<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/NCT02225366</url>
  </required_header>
  <id_info>
    <org_study_id>2013-0422</org_study_id>
    <secondary_id>5P50CA093459-08</secondary_id>
    <secondary_id>NCI-2014-02012</secondary_id>
    <nct_id>NCT02225366</nct_id>
  </id_info>
  <brief_title>Intratumoral Injections of LL37 for Melanoma</brief_title>
  <official_title>Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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 goal of this clinical research study is to find the appropriate dose of LL37 that can be&#xD;
      given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the&#xD;
      immune system to help control the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Groups:&#xD;
&#xD;
      If you are found to be eligible to take part in this study, you will be assigned to a dose&#xD;
      level of LL37 based on when you join this study. Up to 4 dose levels of LL37 will be tested.&#xD;
      Up to 2 participants will be enrolled at each dose level. The first group of participants&#xD;
      will receive the lowest dose level. Each new group will receive a higher dose than the group&#xD;
      before it, if no intolerable side effects were seen. This will continue until the highest&#xD;
      tolerable dose of LL37 is found.&#xD;
&#xD;
      Study Drug Administration:&#xD;
&#xD;
      One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors. The injections will&#xD;
      be done in the clinic.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      Within 1 week before your first study drug injection:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  You will have a punch biopsy of a tumor. To collect a punch biopsy, the area of skin is&#xD;
           numbed with anesthetic and a small cut is made to remove all or part of the affected&#xD;
           tissue.&#xD;
&#xD;
        -  Blood (about 1 teaspoon) will be drawn for routine tests.&#xD;
&#xD;
        -  The tumors will be measured and photographed. Your private areas will be covered (as&#xD;
           much as possible), and a picture of your face will not be taken unless there are tumors&#xD;
           on your face.&#xD;
&#xD;
      On Day 1:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 1 teaspoon) will be drawn for routine tests.&#xD;
&#xD;
      On Day 2, you will have a punch biopsy of one of the injected tumors.&#xD;
&#xD;
      At Weeks 1, 2, 3, 4, 5, 6, 7, and 8:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 1 teaspoon) will be drawn for routine tests.&#xD;
&#xD;
        -  At Weeks 1, 3, and 5 and 7, blood (about 4 tablespoons) will be drawn to study your&#xD;
           immune response to LL37.&#xD;
&#xD;
      At Week 4, you will have a punch biopsy of one of the injected tumors and one of the tumors&#xD;
      that you did not have an injection in. Photos of the tumors will be taken to show if the&#xD;
      disease has responded to the study drug.&#xD;
&#xD;
      At Week 8:&#xD;
&#xD;
        -  Photos of the LL37 injected sites will be taken to show if the disease has responded to&#xD;
           the study drug.&#xD;
&#xD;
        -  You will have CT scans to check the status of the disease.&#xD;
&#xD;
      Length of Treatment:&#xD;
&#xD;
      You will receive up to 8 weeks of study treatment. You will be taken off study if the disease&#xD;
      gets worse, if intolerable side effects occur, or if you are unable to follow study&#xD;
      directions.&#xD;
&#xD;
      Your participation on the study will be over after the follow-up visits.&#xD;
&#xD;
      Off-Study Visit:&#xD;
&#xD;
      If you have to stop the study treatment earlier than planned because the disease got worse or&#xD;
      you had intolerable side effects:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  The tumors will be photographed and measured.&#xD;
&#xD;
        -  Blood (about 4 teaspoons) will be drawn for routine tests and to study your immune&#xD;
           response to LL37.&#xD;
&#xD;
        -  You will have CT scans to check the status of the disease.&#xD;
&#xD;
        -  You will have a punch biopsy of one of the injected tumors.&#xD;
&#xD;
      These off-study procedures will be completed within 14 days after your last dose of study&#xD;
      treatment. You will be contacted by phone or clinic visit at 30 days (+/- 7 days) after your&#xD;
      last dose to follow up on any drug-related toxicities which were present at the end of study.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      Within 2 weeks after your last study drug dose and every 8-12 weeks after that, you will have&#xD;
      scans to check the status of the disease. Your doctor will decide what type of scans you will&#xD;
      have.&#xD;
&#xD;
      After your last study drug dose, at your routine clinic visits every 3 months for 1 year, the&#xD;
      study staff will ask you about the status of disease, if possible. If you do not plan to&#xD;
      continue to receive medical care at MD Anderson, the study staff will contact you by phone,&#xD;
      email, or letter to ask about the status of disease. The calls should last about 5 minutes.&#xD;
&#xD;
      This is an investigational study. LL37 is not FDA approved or commercially available. It is&#xD;
      currently being used for research purposes only. The study doctor can explain how the study&#xD;
      drug is designed to work.&#xD;
