<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/NCT03020017</url>
  </required_header>
  <id_info>
    <org_study_id>NU 16C01</org_study_id>
    <secondary_id>STU00203790</secondary_id>
    <secondary_id>NU 16C01</secondary_id>
    <secondary_id>P30CA060553</secondary_id>
    <secondary_id>NCI-2016-02007</secondary_id>
    <nct_id>NCT03020017</nct_id>
  </id_info>
  <brief_title>NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery</brief_title>
  <official_title>A Phase 0 First-In-Human Study Using NU-0129: A Spherical Nucleic Acid (SNA) Gold Nanoparticle Targeting BCL2L12 in Recurrent Glioblastoma Multiforme or Gliosarcoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to evaluate the safety of the study drug, NU-0129,&#xD;
      based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent&#xD;
      glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the&#xD;
      surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine&#xD;
      the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that&#xD;
      carry blood to the brain). Once within the tumor, the nucleic acid component is able to&#xD;
      target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated&#xD;
      with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of&#xD;
      programmed cell death, thus promoting tumor growth. Researchers think that targeting the&#xD;
      Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma&#xD;
      multiforme (GBM) or gliosarcoma (GS).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To analyze drug concentration in serum at specific time points after drug administration.&#xD;
&#xD;
      II. To demonstrate intratumoral penetration of NU-0129. III. To assess the feasibility of&#xD;
      giving NU-0129 as a standard treatment for recurrent GBM or GS.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To analyze tumor tissue for Bcl2L12 expression levels after NU-0129 administration.&#xD;
&#xD;
      II. Preliminary response (progression free survival [PFS] and overall survival [OS] at 6&#xD;
      months; overall response rate [ORR]).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive NU-0129 intravenously (IV) over 20-50 minutes and undergo standard of care&#xD;
      tumor resection within 8-48 hours.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 7, 14, 21, and 28 days and&#xD;
      then every 84 days for up to 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 25, 2017</start_date>
  <completion_date type="Actual">August 19, 2020</completion_date>
  <primary_completion_date type="Actual">September 6, 2018</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With Adverse Events</measure>
    <time_frame>Up to 21 days after study drug administration</time_frame>
    <description>To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:&#xD;
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration</measure>
    <time_frame>At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion</time_frame>
    <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biodistribution of NU-0129 in Tumor Tissue</measure>
    <time_frame>At time of surgery</time_frame>
    <description>Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H&amp;E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility of Giving NU-0129 as a Standard Treatment</measure>
    <time_frame>At time of infusion (8-48 hours prior to resection) and during surgery</time_frame>
    <description>Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NU-0129 Concentration in Blood After Drug Administration Using Half-life</measure>
    <time_frame>At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion</time_frame>
    <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Gliosarcoma</condition>
  <condition>Recurrent Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Treatment (NU-0129)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (NU-0129)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (NU-0129)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Targeted Molecular Therapy</intervention_name>
    <description>Given NU-0129 IV</description>
    <arm_group_label>Treatment (NU-0129)</arm_group_label>
    <other_name>molecularly targeted therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma&#xD;
             (GS)&#xD;
&#xD;
          -  Patients must have measurable disease by Response Assessment in Neuro-Oncology (RANO)&#xD;
             2010 criteria at the time of registration (pre-operative)&#xD;
&#xD;
          -  Patients must have failed at least one regimen of chemo or radiation therapy; NOTE:&#xD;
             There is no limit to the number or types of prior therapy&#xD;
&#xD;
          -  The patient must be a candidate for surgical debulking (either subtotal or gross total&#xD;
             resection); biopsy-only candidates will not be eligible&#xD;
&#xD;
          -  All patients must be capable to voluntarily sign an informed consent indicating that&#xD;
             they are aware of the investigational nature of this study prior to registration&#xD;
&#xD;
          -  Patients must have a Karnofsky performance status of &gt;= 70&#xD;
&#xD;
          -  Patients must have adequate bone marrow, liver, coagulation and renal function within&#xD;
             7days prior to study registration, as defined below:&#xD;
&#xD;
          -  White blood cell count (WBC) &gt;= 3,000/uL&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mm^3&#xD;
&#xD;
          -  Platelet count of &gt;= 100,000/mm^3 (Note: Transfusion or growth factor may be used for&#xD;
             eligibility outside of 7 days)&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 mg/dL (Note: Transfusion may be used for eligibility outside of 7&#xD;
             days)&#xD;
&#xD;
          -  Bilirubin =&lt; 2 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =&lt; 2 x ULN&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Urine protein =&lt; 3 x ULN&#xD;
&#xD;
          -  Cholesterol =&lt; 300 mg/dL&#xD;
&#xD;
          -  International normalized ration (INR) =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Prothrombin time (PT)/partial thromboplastin time (PTT) =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Any patient who has had a recent surgery should have recovered from all effects of the&#xD;
             surgery and be cleared by their surgeon&#xD;
&#xD;
          -  Patients must have confirmed availability of archival or freshly biopsied tumor tissue&#xD;
             meeting protocol-defined specifications (10 unstained slides) prior to study&#xD;
             enrollment&#xD;
&#xD;
          -  Females of child-bearing potential (FOCBP) and males must agree to use adequate&#xD;
             contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to&#xD;
             study entry, for the duration of study participation, and for 28 days following&#xD;
             completion of therapy; should a female patient, or a male patient's partner, become&#xD;
             pregnant or suspect she is pregnant while participating in this study, the patient&#xD;
             should inform her or his treating physician immediately&#xD;
&#xD;
               -  NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a&#xD;
                  tubal ligation, or remaining celibate by choice) who meets the following&#xD;
                  criteria:&#xD;
&#xD;
                    -  Has not undergone a hysterectomy or bilateral oophorectomy&#xD;
&#xD;
                    -  Has had menses at any time in the preceding 12 consecutive months (and&#xD;
                       therefore has not been naturally postmenopausal for &gt; 12 months)&#xD;
&#xD;
          -  FOCBP must have a negative pregnancy test (either urine or serum) within 14 days prior&#xD;
             to registration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have any significant infections or medical illnesses that in the&#xD;
             investigator's opinion cannot be adequately controlled with appropriate therapy or&#xD;
             would compromise the patient's ability to tolerate NU-0129&#xD;
&#xD;
          -  Patients must not have a history of any other cancer unless they are in complete&#xD;
             remission and off of all therapy for that disease for a minimum of 3 years&#xD;
&#xD;
               -  Note: Non-melanoma skin cancer or carcinoma in-situ of the cervix are exceptions&#xD;
                  and may be permitted after discussion with study quality assurance manager (QAM)&#xD;
&#xD;
          -  Patients must not have had radiation therapy within 12 weeks prior to registration&#xD;
&#xD;
          -  Patients must not have had prior cancer therapy (including biologic, cytotoxic, and&#xD;
             experimental therapies, nitrosoureas, and Gliadel wafers or other surgically&#xD;
