<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/NCT01712685</url>
  </required_header>
  <id_info>
    <org_study_id>130018</org_study_id>
    <secondary_id>13-C-0018</secondary_id>
    <nct_id>NCT01712685</nct_id>
  </id_info>
  <brief_title>Imaging Studies of Kidney Cancer Using 18F-VM4-037</brief_title>
  <official_title>PET Imaging Of Renal Cell Carcinoma With 18F-VM4-037: A Phase II Pilot Study For Detection Of Disease And Correlation With VHL Mutation Status</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - The drug 18F-VM4-037 is being tested for use in cancer imaging studies. It may help tumor&#xD;
      tissue show up more clearly during scans. Researchers want to see how well it works for scans&#xD;
      for people who have kidney cancer.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To test the safety and effectiveness of 18F-VM4-037 during imaging studies of kidney&#xD;
      cancer.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Adults at least 18 years of age with kidney cancer that will be treated with surgery.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           samples will be collected.&#xD;
&#xD;
        -  Participants will have two positron emission tomography (PET) scans of their kidneys.&#xD;
           They will have the scans before and after receiving an injection of 18F-VM4-037. The&#xD;
           scans will take about 2 hours to complete.&#xD;
&#xD;
        -  About 3 weeks after the PET scans, participants will provide tumor tissue samples from&#xD;
           their kidneys.&#xD;
&#xD;
        -  This is a scanning study only. Treatment will not be provided as part of this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
        -  Carbonic Anhydrase IX (CA IX) is a hypoxia-inducible enzyme regulated by the Von Hippel&#xD;
           Lindau (VHL) protein that is commonly overexpressed in certain malignancies including&#xD;
           renal cell carcinoma (RCC) and may have prognostic significance.&#xD;
&#xD;
        -  The VHL gene is commonly mutated or inactivated in RCC tumors and VHL activity regulated&#xD;
           the expression and activity of not only CAIX but also CAXII as well as other genes&#xD;
           critical for tumor angiogenesis such as vascular endothelial growth factor (VEGF),&#xD;
           glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT 3) and platelet derived&#xD;
           growth factor (PDGF).&#xD;
&#xD;
        -  18F-VM4-037 is an imaging drug product formulation which binds to the active site ligand&#xD;
           of CA-IX and also binds to CAXII. We propose to evaluate 18F-VM4-037 as a positron&#xD;
           emission imaging (PET) radiopharmaceutical for the in vivo detection of CA-IX and CAXII&#xD;
           in renal tumors.&#xD;
&#xD;
      STUDY OBJECTIVES&#xD;
&#xD;
      PRIMARY OBJECTIVE:&#xD;
&#xD;
        -  To evaluate the biodistribution of 18F-VM4-037 within tumor and non-tumor tissues.&#xD;
&#xD;
        -  To assess safety of 18F-VM4-037 in patients with primary or metastatic RCC.&#xD;
&#xD;
      ELIGIBILITY:&#xD;
&#xD;
        -  Subject is greater than or equal to 18 years old, Eastern Cooperative Oncology Group&#xD;
           (ECOG) 0-2.&#xD;
&#xD;
        -  Subject must have confirmed primary RCC (greater than or equal to 2.5cm) in diameter on&#xD;
           conventional imaging modality or extrarenal/extrahepatic RCC lesion (greater than or&#xD;
           equal to 1cm).&#xD;
&#xD;
      DESIGN:&#xD;
&#xD;
      - Twenty subjects with primary RCC greater than or equal to 2.5cm in diameter or&#xD;
      extrarenal/extrahepatic lesion suspicious for metastatic RCC (greater than or equal to 1cm in&#xD;
      diameter) scheduled for clinically indicated surgery or biopsy will undergo dynamic&#xD;
      18F-VM4-037 PET/CT imaging. Results will be compared with pathology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was closed to accrual because imaging agent was no longer available.&#xD;
  </why_stopped>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>Phase 2</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>Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)</measure>
    <time_frame>58 days</time_frame>
    <description>The primary outcome measure will be assessed from quantitative measurements (e.g., correlate immunohistochemistry (IHC) results with standardized uptake values (SUVs) from positron emission tomography (PET) images) of the level of uptake of tumor and non tumor tissues into each target lesion, calculated as standardized uptake values. Normal renal parenchyma and muscle are both &quot;non-tumor&quot; tissue.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>58 days</time_frame>
    <description>Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Standard Uptake Value (SUV) for All Target Lesions</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>Mean SUV for primary clear cell renal carcinoma was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Standard Uptake Value (SUV) for Normal Kidney</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene</measure>
    <time_frame>21 days prior to enrollment until closure of the study, approximately 14 months.</time_frame>
