<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/NCT02232243</url>
  </required_header>
  <id_info>
    <org_study_id>14-MULTI-14-MCC</org_study_id>
    <nct_id>NCT02232243</nct_id>
  </id_info>
  <brief_title>HCQ on PAR-4 Levels in Patients With Resectable Solid Tumors</brief_title>
  <official_title>A Pilot Study to Determine the Biological Effects of Hydroxychloroquine on PAR-4 Levels in Patients With Resectable Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peng Wang, MD PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Baseline levels of PAR-4 secreted by normal cells are generally inadequate to cause massive&#xD;
      apoptosis in cancer cells and drugs that bolster the secretion of PAR-4 would constitute an&#xD;
      important therapeutic advance.The apoptosis sensitizing features of hydroxychloroquine&#xD;
      enhance the anti-tumor effects of a broad range of cancer therapeutics. The investigators&#xD;
      hypothesize that hydroxychloroquine will induce at least 2-fold increase in systemic (plasma)&#xD;
      PAR-4 levels compared to pre-treatment plasma levels in patients with resectable solid&#xD;
      tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2015</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">January 1, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patients With Elevated Par-4 Levels</measure>
    <time_frame>Baseline and day 14</time_frame>
    <description>Number of patients with 2-fold change in Par-4 levels from baseline to day 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Optimal Biologic Dose of Hydroxychloroquine</measure>
    <time_frame>Day 14</time_frame>
    <description>Dose (mg twice daily) wherein 70% of patients exhibit a 2-fold increase in Par-4 levels with a dose-limiting toxicity of no more than 30%.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Initial: Hydroxychloroquine 400mg HCQ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>These initial 3 patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Secondary: Hydroxychloroquine 800mg HCQ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Based on data analysis from the initial patients, these patients received 400mg hydroxychloroquine (HCQ) twice daily (800mg/day total) for 14 days prior to surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tertiary: Hydroxychloroquine 400mg HCQ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Based on data from the primary and secondary groups, patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine, 200mg twice dailiy</intervention_name>
    <description>Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.</description>
    <arm_group_label>Initial: Hydroxychloroquine 400mg HCQ</arm_group_label>
    <arm_group_label>Tertiary: Hydroxychloroquine 400mg HCQ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine, 400mg twice daily</intervention_name>
    <description>Hydroxychloroquine, 400mg twice daily (800mg/day total) was given to subjects for up to 14 days prior to surgery.</description>
    <arm_group_label>Secondary: Hydroxychloroquine 800mg HCQ</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a histologically confirmed solid tumor that is planned for surgical&#xD;
             resection.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).&#xD;
&#xD;
          -  Patients must be able to ingest oral medications.&#xD;
&#xD;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count ≥1,500/mcL&#xD;
&#xD;
               -  platelets ≥100,000/mcL&#xD;
&#xD;
               -  total bilirubin Less than 1.5 x ULN&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal&#xD;
&#xD;
               -  Creatinine within normal institutional limits OR Creatinine clearance ≥60&#xD;
                  mL/min/1.73 m2 for patients with creatinine levels above institutional normal.&#xD;
&#xD;
          -  Patients must be able to undergo surgical resection of their tumor as determined by&#xD;
             the treating surgeon.&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with metastatic cancer and/or cancer that is not amenable to surgery.&#xD;
&#xD;
          -  Patients with significant malabsorption as determined by the treating physician.&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  Patients with known brain metastases are excluded from this clinical trial because of&#xD;
             their poor prognosis and because they often develop progressive neurologic dysfunction&#xD;
             that would confound the evaluation of neurologic and other adverse events. Patients&#xD;
             with primary brain tumors amenable to surgery are allowed on this protocol.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to hydroxychloroquine.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Pregnant women are excluded from this study.&#xD;
&#xD;
          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of&#xD;
             the potential for pharmacokinetic interactions with hydroxychloroquine. In addition,&#xD;
             these patients are at increased risk of lethal infections when treated with&#xD;