             implantable antitumor treatment) within 21 days of registration; if questions arise,&#xD;
             please ask the principal investigator (PI)&#xD;
&#xD;
               -  NOTE: Patients must not have Novocure within 24 hours&#xD;
&#xD;
          -  Hormonal tumor therapies should not be administered within 14 days of registration;&#xD;
             exceptions may be discussed with the PI&#xD;
&#xD;
          -  Patients must not have symptomatic hypertension&#xD;
&#xD;
          -  Patients with known human immunodeficiency virus (HIV) infection or chronic or acute&#xD;
             hepatitis B or C are not eligible; Note: Patients do not need to have HIV, hepatitis&#xD;
             B, or hepatitis C testing at screening&#xD;
&#xD;
          -  Female patients who are pregnant or breast feeding are not eligible&#xD;
&#xD;
          -  Patients are not eligible if they are unwilling or unable to comply with the protocol&#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>Priya Kumthekar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>July 11, 2022</results_first_submitted>
  <results_first_submitted_qc>August 5, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 26, 2022</results_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Priya Kumthekar</investigator_full_name>
    <investigator_title>Priya Kumthekar, MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Gliosarcoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <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>April 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03020017/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NU-0129 Treatment</title>
          <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>NU-0129</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Standard of Care Resection</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NU-0129 Treatment</title>
          <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.5" lower_limit="28" upper_limit="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </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="7"/>
                  </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="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="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Adverse Events</title>
        <description>To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:&#xD;
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal</description>
        <time_frame>Up to 21 days after study drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NU-0129 Treatment</title>
            <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Adverse Events</title>
          <description>To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:&#xD;
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal</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="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Experienced any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Experienced an AE related to NU-01289</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Experienced any SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Experienced an SAE related to NU-0129</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration</title>
        <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
        <time_frame>At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NU-0129 Treatment</title>
            <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
          </group>
        </group_list>
        <measure>
          <title>NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration</title>
          <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
          <units>ng/ml</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>siRNA maximum observed plasma concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.1" lower_limit="22.8" upper_limit="123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Au maximum observed plasma concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4290" lower_limit="3120" upper_limit="7140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biodistribution of NU-0129 in Tumor Tissue</title>
        <description>Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H&amp;E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.</description>
        <time_frame>At time of surgery</time_frame>
        <population>2 patients tumor resections resulted in insufficient amount of viable tumor tissue for ICP-MS analysis and were not included in this analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NU-0129 Treatment</title>
            <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
          </group>
        </group_list>
        <measure>
          <title>Biodistribution of NU-0129 in Tumor Tissue</title>
          <description>Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H&amp;E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.</description>
          <population>2 patients tumor resections resulted in insufficient amount of viable tumor tissue for ICP-MS analysis and were not included in this analysis</population>
          <units>percentage of gold &quot;Au&quot;</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.5" spread="8.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Feasibility of Giving NU-0129 as a Standard Treatment</title>
        <description>Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.</description>
        <time_frame>At time of infusion (8-48 hours prior to resection) and during surgery</time_frame>
        <population>Patients who had drug infused and underwent subsequent resection</population>
        <group_list>
          <group group_id="O1">
            <title>NU-0129 Treatment</title>
            <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility of Giving NU-0129 as a Standard Treatment</title>
          <description>Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.</description>
          <population>Patients who had drug infused and underwent subsequent resection</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of patients who had drug infused successfully</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patient who underwent subsequent resection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NU-0129 Concentration in Blood After Drug Administration Using Half-life</title>
        <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
        <time_frame>At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NU-0129 Treatment</title>
            <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
          </group>
        </group_list>
        <measure>
          <title>NU-0129 Concentration in Blood After Drug Administration Using Half-life</title>
          <description>Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.</description>
          <units>hours</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>siRNA half-life</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="0.02" upper_limit="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Au half-life</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="12" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NU-0129 Treatment</title>
          <description>NU-0129 will be administered inpatient at ~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.03)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrospinal fluid leakage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.03)</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="8" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Priya Kumthekar</name_or_title>
      <organization>Northwestern University</organization>
      <phone>312 908 5073</phone>
      <email>p-kumthekar@northwestern.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/NCT03020017
org study id: NU 16C01
secondary id: STU00203790
secondary id: NU 16C01
secondary id: P30CA060553
secondary id: NCI-2016-02007
nct id: NCT03020017
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research study is to evaluate the safety of the study drug, NU-0129,
      based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent
      glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the
      surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine
      the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that
      carry blood to the brain). Once within the tumor, the nucleic acid component is able to
      target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated
      with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of
      programmed cell death, thus promoting tumor growth. Researchers think that targeting the
      Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.
PRIMARY OBJECTIVES:

