<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/NCT01713699</url>
  </required_header>
  <id_info>
    <org_study_id>N12CLM</org_study_id>
    <nct_id>NCT01713699</nct_id>
  </id_info>
  <brief_title>Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases</brief_title>
  <official_title>Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Netherlands Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Netherlands Cancer Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether the quantitative detection of circulating&#xD;
      tumor cells (CTCs) in patients with Epcam expressing tumors can be used compared to standard&#xD;
      qualitative method - cytology both in the cerebrospinal fluid of patients, clinically&#xD;
      suspected for leptomeningeal metastases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Leptomeningeal metastases (LM), is a diffuse dissemination of tumor cells into the&#xD;
      cerebrospinal fluid (CSF) and leptomeninges.[1] Up to 8% of all patients with cancer develop&#xD;
      LM. Gadolinium enhanced MRI of the symptomatic location of the nervous system is the&#xD;
      radiological method of choice when LM is clinically suspected. In patients with a&#xD;
      metastasized tumor, based on clinical signs of LM and contrast enhancement of either the&#xD;
      leptomeninges, pia mater/cortex or cranial or spinal nerves on MRI, the diagnosis LM can be&#xD;
      made. The sensitivity of MRI with gadolineum for LM is 75% and the specificity 77%. If MRI&#xD;
      does not show equivocal abnormalities, CSF cytology needs to be performed. In 55% of patients&#xD;
      with LM from solid tumors, malignant cells are found during the first CSF examination. The&#xD;
      sensitivity raises to 80-90% after the second CSF sampling, as determined in the pre-MRI era.&#xD;
      The volume of sampled CSF determines partly the sensitivity of CSF cytology. If possible, 10&#xD;
      ml CSF needs to be taken and the material must be processed as quickly as possible.&#xD;
&#xD;
      Recently, Patel et al (2011) described the detection of breast cancer cells in the CSF using&#xD;
      the Cell Search System (Veridex). [6] Using this method, the CSF is enriched&#xD;
      immuno-magnetically for the epithelial cell adhesion molecule (EpCAM). Next nuclear staining&#xD;
      with 4 ',6-diamidino-2-phenylindole (DAPI) and immunofluorescent detection with cytokeratin&#xD;
      and CD45 is performed in 5 patients with leptomeningeal metastases from breast cancer and&#xD;
      approximately 104 circulating tumor cells (CTCs)in 7,5 ml CSF were found, using this method.&#xD;
      There seemed to be an association between the number of CTCs and response to intrathecal&#xD;
      administered chemotherapy in this small group of patients.&#xD;
&#xD;
      In the future, the determination of CTCs in the CSF could be a new quantitative method for&#xD;
      the anti-tumor response assessment of systemic or intrathecal therapy (as opposed to CSF&#xD;
      cytology, which is subjective and not a quantitative method). If the method shows greater&#xD;
      sensitivity than CSF cytology and can reliably measure single tumor cells, the sensitivity of&#xD;
      CSF examination in patients with a clinical suspicion of LM will increase. Possibly, this&#xD;
      method can also be used to detect micrometastases in the CSF in patients without neurological&#xD;
      symptoms, but with a high risk of CNS metastases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">September 19, 2017</completion_date>
  <primary_completion_date type="Actual">September 6, 2016</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>Determine the sensitivity and specificity of detection of circulating tumor cells (CTCs) in patients with Epcam expressing tumors compared to cytology in the cerebrospinal fluid of patients, clinically suspected for leptomeningeal metastases</measure>
    <time_frame>3 months after end of study</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>- To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To determine the relationships between demographics/tumor status and CTCs number in CSF.</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To compare the predictive value of two CTC enumeration methods</measure>
    <time_frame>3 months after end of study</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">146</enrollment>
  <condition>Meningeal Carcinomatosis</condition>
  <arm_group>
    <arm_group_label>diagnostic</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Using extra CSF material received by clinically indicated lumbar punctures to determine the sensitivity and specificity of CTCs in CSF (5ml CSF). Standard material of 5 ml CSF for cytology and 2 ml CSF for cell count and chemistry is being regularly used and processed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>lumbar puncture</intervention_name>
    <arm_group_label>diagnostic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are treated for advanced EpCam positive solid tumors (such as breast&#xD;
             cancer, lung cancer, gastrointestinal cancer)&#xD;
&#xD;
          -  Age &gt;= 18 years;&#xD;
&#xD;
          -  Able and willing to give written informed consent;&#xD;
&#xD;
          -  WHO performance status (0, 1, 2, 3 or 4);&#xD;
&#xD;
          -  Able and willing to undergo lumbar puncture and veni-puncture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lumbar puncture not clinically / diagnostically indicated&#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>D. Brandsma, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NKI-AvL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dutch Cancer Institute - Antoni van Leeuwenhoek</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Slotervaart Hospital</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066EC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://www.nki.nl/Research</url>
    <description>NKI-AVL</description>
  </link>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CTC, cytology, meningeal carcinomatosis, leptomeningeal metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplastic Cells, Circulating</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Meningeal Carcinomatosis</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/NCT01713699
org study id: N12CLM
nct id: NCT01713699
lead sponsor: 
has dmc: No
The purpose of this study is to determine whether the quantitative detection of circulating
      tumor cells (CTCs) in patients with Epcam expressing tumors can be used compared to standard
      qualitative method - cytology both in the cerebrospinal fluid of patients, clinically
      suspected for leptomeningeal metastases.