             marrow-suppressive therapy.&#xD;
&#xD;
          -  Patients that are on enzyme-inducing anti-epileptic medications&#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>Peng Wang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lucille P. Markey Cancer Center at University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky, Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Wang P, Burikhanov R, Jayswal R, Weiss HL, Arnold SM, Villano JL, Rangnekar VM. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018 May;9(5-6):190-197. doi: 10.18632/genesandcancer.181.</citation>
    <PMID>30603055</PMID>
  </results_reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <results_first_submitted>May 21, 2019</results_first_submitted>
  <results_first_submitted_qc>May 21, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 23, 2019</results_first_posted>
  <last_update_submitted>June 3, 2021</last_update_submitted>
  <last_update_submitted_qc>June 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Peng Wang, MD PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Surgery</keyword>
  <keyword>Hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 20, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02232243/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02232243/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was initiated July 2015 at the University of Kentucky and enrolled 10 adult patients with early stage solid malignancies.</recruitment_details>
      <pre_assignment_details>10 patients enrolled in this dose escalation study. In Period 1, three patients were assigned to receive 200mg HCQ twice daily. Based on toxicity and PAR-4 levels, in Period 2 the next four patients received 400mg HCQ twice daily. Following additional analysis, in Period 3 the final three patients received 200mg HCQ twice daily.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Initial: Hydroxychloroquine 400mg HCQ</title>
          <description>These patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.</description>
        </group>
        <group group_id="P2">
          <title>Secondary: Hydroxychloroquine 800mg HCQ</title>
          <description>These patients received 400mg hydroxychloroquine (HCQ) twice daily (800mg/day total) for 14 days prior to surgery.</description>
        </group>
        <group group_id="P3">
          <title>Tertiary: Hydroxychloroquine 400mg HCQ</title>
          <description>Based on data from primary and secondary groups, these patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Dose (200mg HCQ Twice Daily)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Dose (400mg HCQ Twice Daily)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Third Dose(200mg HCQ Twice Daily)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Initial: Hydroxychloroquine 400mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (200mg twice per day; 400mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
        <group group_id="B2">
          <title>Secondary: Hydroxychloroquine 800mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (400mg twice per day; 800mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
        <group group_id="B3">
          <title>Tertiary: Hydroxychloroquine 400mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (200mg twice per day; 400mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>One patient was unanalyzable</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>One patient was unanalyzable</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>One patient was unanalyzable</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>one patient unanalyzable</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patients With Elevated Par-4 Levels</title>
        <description>Number of patients with 2-fold change in Par-4 levels from baseline to day 14</description>
        <time_frame>Baseline and day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Initial: Hydroxychloroquine 400mg HCQ</title>
            <description>These initial 3 patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.&#xD;
Hydroxychloroquine, 200mg twice dailiy: Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.</description>
          </group>
          <group group_id="O2">
            <title>Secondary: Hydroxychloroquine 800mg HCQ</title>
            <description>Based on data analysis from the initial patients, these patients received 400mg hydroxychloroquine (HCQ) twice daily (800mg/day total) for 14 days prior to surgery.&#xD;
Hydroxychloroquine, 400mg twice daily: Hydroxychloroquine, 400mg twice daily (800mg/day total) was given to subjects for up to 14 days prior to surgery.</description>
          </group>
          <group group_id="O3">
            <title>Tertiary: Hydroxychloroquine 400mg HCQ</title>
            <description>Based on data from the primary and secondary groups, patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.&#xD;
Hydroxychloroquine, 200mg twice dailiy: Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Patients With Elevated Par-4 Levels</title>