    <description>Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distribution Volume Ratio (DVR) for the Primary Kidney Lesions</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>DVR of the lesions was measured by the Logan graphical analysis method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Peak Activity Derived From Time Activity Curve (TAC)</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic (Ki) Rate Constant</measure>
    <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
    <description>Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Carcinoma, Renal Cell</condition>
  <condition>Kidney Neoplasms</condition>
  <arm_group>
    <arm_group_label>Renal Cell Carcinoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F-VM4-037</intervention_name>
    <description>Drug being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans.</description>
    <arm_group_label>Renal Cell Carcinoma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>PET/CT</intervention_name>
    <arm_group_label>Renal Cell Carcinoma</arm_group_label>
    <other_name>Positron emission tomography</other_name>
    <other_name>Computed tomography</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Subject is greater than or equal to18 years old.&#xD;
&#xD;
          -  Subject must be scheduled to undergo surgery or biopsy for primary renal cell&#xD;
             carcinoma (RCC) greater than or equal to 2.5cm in diameter or extrarenal/extrahepatic&#xD;
             metastatic RCC lesion (greater than or equal to1cm in diameter) at the National&#xD;
             Institutes of Health (NIH) Clinical Center based on imaging within 3 weeks.&#xD;
&#xD;
          -  Chemistry parameters: aspartate aminotransferase (AST) and alanine aminotransferase&#xD;
             (ALT) less than or equal to 2 times of the upper limits of normal; total bilirubin, of&#xD;
             &lt; 2 times the upper limits of normal or &lt; 3.0 mg/dl in patients with Gilberts&#xD;
             syndrome.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.&#xD;
&#xD;
          -  Ability to provide informed consent. All subjects must sign an informed consent form&#xD;
             indicating their understanding of the investigational nature and risks of the study&#xD;
             before any protocol-related studies are performed.&#xD;
&#xD;
          -  The subject has a clinically acceptable medical history, physical examination and&#xD;
             vital signs findings during the screening period (from within 21 days before&#xD;
             administration of 18F-VM4-037). Components of an acceptable medical history include no&#xD;
             active infection at the time of enrollment or within 7 days of enrollment, no prior&#xD;
             therapy that results in immunocompromise or impaired renal function (serum creatinine&#xD;
             within 2 weeks prior to positron emission tomography (PET) imaging less than or equal&#xD;
             to1.8 mg/dl and epidermal growth factor receptor (eGFR) must be &gt; 30 ml/min/1.73m^2)&#xD;
             or findings indicating an inability to tolerate the requirements for the scan.&#xD;
             Previous exposure to immunocompromising therapy does not exclude the patient; patients&#xD;
             must have an absolute neutrophil count &gt; 1.5/microL within 2 weeks of PET imaging.&#xD;
&#xD;
          -  If female, must have a negative serum human chorionic gonadotropin (HCG) within 24&#xD;
             hours prior to 18F-VM4-037 injection OR be post menopausal for &gt; 2 years OR be&#xD;
             surgically sterile.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Subjects for whom participating would significantly delay the scheduled standard of&#xD;
             care therapy.&#xD;
&#xD;
          -  Subjects with any coexisting medical or psychiatric condition that is likely to&#xD;
             interfere with study procedures and/or results.&#xD;
&#xD;
          -  Subjects with severe claustrophobia unresponsive to oral anxiolytics.&#xD;
&#xD;
          -  Other medical conditions deemed by the principle investigator (or associates) or&#xD;
             sponsor to make the subject ineligible for protocol procedures.&#xD;
&#xD;
          -  Female subject is pregnant or nursing&#xD;
&#xD;
          -  The site of the target lesion must not have been part of a radiation portal within 6&#xD;
             months of enrollment.&#xD;
&#xD;
          -  Subjects having received another investigational agent within 1 month before&#xD;
             administration of 18F-VM4-037.&#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>Adam R Metwalli, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0018.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ; American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29. doi: 10.3322/canjclin.54.1.8.</citation>
    <PMID>14974761</PMID>
  </reference>
  <reference>
    <citation>Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.</citation>
    <PMID>8493574</PMID>
  </reference>
  <reference>
    <citation>Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JW, Collins D, Majoor-Krakauer D, et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Mar 17;332(6161):268-9. doi: 10.1038/332268a0.</citation>
    <PMID>2894613</PMID>
  </reference>
  <results_reference>
    <citation>Turkbey B, Lindenberg ML, Adler S, Kurdziel KA, McKinney YL, Weaver J, Vocke CD, Anver M, Bratslavsky G, Eclarinal P, Kwarteng G, Lin FI, Yaqub-Ogun N, Merino MJ, Linehan WM, Choyke PL, Metwalli AR. PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study. Abdom Radiol (NY). 2016 Jan;41(1):109-18. doi: 10.1007/s00261-015-0599-1.</citation>