Leptomeningeal metastases (LM), is a diffuse dissemination of tumor cells into the
      cerebrospinal fluid (CSF) and leptomeninges.[1] Up to 8% of all patients with cancer develop
      LM. Gadolinium enhanced MRI of the symptomatic location of the nervous system is the
      radiological method of choice when LM is clinically suspected. In patients with a
      metastasized tumor, based on clinical signs of LM and contrast enhancement of either the
      leptomeninges, pia mater/cortex or cranial or spinal nerves on MRI, the diagnosis LM can be
      made. The sensitivity of MRI with gadolineum for LM is 75% and the specificity 77%. If MRI
      does not show equivocal abnormalities, CSF cytology needs to be performed. In 55% of patients
      with LM from solid tumors, malignant cells are found during the first CSF examination. The
      sensitivity raises to 80-90% after the second CSF sampling, as determined in the pre-MRI era.
      The volume of sampled CSF determines partly the sensitivity of CSF cytology. If possible, 10
      ml CSF needs to be taken and the material must be processed as quickly as possible.

      Recently, Patel et al (2011) described the detection of breast cancer cells in the CSF using
      the Cell Search System (Veridex). [6] Using this method, the CSF is enriched
      immuno-magnetically for the epithelial cell adhesion molecule (EpCAM). Next nuclear staining
      with 4 ',6-diamidino-2-phenylindole (DAPI) and immunofluorescent detection with cytokeratin
      and CD45 is performed in 5 patients with leptomeningeal metastases from breast cancer and
      approximately 104 circulating tumor cells (CTCs)in 7,5 ml CSF were found, using this method.
      There seemed to be an association between the number of CTCs and response to intrathecal
      administered chemotherapy in this small group of patients.

      In the future, the determination of CTCs in the CSF could be a new quantitative method for
      the anti-tumor response assessment of systemic or intrathecal therapy (as opposed to CSF
      cytology, which is subjective and not a quantitative method). If the method shows greater
      sensitivity than CSF cytology and can reliably measure single tumor cells, the sensitivity of
      CSF examination in patients with a clinical suspicion of LM will increase. Possibly, this
      method can also be used to detect micrometastases in the CSF in patients without neurological
      symptoms, but with a high risk of CNS metastases.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Determine the sensitivity and specificity of detection of circulating tumor cells (CTCs) in patients with Epcam expressing tumors compared to cytology in the cerebrospinal fluid of patients, clinically suspected for leptomeningeal metastases
time frame: 3 months after end of study
measure: - To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score
time frame: 3 months after end of study
measure: - To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy
time frame: 3 months after end of study
measure: - To determine the relationships between demographics/tumor status and CTCs number in CSF.
time frame: 3 months after end of study
measure: - To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood
time frame: 3 months after end of study
measure: To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.
time frame: 3 months after end of study
measure: - To compare the predictive value of two CTC enumeration methods
time frame: 3 months after end of study
arm group label: diagnostic
arm group type: Other
description: Using extra CSF material received by clinically indicated lumbar punctures to determine the sensitivity and specificity of CTCs in CSF (5ml CSF). Standard material of 5 ml CSF for cytology and 2 ml CSF for cell count and chemistry is being regularly used and processed.
intervention type: Procedure
intervention name: lumbar puncture
arm group label: diagnostic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: D. Brandsma, MD, PhD
role: Principal Investigator
affiliation: NKI-AvL
facility: 
facility: 
country: Netherlands
url: http://www.nki.nl/Research
description: NKI-AVL
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Neoplastic Cells, Circulating
mesh term: Carcinoma
mesh term: Meningeal Carcinomatosis