          <description>Number of patients with 2-fold change in Par-4 levels from baseline to day 14</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Optimal Biologic Dose of Hydroxychloroquine</title>
        <description>Dose (mg twice daily) wherein 70% of patients exhibit a 2-fold increase in Par-4 levels with a dose-limiting toxicity of no more than 30%.</description>
        <time_frame>Day 14</time_frame>
        <population>All patients</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>Optimal biological dose is calculated from aggregate data of all patients</description>
          </group>
        </group_list>
        <measure>
          <title>Optimal Biologic Dose of Hydroxychloroquine</title>
          <description>Dose (mg twice daily) wherein 70% of patients exhibit a 2-fold increase in Par-4 levels with a dose-limiting toxicity of no more than 30%.</description>
          <population>All patients</population>
          <units>mg twice daily</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14 days</time_frame>
      <desc>Patients were queried about adverse events during study visits.</desc>
      <group_list>
        <group group_id="E1">
          <title>Initial: Hydroxychloroquine 400mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (200mg twice daily; 400mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
        <group group_id="E2">
          <title>Secondary: Hydroxychloroquine 800mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (400mg twice daily; 800mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
        <group group_id="E3">
          <title>Tertiary: Hydroxychloroquine 400mg HCQ</title>
          <description>Hydroxychloroquine 14 days&#xD;
Hydroxychloroquine: Hydroxychloroquine (200mg twice daily, 400mg total) was given to subjects for up to 14 days prior to surgery.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Peng Wang</name_or_title>
      <organization>University of Kentucky</organization>
      <phone>(859) 257-4488</phone>
      <email>p.wang@uky.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02232243
org study id: 14-MULTI-14-MCC
nct id: NCT02232243
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Baseline levels of PAR-4 secreted by normal cells are generally inadequate to cause massive
      apoptosis in cancer cells and drugs that bolster the secretion of PAR-4 would constitute an
      important therapeutic advance.The apoptosis sensitizing features of hydroxychloroquine
      enhance the anti-tumor effects of a broad range of cancer therapeutics. The investigators
      hypothesize that hydroxychloroquine will induce at least 2-fold increase in systemic (plasma)
      PAR-4 levels compared to pre-treatment plasma levels in patients with resectable solid
      tumors.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Patients With Elevated Par-4 Levels
time frame: Baseline and day 14
description: Number of patients with 2-fold change in Par-4 levels from baseline to day 14
measure: Optimal Biologic Dose of Hydroxychloroquine
time frame: Day 14
description: Dose (mg twice daily) wherein 70% of patients exhibit a 2-fold increase in Par-4 levels with a dose-limiting toxicity of no more than 30%.
arm group label: Initial: Hydroxychloroquine 400mg HCQ
arm group type: Experimental
description: These initial 3 patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.
arm group label: Secondary: Hydroxychloroquine 800mg HCQ
arm group type: Experimental
description: Based on data analysis from the initial patients, these patients received 400mg hydroxychloroquine (HCQ) twice daily (800mg/day total) for 14 days prior to surgery.
arm group label: Tertiary: Hydroxychloroquine 400mg HCQ
arm group type: Experimental
description: Based on data from the primary and secondary groups, patients received 200mg hydroxychloroquine (HCQ) twice daily (400mg/day total) for 14 days prior to surgery.
intervention type: Drug
intervention name: Hydroxychloroquine, 200mg twice dailiy
description: Hydroxychloroquine, 200mg twice daily (400mg/day total) was given to subjects for up to 14 days prior to surgery.
arm group label: Initial: Hydroxychloroquine 400mg HCQ
arm group label: Tertiary: Hydroxychloroquine 400mg HCQ
intervention type: Drug
intervention name: Hydroxychloroquine, 400mg twice daily
description: Hydroxychloroquine, 400mg twice daily (800mg/day total) was given to subjects for up to 14 days prior to surgery.
arm group label: Secondary: Hydroxychloroquine 800mg HCQ
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peng Wang, MD, PhD
role: Principal Investigator
affiliation: Lucille P. Markey Cancer Center at University of Kentucky
facility: 
country: United States
citation: Wang P, Burikhanov R, Jayswal R, Weiss HL, Arnold SM, Villano JL, Rangnekar VM. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018 May;9(5-6):190-197. doi: 10.18632/genesandcancer.181.
PMID: 30603055
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Peng Wang, MD PhD
investigator title: Principal Investigator
mesh term: Neoplasms
mesh term: Hydroxychloroquine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 