&#xD;
      Up to 36 participants will be treated in this study. All will take part at MD Anderson.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2015</start_date>
  <completion_date type="Actual">November 24, 2020</completion_date>
  <primary_completion_date type="Actual">November 24, 2020</primary_completion_date>
  <phase>Phase 1/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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity</measure>
    <time_frame>once a week, up to 8 weeks duration</time_frame>
    <description>Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting &gt;2 weeks or associated with infection.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37</measure>
    <time_frame>Radiologic evaluations in the form of CT scans of affected disease sites will be performed every 8 weeks (+/- 14 days) while on study, up to 1 year</time_frame>
    <description>Response defined as experiencing either an immune-related complete or partial response (irCR or irPR), and the association between response and disease characteristics and T-cell responses will be assessed using logistic regression.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Intra-Tumoral Injection of LL37</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LL37 administered intratumorally in cutaneous or subcutaneous tumors at least 1 cm in diameter. Patients will receive weekly intratumoral injections of LL37 for up to 8 weeks. The injections will be given every 7 days (+/- 48 hours). Starting dose 250 µg/tumor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LL37</intervention_name>
    <description>Starting dose 250 µg/tumor. The injections will be given every 7 days for up to 8 weeks.</description>
    <arm_group_label>Intra-Tumoral Injection of LL37</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Photographs</intervention_name>
    <description>Tumors measured and photographed one week before receiving LL37, and again at 4 weeks after LL37. Then photographs of the LL37 injected sites taken at 8 weeks.</description>
    <arm_group_label>Intra-Tumoral Injection of LL37</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histologically documented metastatic melanoma with at least 3 cutaneous&#xD;
             lesions measuring over 5mm diameter. At least two lesions must be at least 10mm in&#xD;
             diameter to serve as the injected disease. At least one other lesion measuring at&#xD;
             least 5mm in diameter may serve as the non-injected lesion that will be measurable&#xD;
             disease. Patients will have stage IIIB or IIIC (in-transit lesions with or without&#xD;
             nodal metastases) or stage IV M1A disease with cutaneous or nodal lesions assessable&#xD;
             for administration of LL37. Patients are only eligible if their melanoma deposits are&#xD;
             not amenable to complete surgical excision. Skin lesions that are 5mm or greater are&#xD;
             deemed measurable however lesions that are at least 10mm in diameter will be&#xD;
             preferentially utilized for LL37 injection.&#xD;
&#xD;
          2. Age greater than or equal to 18 years&#xD;
&#xD;
          3. Clinical performance status of ECOG 0-2 within 30 days of signing informed consent.&#xD;
&#xD;
          4. Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's&#xD;
             Syndrome who must have a total bilirubin less than 3.0 mg/dl.&#xD;
&#xD;
          5. Platelet count greater than or equal to 100,000/mm^3&#xD;
&#xD;
          6. WBC &gt;/=3000/mm^3&#xD;
&#xD;
          7. Serum ALT and AST less than three times the upper limit of normal&#xD;
&#xD;
          8. Serum creatinine &lt;/= 2.0 mg/dl&#xD;
&#xD;
          9. Seronegative for HIV antibody&#xD;
&#xD;
         10. Patients with a negative pregnancy test (urine or serum) must be documented within 28&#xD;
             days of starting treatment for women of childbearing potential (WOCBP).&#xD;
&#xD;
         11. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the&#xD;
             patient agrees to continue to use a barrier method of contraception throughout the&#xD;
             study such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence&#xD;
             is an acceptable form of birth control.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active autoimmune disease requiring disease modifying therapy.&#xD;
&#xD;
          2. Concurrent systemic steroid therapy&#xD;
&#xD;
          3. Any form of active primary or secondary immunodeficiency&#xD;
&#xD;
          4. Prior malignancy except the following: adequately treated basal cell or squamous cell&#xD;
             skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer&#xD;
             from which the patient has been disease-free for 2 years.&#xD;
&#xD;
          5. History of immunization with LL37&#xD;
&#xD;
          6. Active systemic infections requiring intravenous antibiotics&#xD;
&#xD;
          7. Prior systemic therapy, radiation therapy, or surgery within 28 days of starting study&#xD;
             treatment&#xD;
&#xD;
          8. Patients who are pregnant or nursing&#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>Rodabe N. Amaria, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <results_first_submitted>November 3, 2021</results_first_submitted>