      I. To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma
      multiforme (GBM) or gliosarcoma (GS).

      SECONDARY OBJECTIVES:

      I. To analyze drug concentration in serum at specific time points after drug administration.

      II. To demonstrate intratumoral penetration of NU-0129. III. To assess the feasibility of
      giving NU-0129 as a standard treatment for recurrent GBM or GS.

      TERTIARY OBJECTIVES:

      I. To analyze tumor tissue for Bcl2L12 expression levels after NU-0129 administration.

      II. Preliminary response (progression free survival [PFS] and overall survival [OS] at 6
      months; overall response rate [ORR]).

      OUTLINE:

      Patients receive NU-0129 intravenously (IV) over 20-50 minutes and undergo standard of care
      tumor resection within 8-48 hours.

      After completion of study treatment, patients are followed up at 7, 14, 21, and 28 days and
      then every 84 days for up to 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients With Adverse Events
time frame: Up to 21 days after study drug administration
description: To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal
measure: NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration
time frame: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
description: Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
measure: Biodistribution of NU-0129 in Tumor Tissue
time frame: At time of surgery
description: Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H&E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.
measure: Feasibility of Giving NU-0129 as a Standard Treatment
time frame: At time of infusion (8-48 hours prior to resection) and during surgery
description: Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.
measure: NU-0129 Concentration in Blood After Drug Administration Using Half-life
time frame: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
description: Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
arm group label: Treatment (NU-0129)
arm group type: Experimental
description: Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (NU-0129)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (NU-0129)
intervention type: Drug
intervention name: Targeted Molecular Therapy
description: Given NU-0129 IV
arm group label: Treatment (NU-0129)
other name: molecularly targeted therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Priya Kumthekar, MD
role: Principal Investigator
affiliation: Northwestern University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Priya Kumthekar
investigator title: Priya Kumthekar, MD
mesh term: Glioblastoma
mesh term: Gliosarcoma
mesh term: Recurrence
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 