    <PMID>26830617</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>October 20, 2012</study_first_submitted>
  <study_first_submitted_qc>October 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <results_first_submitted>July 31, 2014</results_first_submitted>
  <results_first_submitted_qc>September 16, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 19, 2014</results_first_posted>
  <last_update_submitted>January 10, 2017</last_update_submitted>
  <last_update_submitted_qc>January 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Institutes of Health Clinical Center (CC)</investigator_affiliation>
    <investigator_full_name>Adam Metwalli, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Kidney Neoplasm</keyword>
  <keyword>RCC</keyword>
  <keyword>Biodistribution of 18F-VM4-037</keyword>
  <keyword>CAIX Staining</keyword>
  <keyword>Tumor Angiogenesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Kidney Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Renal Cell Carcinoma</title>
          <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>pt declined to participate before trmt</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Renal Cell Carcinoma</title>
          <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.62" spread="14.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Known Hereditary Renal Cell Carcinoma Mutation</title>
          <description>Demographics information of all the accrued 12 patients; one patient did not receive 18F-VM4-037 injection and positron emission tomography (PET) computed tomography (CT) imaging.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Yes (Von Hippel-Lindau)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Stage</title>
          <description>The T category describes the original tumor. T0: No evidence of primary tumor; T1-T4: Size and/or extent of the primary tumor, with higher numbers indicating larger size/extent. The N category describes whether or not the cancer has reached nearby lymph nodes. N0: No regional lymph node involvement (no cancer found in the lymph nodes). The M category tells whether there are distant metastases (spread of cancer to other parts of the body). M0: No distant metastasis (cancer has not spread to other parts of the body); M1: Distant metastasis (cancer has spread to distant parts of the body).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>TONOMO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T1aNOMO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T3aNOM1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T2NOMO1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T1bNOMO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Histology</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Renalcyst</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clear Renal Cell Carcinoma (ccRCC)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ccRCC with sarcomatoid differentiation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ccRCC with sarcomatoid features</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Grade</title>
          <description>The grades range from 0-4 with higher grades indicating greater size and extent of the tumor.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Not Applicable (N/A)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumor Size (cm)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>2.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2.7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3.3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3.4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3.5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3.6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3.7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5.8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6.89</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>9.3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)</title>
        <description>The primary outcome measure will be assessed from quantitative measurements (e.g., correlate immunohistochemistry (IHC) results with standardized uptake values (SUVs) from positron emission tomography (PET) images) of the level of uptake of tumor and non tumor tissues into each target lesion, calculated as standardized uptake values. Normal renal parenchyma and muscle are both &quot;non-tumor&quot; tissue.</description>
        <time_frame>58 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)</title>
          <description>The primary outcome measure will be assessed from quantitative measurements (e.g., correlate immunohistochemistry (IHC) results with standardized uptake values (SUVs) from positron emission tomography (PET) images) of the level of uptake of tumor and non tumor tissues into each target lesion, calculated as standardized uptake values. Normal renal parenchyma and muscle are both &quot;non-tumor&quot; tissue.</description>
          <units>Standardized uptake value</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tumor tissue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nontumor tissue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Muscle tissue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal kidney tissue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35" spread="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.</description>