  <results_first_submitted_qc>December 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 9, 2021</results_first_posted>
  <last_update_submitted>December 7, 2021</last_update_submitted>
  <last_update_submitted_qc>December 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Melanoma</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Antimicrobial peptide</keyword>
  <keyword>LL37</keyword>
  <keyword>Photographs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</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>January 4, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT02225366/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1</title>
          <description>This cohort received starting dose of 250 ug/tumor injection once a week</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2</title>
          <description>This cohort received 500 ug/tumor injection once a week</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1</title>
          <description>This cohort received starting dose of 250 ug/tumor injection once a week</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2</title>
          <description>This cohort received 500 ug/tumor injection once a week</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="3"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" 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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity</title>
        <description>Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting &gt;2 weeks or associated with infection.</description>
        <time_frame>once a week, up to 8 weeks duration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>This cohort received starting dose of 250 ug/tumor injection once a week</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>This cohort received 500 ug/tumor injection once a week</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity</title>
          <description>Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting &gt;2 weeks or associated with infection.</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="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37</title>
        <description>Response defined as experiencing either an immune-related complete or partial response (irCR or irPR), and the association between response and disease characteristics and T-cell responses will be assessed using logistic regression.</description>
        <time_frame>Radiologic evaluations in the form of CT scans of affected disease sites will be performed every 8 weeks (+/- 14 days) while on study, up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>This cohort received starting dose of 250 ug/tumor injection once a week</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>This cohort received 500 ug/tumor injection once a week</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37</title>
          <description>Response defined as experiencing either an immune-related complete or partial response (irCR or irPR), and the association between response and disease characteristics and T-cell responses will be assessed using logistic regression.</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="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>adverse events were collected every week at the time of the injections for up to 8 weeks, All-Cause Mortality was assessed up to 14 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1</title>
          <description>This cohort received starting dose of 250 ug/tumor injection once a week</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2</title>
          <description>This cohort received 500 ug/tumor injection once a week</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.3)</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="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decrease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell decrease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increase</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Squamous Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Actinic Keratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin hypopigmentation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </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>Dr. Rodabe Amaria,MD, Associate Professor, Melanoma Medical Oncology</name_or_title>
      <organization>UT MD Anderson Cancer Center</organization>
      <phone>(713) 792-2921</phone>
      <email>rnamaria@mdanderson.org</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/NCT02225366
org study id: 2013-0422
secondary id: 5P50CA093459-08
secondary id: NCI-2014-02012
nct id: NCT02225366
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The goal of this clinical research study is to find the appropriate dose of LL37 that can be
      given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the
      immune system to help control the disease.
Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a dose
      level of LL37 based on when you join this study. Up to 4 dose levels of LL37 will be tested.
      Up to 2 participants will be enrolled at each dose level. The first group of participants
      will receive the lowest dose level. Each new group will receive a higher dose than the group
      before it, if no intolerable side effects were seen. This will continue until the highest
      tolerable dose of LL37 is found.

