<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/NCT01689870</url>
  </required_header>
  <id_info>
    <org_study_id>LUD2012-005</org_study_id>
    <nct_id>NCT01689870</nct_id>
  </id_info>
  <brief_title>Study of the Combination of Anti-OX40 and Ipilimumab in Patients With Metastatic Melanoma</brief_title>
  <official_title>Phase 1/2 Study of the Combination of a Mouse Monoclonal Antibody to OX40 and Ipilimumab in Patients With Metastatic Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig Institute for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AgonOx</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ludwig Institute for Cancer Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, two-phase study combining a dose escalation Phase 1 with a&#xD;
      proof-of-concept Phase 2 in patients with unresectable or metastatic melanoma, for whom&#xD;
      treatment with ipilimumab is indicated.&#xD;
&#xD;
      The purpose of the Phase 1 is to determine the Anti-OX40 Maximum Tolerated Dose (MTD) and the&#xD;
      secondary objectives are anti-OX40 pharmacokinetics, biological activity and the tumor&#xD;
      response assessed by the Immune-related Response Criteria.&#xD;
&#xD;
      The purpose of Phase 2 is to determine tumor response (by irRC) and the secondary objectives&#xD;
      are anti-OX40 pharmacokinetics, biological activity and Safety/Tolerability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">August 2014</completion_date>
  <primary_completion_date type="Anticipated">June 2014</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>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess safety and tolerability according to the National Cancer Institute CTCAE v4.0 (Phase 1 and 2)</measure>
    <time_frame>Up to 16 weeks</time_frame>
    <description>Laboratory tests, vital sign measurements, physical exams and patient interviews will be performed to detect new abnormalities and deteriorations of any pre-existing conditions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess Tumor Response by the Immune-related Response Criteria (Phase 2)</measure>
    <time_frame>Baseline, Week 12 &amp; week 16</time_frame>
    <description>Tumor Response by irRC is defined as irPR or irCR over a period of at least 4 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine Anti-OX40 serum concentrations</measure>
    <time_frame>Baseline, on days 1, 3 &amp; 5 30 minutes after Anti-OX40 end of infusion, and on days 8 and 15</time_frame>
    <description>The serum concentration of Anti-OX40 (CD134) will be determined from its binding to OX40 as measured by ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the biological activity of anti-OX40 in combination with ipilimumab</measure>
    <time_frame>Baseline, Day1, day 3, day 5 day8, day 15, day 22 day 43, day 64, day 85 &amp; 113</time_frame>
    <description>The biological activity of anti-OX40 in combination with ipilimumab will be assessed by:&#xD;
Determining immunologic changes in the tumor microenvironment by characterization of tumor-infiltrating lymphocytes (TILs), assessment of antigen-specific T cell responses and immunohistochemical (IHC) characterization of tumor and peri-tumoral tissue&#xD;
Characterizing circulating T-cell subsets by flow cytometry&#xD;
Assessing antigen specific immune responses by ELISA&#xD;
Characterizing surface markers on lymphocytes and peripheral blood cells by flow cytometry&#xD;
Measuring serum level of soluble factors (cytokine profiling)&#xD;
mRNA/miRNA profiling to analyse gene transcription and/or miRNA expression</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Metastatic Melanoma</condition>
  <arm_group>
    <arm_group_label>Phase 1 Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.1 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.2 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.4 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered i.v. at the Phase 1 Maximum Tolerated Dose over 60 minutes only in the first week on Days 1, 3 and 5.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-OX40</intervention_name>
    <description>Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5</description>
    <arm_group_label>Phase 1 Cohort 1</arm_group_label>
    <arm_group_label>Phase 1 Cohort 2</arm_group_label>
    <arm_group_label>Phase 1 Cohort 3</arm_group_label>
    <arm_group_label>Phase 2 Cohort 4</arm_group_label>
    <other_name>CD134 mab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1</description>
    <arm_group_label>Phase 1 Cohort 1</arm_group_label>
    <arm_group_label>Phase 1 Cohort 2</arm_group_label>
    <arm_group_label>Phase 1 Cohort 3</arm_group_label>
    <arm_group_label>Phase 2 Cohort 4</arm_group_label>
    <other_name>YERVOY</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with unresectable or metastatic melanoma, for whom treatment with Ipilimumab&#xD;
             is indicated&#xD;
&#xD;
          -  Radiologically measurable disease by immune-related Response Criteria&#xD;
&#xD;
          -  ECOG performance status of 0-1.&#xD;
&#xD;
          -  Anticipated lifespan greater than 12 weeks.&#xD;
&#xD;
          -  At the time of day 1 of the study, patients must be at least 3 weeks since surgery&#xD;
&#xD;
          -  At the time of day 1 of the study, patients with brain metastases must be asymptomatic&#xD;
             and, at least 8 weeks without tumor progression after any whole brain radiotherapy, at&#xD;
             least 4 weeks since craniotomy and resection or stereotactic radiosurgery, at least 3&#xD;
             weeks without new brain metastases as evidenced by MRI/CT&#xD;
&#xD;
          -  The following laboratory parameters must be within the ranges specified: Hemoglobin-≥&#xD;
             9 g/dL, WBC-≥ 3.0 x 109/L, INR-≤ 1.5, Total Bilirubin-≤ 1.9 g/dL &amp; AST/ALT-≤ 3 x ULN&#xD;
&#xD;
          -  Have been informed of other treatment options.&#xD;
&#xD;
          -  At least 18 years. Able and willing to give valid written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contraindications for ipilimumab/Yervoy®.&#xD;
&#xD;
          -  Prior exposure to ipilimumab/Yervoy®&#xD;
&#xD;
          -  Prior exposure to Anti-OX40 or a mouse monoclonal antibody.&#xD;
&#xD;
          -  History of severe allergic reactions to any unknown allergens or anti-OX40 Autoimmune&#xD;