        <time_frame>58 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Standard Uptake Value (SUV) for All Target Lesions</title>
        <description>Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Standard Uptake Value (SUV) for All Target Lesions</title>
          <description>Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
          <units>Standard uptake value (SUV)</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.04" lower_limit="0.58" upper_limit="9.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)</title>
        <description>Mean SUV for primary clear cell renal carcinoma was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <population>Mean SUV for ccRCC after excluding Bosnial 3 Cyst (e.g. Bosnial 3 complex cyst) in one participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)</title>
          <description>Mean SUV for primary clear cell renal carcinoma was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
          <population>Mean SUV for ccRCC after excluding Bosnial 3 Cyst (e.g. Bosnial 3 complex cyst) in one participant.</population>
          <units>Standard uptake value (SUV</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.55" lower_limit="0.58" upper_limit="4.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Standard Uptake Value (SUV) for Normal Kidney</title>
        <description>Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Standard Uptake Value (SUV) for Normal Kidney</title>
          <description>Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).</description>
          <units>Standard uptake value (SUV</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.4" lower_limit="19.6" upper_limit="50.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene</title>
        <description>Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.</description>
        <time_frame>21 days prior to enrollment until closure of the study, approximately 14 months.</time_frame>
        <population>5/11 participants had germline VHL testing with 4 having identifiable mutations of the VHL gene. 6/11 participants did not have germline VHL mutation testing due to low index of clinical suspicion although 2/6 had germline analysis for other gene mutations linked to familial renal cell carcinoma conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene</title>
          <description>Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.</description>
          <population>5/11 participants had germline VHL testing with 4 having identifiable mutations of the VHL gene. 6/11 participants did not have germline VHL mutation testing due to low index of clinical suspicion although 2/6 had germline analysis for other gene mutations linked to familial renal cell carcinoma conditions.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Distribution Volume Ratio (DVR) for the Primary Kidney Lesions</title>
        <description>DVR of the lesions was measured by the Logan graphical analysis method.</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Distribution Volume Ratio (DVR) for the Primary Kidney Lesions</title>
          <description>DVR of the lesions was measured by the Logan graphical analysis method.</description>
          <units>Distribution volume ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Peak Activity Derived From Time Activity Curve (TAC)</title>
        <description>The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Peak Activity Derived From Time Activity Curve (TAC)</title>
          <description>The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.</description>
          <units>Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.08" spread="3.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kinetic (Ki) Rate Constant</title>
        <description>Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.</description>
        <time_frame>Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Renal Cell Carcinoma</title>
            <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
          </group>
        </group_list>
        <measure>
          <title>Kinetic (Ki) Rate Constant</title>
          <description>Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.</description>
          <units>1/Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Primary kidney lesions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread=".05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal kidney</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".45" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Liver</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Renal Cell Carcinoma</title>
          <description>This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </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>
    <limitations_and_caveats>Study was closed to accrual because imaging agent was no longer available.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Adam Metwalli</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>301-435-6237</phone>
      <email>metwallia@mail.nih.gov</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/NCT01712685
org study id: 130018
secondary id: 13-C-0018
nct id: NCT01712685
lead sponsor: 
has dmc: No
Background:

      - The drug 18F-VM4-037 is being tested for use in cancer imaging studies. It may help tumor
      tissue show up more clearly during scans. Researchers want to see how well it works for scans
      for people who have kidney cancer.

      Objectives:

      - To test the safety and effectiveness of 18F-VM4-037 during imaging studies of kidney
      cancer.

      Eligibility:

      - Adults at least 18 years of age with kidney cancer that will be treated with surgery.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  Participants will have two positron emission tomography (PET) scans of their kidneys.
           They will have the scans before and after receiving an injection of 18F-VM4-037. The
           scans will take about 2 hours to complete.

        -  About 3 weeks after the PET scans, participants will provide tumor tissue samples from
           their kidneys.

        -  This is a scanning study only. Treatment will not be provided as part of this study.
BACKGROUND:

        -  Carbonic Anhydrase IX (CA IX) is a hypoxia-inducible enzyme regulated by the Von Hippel
           Lindau (VHL) protein that is commonly overexpressed in certain malignancies including
           renal cell carcinoma (RCC) and may have prognostic significance.

        -  The VHL gene is commonly mutated or inactivated in RCC tumors and VHL activity regulated
           the expression and activity of not only CAIX but also CAXII as well as other genes
           critical for tumor angiogenesis such as vascular endothelial growth factor (VEGF),
           glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT 3) and platelet derived
           growth factor (PDGF).

        -  18F-VM4-037 is an imaging drug product formulation which binds to the active site ligand
           of CA-IX and also binds to CAXII. We propose to evaluate 18F-VM4-037 as a positron
           emission imaging (PET) radiopharmaceutical for the in vivo detection of CA-IX and CAXII
           in renal tumors.

      STUDY OBJECTIVES

      PRIMARY OBJECTIVE:

        -  To evaluate the biodistribution of 18F-VM4-037 within tumor and non-tumor tissues.

        -  To assess safety of 18F-VM4-037 in patients with primary or metastatic RCC.

      ELIGIBILITY:

        -  Subject is greater than or equal to 18 years old, Eastern Cooperative Oncology Group
           (ECOG) 0-2.

        -  Subject must have confirmed primary RCC (greater than or equal to 2.5cm) in diameter on
           conventional imaging modality or extrarenal/extrahepatic RCC lesion (greater than or
           equal to 1cm).

      DESIGN:

      - Twenty subjects with primary RCC greater than or equal to 2.5cm in diameter or
      extrarenal/extrahepatic lesion suspicious for metastatic RCC (greater than or equal to 1cm in
      diameter) scheduled for clinically indicated surgery or biopsy will undergo dynamic
      18F-VM4-037 PET/CT imaging. Results will be compared with pathology.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)
time frame: 58 days
description: The primary outcome measure will be assessed from quantitative measurements (e.g., correlate immunohistochemistry (IHC) results with standardized uptake values (SUVs) from positron emission tomography (PET) images) of the level of uptake of tumor and non tumor tissues into each target lesion, calculated as standardized uptake values. Normal renal parenchyma and muscle are both "non-tumor" tissue.
measure: Number of Participants With Adverse Events
time frame: 58 days
description: Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
measure: Mean Standard Uptake Value (SUV) for All Target Lesions
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
measure: Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: Mean SUV for primary clear cell renal carcinoma was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
measure: Mean Standard Uptake Value (SUV) for Normal Kidney
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
measure: Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene
time frame: 21 days prior to enrollment until closure of the study, approximately 14 months.
description: Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.
measure: Distribution Volume Ratio (DVR) for the Primary Kidney Lesions
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: DVR of the lesions was measured by the Logan graphical analysis method.
measure: Time to Peak Activity Derived From Time Activity Curve (TAC)
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.
measure: Kinetic (Ki) Rate Constant
time frame: Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.
description: Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.
arm group label: Renal Cell Carcinoma
arm group type: Experimental
intervention type: Drug
intervention name: 18F-VM4-037
description: Drug being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans.
arm group label: Renal Cell Carcinoma
intervention type: Procedure
intervention name: PET/CT
arm group label: Renal Cell Carcinoma
other name: Positron emission tomography
other name: Computed tomography
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adam R Metwalli, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0018.html
description: NIH Clinical Center Detailed Web Page
citation: Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ; American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29. doi: 10.3322/canjclin.54.1.8.
PMID: 14974761
citation: Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.
PMID: 8493574
citation: Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JW, Collins D, Majoor-Krakauer D, et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Mar 17;332(6161):268-9. doi: 10.1038/332268a0.
PMID: 2894613
citation: Turkbey B, Lindenberg ML, Adler S, Kurdziel KA, McKinney YL, Weaver J, Vocke CD, Anver M, Bratslavsky G, Eclarinal P, Kwarteng G, Lin FI, Yaqub-Ogun N, Merino MJ, Linehan WM, Choyke PL, Metwalli AR. PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study. Abdom Radiol (NY). 2016 Jan;41(1):109-18. doi: 10.1007/s00261-015-0599-1.
PMID: 26830617
responsible party type: Principal Investigator
investigator affiliation: National Institutes of Health Clinical Center (CC)
investigator full name: Adam Metwalli, M.D.
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Kidney Neoplasms
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was closed to accrual because imaging agent was no longer available.
point of contact: 