      Study Drug Administration:

      One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors. The injections will
      be done in the clinic.

      Study Visits:

      Within 1 week before your first study drug injection:

        -  You will have a physical exam.

        -  You will have a punch biopsy of a tumor. To collect a punch biopsy, the area of skin is
           numbed with anesthetic and a small cut is made to remove all or part of the affected
           tissue.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

        -  The tumors will be measured and photographed. Your private areas will be covered (as
           much as possible), and a picture of your face will not be taken unless there are tumors
           on your face.

      On Day 1:

        -  You will have a physical exam.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

      On Day 2, you will have a punch biopsy of one of the injected tumors.

      At Weeks 1, 2, 3, 4, 5, 6, 7, and 8:

        -  You will have a physical exam.

        -  Blood (about 1 teaspoon) will be drawn for routine tests.

        -  At Weeks 1, 3, and 5 and 7, blood (about 4 tablespoons) will be drawn to study your
           immune response to LL37.

      At Week 4, you will have a punch biopsy of one of the injected tumors and one of the tumors
      that you did not have an injection in. Photos of the tumors will be taken to show if the
      disease has responded to the study drug.

      At Week 8:

        -  Photos of the LL37 injected sites will be taken to show if the disease has responded to
           the study drug.

        -  You will have CT scans to check the status of the disease.

      Length of Treatment:

      You will receive up to 8 weeks of study treatment. You will be taken off study if the disease
      gets worse, if intolerable side effects occur, or if you are unable to follow study
      directions.

      Your participation on the study will be over after the follow-up visits.

      Off-Study Visit:

      If you have to stop the study treatment earlier than planned because the disease got worse or
      you had intolerable side effects:

        -  You will have a physical exam.

        -  The tumors will be photographed and measured.

        -  Blood (about 4 teaspoons) will be drawn for routine tests and to study your immune
           response to LL37.

        -  You will have CT scans to check the status of the disease.

        -  You will have a punch biopsy of one of the injected tumors.

      These off-study procedures will be completed within 14 days after your last dose of study
      treatment. You will be contacted by phone or clinic visit at 30 days (+/- 7 days) after your
      last dose to follow up on any drug-related toxicities which were present at the end of study.

      Follow-Up:

      Within 2 weeks after your last study drug dose and every 8-12 weeks after that, you will have
      scans to check the status of the disease. Your doctor will decide what type of scans you will
      have.

      After your last study drug dose, at your routine clinic visits every 3 months for 1 year, the
      study staff will ask you about the status of disease, if possible. If you do not plan to
      continue to receive medical care at MD Anderson, the study staff will contact you by phone,
      email, or letter to ask about the status of disease. The calls should last about 5 minutes.

      This is an investigational study. LL37 is not FDA approved or commercially available. It is
      currently being used for research purposes only. The study doctor can explain how the study
      drug is designed to work.

      Up to 36 participants will be treated in this study. All will take part at MD Anderson.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity
time frame: once a week, up to 8 weeks duration
description: Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting >2 weeks or associated with infection.
measure: Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37
time frame: Radiologic evaluations in the form of CT scans of affected disease sites will be performed every 8 weeks (+/- 14 days) while on study, up to 1 year
description: Response defined as experiencing either an immune-related complete or partial response (irCR or irPR), and the association between response and disease characteristics and T-cell responses will be assessed using logistic regression.
arm group label: Intra-Tumoral Injection of LL37
arm group type: Experimental
description: LL37 administered intratumorally in cutaneous or subcutaneous tumors at least 1 cm in diameter. Patients will receive weekly intratumoral injections of LL37 for up to 8 weeks. The injections will be given every 7 days (+/- 48 hours). Starting dose 250 µg/tumor.
intervention type: Biological
intervention name: LL37
description: Starting dose 250 µg/tumor. The injections will be given every 7 days for up to 8 weeks.
arm group label: Intra-Tumoral Injection of LL37
intervention type: Other
intervention name: Photographs
description: Tumors measured and photographed one week before receiving LL37, and again at 4 weeks after LL37. Then photographs of the LL37 injected sites taken at 8 weeks.
arm group label: Intra-Tumoral Injection of LL37
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rodabe N. Amaria, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Melanoma
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 