndrome, of autosomal dominant transmission,
        responsible for other conditions requiring multidisciplinary follow-up (cardiac myxoma,
        endocrine disorders). Recent advances in molecular biology have opened up new possibilities
        for the diagnosis and classification of brain tumours. One of them is the methylome, studying
        the epigenetic signature of a tumor via its methylation profile.
  
        These epigenetic modifications play an important role in regulating the expression genes and
        are now well known to be involved in the development and cancer progression. This tool has
        been integrated into the new WHO 2021 classification of CNS tumors and constitutes for
        certain entities an essential criterion for their diagnosis final. The publication by Capper
        et al. in 2018, entitled "DNA methylation-based classification of central nervous system
        tumours" illustrates this point. It was highlighted that meningeal melanocytic tumors cluster
        separately from other types of tumors, including cutaneous melanomas. Three methylation
        classes exist currently in version 12.5 of the classifier developed by the University of
        Heidelberg (www.molecularneuropathology.com): a class of methylation specific to the
        metastases of melanoma, one for malignant melanotic peripheral nerve sheath tumors, and a
        titled melanocytoma (which includes entities with similar profiles: melanocytoma and
        meningeal melanoma but also uveal melanoma). He does not exist to date of methylation class
        for diffuse meningeal melanocytic tumors(melanocytosis and its malignant corollary
        melanomatosis).
  
        To conclude, meningeal melanocytic tumors are a group of tumors of the system central nervous
        system rare but for which it is necessary to make a diagnosis of certainty The WHO
        classification proposed in 2021 is based on an integrative histo-molecular approach, but for
        which the community medicine still lacks perspective. In particular, when using this new
        classification, it there are difficulties in classifying certain tumours, presenting clinical
        aspects, discordant radiological, histopathological and molecular findings.
  
        The aims of this study are therefore to classify melanocytic tumors according to the new WHO
        2021 classification of central nervous system tumors, to describe their clinical,
        radiological, histological and molecular characteristics, to define new prognostic criteria
        (mitotic index, Ki-67 , immunohistochemical markers such as BAP1 and p16) and to establish
        clinico-radio-histo-molecular correlations.
  observational model: Cohort
  time perspective: Retrospective
  measure: Diagnosis according to WHO classification of CNS tumors (5th edition)
  time frame: at baseline (initial report)
  description: Histologic diagnosis according to WHO classification of CNS tumors (5th edition) among these 5 options : melanocytoma, intermediate-grade melanocytoma, melanoma, melanocytosis, melanomatosis
  measure: Mitotic index
  time frame: at baseline (initial report)
  description: Number of mitoses per square millimetre
  measure: Age
  time frame: At baseline
  description: Age in years
  measure: Sex
  time frame: At baseline
  description: Male or female
  measure: Ki-67
  time frame: At time of initial diagnosis
  description: Proliferation index Ki-67, assessed by immunohistochemistry, counted on 500 cells
  measure: T1-weighted sequence signal
  time frame: At time of initial diagnosis
  description: Radiologic feature : tumor T1-weighted sequence signal on MRI (hyposignal, isosignal, hypersignal)
  measure: Enhancement after gadolinium injection
  time frame: At time of initial diagnosis
  description: Radiologic feature: tumor enhancement after gadolinium injection on MRI
  measure: Overall survival
  time frame: From date of initial diagnosis until the date of death of any cause assessed up to 10 years
  description: Time from diagnosis to death
  measure: Progression-free survival
  time frame: From date of initial diagnosis until the date of first documented progression assessed up to 10 years
  description: Time from diagnosis to first progression
  arm group label: Meningeal melanocytoma
  arm group label: Meningeal melanoma
  arm group label: Meningeal melanomatosis
  arm group label: Meningeal melanocytosis
  Formalin-fixed Paraffin-embedded tumor samples
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: France
  citation: Koelsche C, Hovestadt V, Jones DT, Capper D, Sturm D, Sahm F, Schrimpf D, Adeberg S, Bohmer K, Hagenlocher C, Mechtersheimer G, Kohlhof P, Muhleisen H, Beschorner R, Hartmann C, Braczynski AK, Mittelbronn M, Buslei R, Becker A, Grote A, Urbach H, Staszewski O, Prinz M, Hewer E, Pfister SM, von Deimling A, Reuss DE. Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol. 2015 Mar;25(2):202-8. doi: 10.1111/bpa.12228. Epub 2014 Dec 15.
  PMID: 25399693
  citation: Kusters-Vandevelde HV, Kusters B, van Engen-van Grunsven AC, Groenen PJ, Wesseling P, Blokx WA. Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects. Brain Pathol. 2015 Mar;25(2):209-26. doi: 10.1111/bpa.12241.
  PMID: 25534128
  citation: Griewank KG, Koelsche C, van de Nes JAP, Schrimpf D, Gessi M, Moller I, Sucker A, Scolyer RA, Buckland ME, Murali R, Pietsch T, von Deimling A, Schadendorf D. Integrated Genomic Classification of Melanocytic Tumors of the Central Nervous System Using Mutation Analysis, Copy Number Alterations, and DNA Methylation Profiling. Clin Cancer Res. 2018 Sep 15;24(18):4494-4504. doi: 10.1158/1078-0432.CCR-18-0763. Epub 2018 Jun 11.
  PMID: 29891723
  responsible party type: Principal Investigator
  investigator affiliation: Central Hospital, Nancy, France
  investigator full name: Guillaume GAUCHOTTE
  investigator title: PhD
  mesh term: Central Nervous System Neoplasms
  sharing ipd: Undecided