<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/NCT01727531</url>
  </required_header>
  <id_info>
    <org_study_id>R09-2775L</org_study_id>
    <nct_id>NCT01727531</nct_id>
  </id_info>
  <brief_title>IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine (CQ) in Brain Metastasis Radiotherapy</brief_title>
  <official_title>IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine in Brain Metastasis Radiotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Main Line Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Main Line Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research is being done to determine if a short course of Chloroquine (five weeks)&#xD;
      before, during and after whole brain radiation therapy (WBRT) will improve the overall&#xD;
      survival of subjects being treated for brain metastases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis one: A short course of chloroquine one week prior and four weeks after initiation&#xD;
      of WBRT is tolerable and significantly increases the median survival time of patients&#xD;
      suffering from brain metastasis as assessed one, three, six, nine, twelve and 24 months post&#xD;
      radiotherapy, when compared to historic controls.&#xD;
&#xD;
      Hypothesis two: The presence of one or both single-nucleotide polymorphisms (SNP)s in the&#xD;
      gene coding for the immunoregulatory enzyme indoleamine 2,3-dioxygenase 2 (IDO2) improves the&#xD;
      clinical outcomes of WBRT or the response to CQ co-treatment.&#xD;
&#xD;
      3.2. Specific Aims:&#xD;
&#xD;
      The specific aims of this study are:&#xD;
&#xD;
        1. Determine patients physical profiles prior WBRT and at regular intervals afterwards up&#xD;
           to 24 months after radiotherapy.&#xD;
&#xD;
        2. Record the status of patient metastases (i.e. number, location, size)&#xD;
&#xD;
        3. Determine patients' KPS values.&#xD;
&#xD;
        4. Record the incidence and causes of mortality of patients.&#xD;
&#xD;
        5. Determine the genotype of IDO2 for each patient.&#xD;
&#xD;
        6. Following data analysis, test the validity of the two hypotheses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2008</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</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>Specific Aim</measure>
    <time_frame>up to 24-months after completion of treatment</time_frame>
    <description>Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint: death</measure>
    <time_frame>up to 24 months after completion of treatment</time_frame>
    <description>from any cause</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Additional Aims</measure>
    <time_frame>up to 24 months after completion of treatment</time_frame>
    <description>Record the status of patient metastases (i.e. number, location, size)</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Aims</measure>
    <time_frame>up to 24 months after completion of treatment</time_frame>
    <description>Record KPS</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Aims</measure>
    <time_frame>up to 24 months after completion of treatment</time_frame>
    <description>Record genotype of IDO2</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Brain Metastasis</condition>
  <arm_group>
    <arm_group_label>CQ Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chloroquine diphosphate</intervention_name>
    <description>250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks</description>
    <arm_group_label>CQ Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically confirmed primary solid malignancy&#xD;
&#xD;
          -  Patients with single or multiple brain metastases&#xD;
&#xD;
          -  Patients with metastasis diameter &lt; 5 cm&#xD;
&#xD;
          -  Age &gt; 18&#xD;
&#xD;
          -  Clearance from the patient's physician that treatment with chloroquine should not pose&#xD;
             a problem to the patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of hypotension, cardiomyopathy, epilepsy, seizures&#xD;
&#xD;
          -  Patients with impaired renal function&#xD;
&#xD;
          -  Patients with psoriasis, porphyria&#xD;
&#xD;
          -  Patients with known hypersensitivity to 4-aminoquinoline compounds&#xD;
&#xD;
          -  Pregnancy, nursing&#xD;
&#xD;
          -  Prior radiotherapy&#xD;
&#xD;
          -  During the chloroquine treatment, patients complaining from visual or auditory&#xD;
             disturbances, and patients suffering from acute gastrointestinal problems i.e.&#xD;
             Anorexia, nausea, vomiting, diarrhea, abdominal cramps&#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>Albert DeNittis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Main Line Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lankenau Medical Center</name>
      <address>
        <city>Wynnewood</city>
        <state>Pennsylvania</state>
        <zip>19096</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <last_update_submitted>April 7, 2015</last_update_submitted>
  <last_update_submitted_qc>April 7, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Main Line Health</investigator_affiliation>
    <investigator_full_name>Albert DeNittis</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>chloroquine</keyword>
  <keyword>WBRT</keyword>
  <keyword>survival</keyword>
  <keyword>brain metastasis</keyword>
  <keyword>radiotherapy</keyword>
  <keyword>SNPs</keyword>
  <keyword>gene coding</keyword>
  <keyword>immunoregulatory enzyme IDO2</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chloroquine</mesh_term>
    <mesh_term>Chloroquine diphosphate</mesh_term>
  </intervention_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/NCT01727531
org study id: R09-2775L
nct id: NCT01727531
lead sponsor: 
has dmc: No
This research is being done to determine if a short course of Chloroquine (five weeks)
      before, during and after whole brain radiation therapy (WBRT) will improve the overall
      survival of subjects being treated for brain metastases.
Hypothesis one: A short course of chloroquine one week prior and four weeks after initiation
      of WBRT is tolerable and significantly increases the median survival time of patients
      suffering from brain metastasis as assessed one, three, six, nine, twelve and 24 months post
      radiotherapy, when compared to historic controls.

      Hypothesis two: The presence of one or both single-nucleotide polymorphisms (SNP)s in the
      gene coding for the immunoregulatory enzyme indoleamine 2,3-dioxygenase 2 (IDO2) improves the
      clinical outcomes of WBRT or the response to CQ co-treatment.

      3.2. Specific Aims:

      The specific aims of this study are:

        1. Determine patients physical profiles prior WBRT and at regular intervals afterwards up
           to 24 months after radiotherapy.

        2. Record the status of patient metastases (i.e. number, location, size)

        3. Determine patients' KPS values.

        4. Record the incidence and causes of mortality of patients.

        5. Determine the genotype of IDO2 for each patient.

        6. Following data analysis, test the validity of the two hypotheses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Specific Aim
time frame: up to 24-months after completion of treatment
description: Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy
measure: Secondary endpoint: death
time frame: up to 24 months after completion of treatment
description: from any cause
measure: Additional Aims
time frame: up to 24 months after completion of treatment
description: Record the status of patient metastases (i.e. number, location, size)
measure: Additional Aims
time frame: up to 24 months after completion of treatment
description: Record KPS
measure: Additional Aims
time frame: up to 24 months after completion of treatment
description: Record genotype of IDO2
arm group label: CQ Arm
arm group type: Experimental
description: 250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks.
intervention type: Drug
intervention name: Chloroquine diphosphate
description: 250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks
arm group label: CQ Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Albert DeNittis, MD
role: Principal Investigator
affiliation: Main Line Health
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Main Line Health
investigator full name: Albert DeNittis
investigator title: Principal Investigator
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Chloroquine
mesh term: Chloroquine diphosphate