<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/NCT01672450</url>
  </required_header>
  <id_info>
    <org_study_id>HCI56809</org_study_id>
    <nct_id>NCT01672450</nct_id>
  </id_info>
  <brief_title>A Study of Intratumoral Injection of Interleukin-2 and Ipilimumab in Patients With Unresectable Stages III-IV Melanoma</brief_title>
  <official_title>A Phase I Study of Intratumoral Injection of Interleukin-2 and Ipilimumab in Patients With Unresectable Stages III-IV Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single center, open phase I dose escalation study. This study will assess the&#xD;
      highest tolerable intratumoral dose of ipilimumab (Yervoy) in combination with IL-2&#xD;
      (Proleukin) in patients with unresectable stages III-IV melanoma with accessible cutaneous,&#xD;
      subcutaneous, and/or nodal lesions. The objective is to primarily assess the safety of the&#xD;
      drug combination, and to secondarily obtain preliminary data on the clinical efficacy of the&#xD;
      combination.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>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 Adverse Events per patient</measure>
    <time_frame>24 months</time_frame>
    <description>To assess safety of interleukin-2 and Ipilimumab combination and to select the recommended dose regimen for future phase II studies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Starting and Ending measurements of treated lesions</measure>
    <time_frame>24 months</time_frame>
    <description>Clinical response rate of treated lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Starting and ending measurement of untreated lesions</measure>
    <time_frame>24 months</time_frame>
    <description>Clinical response rate of untreated lesions</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>All patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants in this study will receive the same treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intratumoral Ipilimumab and Interleukin-2</intervention_name>
    <description>Only 1 lesion, 0.5 -2 cm, will be treated. Interleukin-2, 3 mIU IT TIW x 2 weeks (days 1, 3 and 5), then BIW x 6 weeks (days 1 and 4). Escalating doses of Ipilimumab (0.1, 0.25, 0.5, 1, 2, mg) IT weekly x 8 weeks</description>
    <arm_group_label>All patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Histological diagnosis of melanoma, unresectable stages III-IV with accessible cutaneous,&#xD;
        subcutaneous, and/or nodal lesions , according to the AJCC Staging Manual, 7th Edition,&#xD;
        2011.&#xD;
&#xD;
        Note: Patients who are considered to have resectable disease but decline resection are&#xD;
        eligible.&#xD;
&#xD;
          -  At least one lesion &gt; 0.5 cm and &lt; 2 cm&#xD;
&#xD;
          -  ECOG performance status 0, 1 or 2&#xD;
&#xD;
          -  Negative pregnancy test for women of childbearing potential within 7 days of&#xD;
             enrollment on study.&#xD;
&#xD;
          -  WBC &gt; 2,000/mm3; ANC &gt; 1,000/mm3; platelet &gt; 100,000/mm3;hemoglobin &gt; 9 gm/dL (may be&#xD;
             transfused)&#xD;
&#xD;
          -  Serum bilirubin levels &lt;1.5 mg/dL except for patients with Gilbert's syndrome.&#xD;
&#xD;
          -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) &lt; 2.5 X upper&#xD;
             limit of normal, alkaline phosphatase &lt; 2.5 X upper limit of normal.&#xD;
&#xD;
          -  Serum creatinine levels &lt;1.5 mg/dL&#xD;
&#xD;
          -  Women of childbearing potential should be advised to avoid becoming pregnant and men&#xD;
             should be advised to not father a child while receiving treatment with ipilimumab or&#xD;
             interleukin-2. Patients should agree to use an appropriate method of birth control&#xD;
             while on study. Examples of adequate forms of birth control for women include oral or&#xD;
             implanted contraceptives, intrauterine device (IUD), diaphragm with spermicide,&#xD;
             cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual&#xD;
             partner and also based on the judgment of the investigator.&#xD;
&#xD;
          -  Age &gt; 18 years and of any gender or race.&#xD;
&#xD;
          -  Able to provide informed consent and have signed an approved consent form that&#xD;
             conforms to federal and institutional guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent therapy with any other non-protocol anti-cancer therapy&#xD;
&#xD;
          -  Prior local therapy within 2 weeks or prior systemic therapy within 4 weeks of&#xD;
             starting protocol treatment&#xD;
&#xD;
          -  History of any other malignancy requiring active treatment&#xD;
&#xD;
          -  Pre-existing autoimmunity: History of inflammatory bowel disease; history of&#xD;
             symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive&#xD;
             sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g.,&#xD;
             Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.,&#xD;
             Guillain-Barre Syndrome). History of vitiligo is allowed.&#xD;
&#xD;
          -  Chronic use immunosuppressants or systemic corticosteroids. Note: Chronic use is&#xD;
             defined as requiring corticosteroids for greater than one month prior to enrollment on&#xD;
             study. Corticosteroid use for less than 1 month prior to enrollment is allowed, but&#xD;
             use must stop prior to starting study treatment.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease (e.g., uncontrolled hypertension [BP&#xD;
             &gt;150/100], myocardial infarction or stroke within 6 months, unstable angina), New York&#xD;
             Heart Association (NYHA) Grade II or greater congestive heart failure, or serious&#xD;
             cardiac arrhythmia requiring medication&#xD;
&#xD;
          -  Currently active systemic infection&#xD;
&#xD;
          -  Known history of HIV infection or chronic hepatitis B or C.&#xD;
&#xD;
          -  The presence of any other medical or psychiatric disorder that, in the opinion of the&#xD;
             treating physician, would contraindicate the use of the drugs in this protocol or&#xD;
             place the subject at undue risk for treatment complications&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  A history of a severe hypersensitivity reaction to ipilimumab or interleukin-2&#xD;
&#xD;
          -  Any reason why, in the opinion of the investigator, the patient should not participate&#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>Hung Khong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huntsman Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>July 7, 2015</last_update_submitted>
  <last_update_submitted_qc>July 7, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Histologically or cytologically proven melanoma; Stages III-IV; accessible cutaneous, subcutaneous, and/or nodal lesions; ECOG performance status 0 to 2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ipilimumab</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01672450
org study id: HCI56809
nct id: NCT01672450
lead sponsor: 
has dmc: Yes
This is a single center, open phase I dose escalation study. This study will assess the
      highest tolerable intratumoral dose of ipilimumab (Yervoy) in combination with IL-2
      (Proleukin) in patients with unresectable stages III-IV melanoma with accessible cutaneous,
      subcutaneous, and/or nodal lesions. The objective is to primarily assess the safety of the
      drug combination, and to secondarily obtain preliminary data on the clinical efficacy of the
      combination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events per patient
time frame: 24 months
description: To assess safety of interleukin-2 and Ipilimumab combination and to select the recommended dose regimen for future phase II studies
measure: Starting and Ending measurements of treated lesions
time frame: 24 months
description: Clinical response rate of treated lesions
measure: Starting and ending measurement of untreated lesions
time frame: 24 months
description: Clinical response rate of untreated lesions
arm group label: All patients
arm group type: Experimental
description: All participants in this study will receive the same treatment.
intervention type: Drug
intervention name: Intratumoral Ipilimumab and Interleukin-2
description: Only 1 lesion, 0.5 -2 cm, will be treated. Interleukin-2, 3 mIU IT TIW x 2 weeks (days 1, 3 and 5), then BIW x 6 weeks (days 1 and 4). Escalating doses of Ipilimumab (0.1, 0.25, 0.5, 1, 2, mg) IT weekly x 8 weeks
arm group label: All patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hung Khong, MD
role: Principal Investigator
affiliation: Huntsman Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Ipilimumab
mesh term: Interleukin-2