             disease except for autoimmune thyroiditis or vitiligo.&#xD;
&#xD;
          -  Unresolved immune related adverse events following prior biological therapy.&#xD;
&#xD;
          -  Metastatic disease to the central nervous system for which other therapeutic options,&#xD;
             including radiotherapy, may be available.&#xD;
&#xD;
          -  Known immunodeficiency or HIV, Hepatitis B or Hepatitis C positivity.&#xD;
&#xD;
          -  Other serious illnesses (e.g., serious infections requiring antibiotics).&#xD;
&#xD;
          -  Participation in any other clinical trial involving another investigational agent&#xD;
             within 4 weeks prior to day 1 of the study.&#xD;
&#xD;
          -  Mental impairment that may compromise the ability to give informed consent and comply&#xD;
             with the requirements of the study.&#xD;
&#xD;
          -  Lack of availability for immunological and clinical follow-up assessments.&#xD;
&#xD;
          -  Women who are breast feeding or pregnant as evidenced by positive serum pregnancy test&#xD;
             (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 72 hours of first&#xD;
             dosing.&#xD;
&#xD;
          -  Women of childbearing potential not using a medically acceptable means of&#xD;
             contraception for the duration of the study.&#xD;
&#xD;
          -  Any condition that, in the clinical judgment of the treating physician, is likely to&#xD;
             prevent the patient from complying with any aspect of the protocol or that may put the&#xD;
             patient at unacceptable risk.&#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>Jedd Wolchok, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brendan D Curti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Providence Health &amp; Services</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>March 2014</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>March 31, 2014</last_update_submitted>
  <last_update_submitted_qc>March 31, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>OX40</keyword>
  <keyword>Anti-OX40</keyword>
  <keyword>Ipilimumab</keyword>
  <keyword>Melanoma</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>
  </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/NCT01689870
org study id: LUD2012-005
nct id: NCT01689870
lead sponsor: 
collaborator: 
has dmc: No
This is an open label, two-phase study combining a dose escalation Phase 1 with a
      proof-of-concept Phase 2 in patients with unresectable or metastatic melanoma, for whom
      treatment with ipilimumab is indicated.

      The purpose of the Phase 1 is to determine the Anti-OX40 Maximum Tolerated Dose (MTD) and the
      secondary objectives are anti-OX40 pharmacokinetics, biological activity and the tumor
      response assessed by the Immune-related Response Criteria.

      The purpose of Phase 2 is to determine tumor response (by irRC) and the secondary objectives
      are anti-OX40 pharmacokinetics, biological activity and Safety/Tolerability.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assess safety and tolerability according to the National Cancer Institute CTCAE v4.0 (Phase 1 and 2)
time frame: Up to 16 weeks
description: Laboratory tests, vital sign measurements, physical exams and patient interviews will be performed to detect new abnormalities and deteriorations of any pre-existing conditions
measure: Assess Tumor Response by the Immune-related Response Criteria (Phase 2)
time frame: Baseline, Week 12 & week 16
description: Tumor Response by irRC is defined as irPR or irCR over a period of at least 4 weeks
measure: Determine Anti-OX40 serum concentrations
time frame: Baseline, on days 1, 3 & 5 30 minutes after Anti-OX40 end of infusion, and on days 8 and 15
description: The serum concentration of Anti-OX40 (CD134) will be determined from its binding to OX40 as measured by ELISA
measure: Assess the biological activity of anti-OX40 in combination with ipilimumab
time frame: Baseline, Day1, day 3, day 5 day8, day 15, day 22 day 43, day 64, day 85 & 113
description: The biological activity of anti-OX40 in combination with ipilimumab will be assessed by:
Determining immunologic changes in the tumor microenvironment by characterization of tumor-infiltrating lymphocytes (TILs), assessment of antigen-specific T cell responses and immunohistochemical (IHC) characterization of tumor and peri-tumoral tissue
Characterizing circulating T-cell subsets by flow cytometry
Assessing antigen specific immune responses by ELISA
Characterizing surface markers on lymphocytes and peripheral blood cells by flow cytometry
Measuring serum level of soluble factors (cytokine profiling)
mRNA/miRNA profiling to analyse gene transcription and/or miRNA expression
arm group label: Phase 1 Cohort 1
arm group type: Experimental
description: Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.1 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
arm group label: Phase 1 Cohort 2
arm group type: Experimental
description: Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.2 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
arm group label: Phase 1 Cohort 3
arm group type: Experimental
description: Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.4 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
arm group label: Phase 2 Cohort 4
arm group type: Experimental
description: Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered i.v. at the Phase 1 Maximum Tolerated Dose over 60 minutes only in the first week on Days 1, 3 and 5.
intervention type: Drug
intervention name: Anti-OX40
description: Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5
arm group label: Phase 1 Cohort 1
arm group label: Phase 1 Cohort 2
arm group label: Phase 1 Cohort 3
arm group label: Phase 2 Cohort 4
other name: CD134 mab
intervention type: Drug
intervention name: Ipilimumab
description: Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1
arm group label: Phase 1 Cohort 1
arm group label: Phase 1 Cohort 2
arm group label: Phase 1 Cohort 3
arm group label: Phase 2 Cohort 4
other name: YERVOY
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jedd Wolchok, MD, PhD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Brendan D Curti, MD
role: Principal Investigator
affiliation: Providence Health & Services
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Ipilimumab