<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/NCT01671774</url>
  </required_header>
  <id_info>
    <org_study_id>GM-IMAB-001-04</org_study_id>
    <secondary_id>2011-005509-64</secondary_id>
    <nct_id>NCT01671774</nct_id>
  </id_info>
  <brief_title>Safety and Activity of IMAB362 in Combination With Zoledronic Acid and Interleukin-2 in CLDN18.2-positive Gastric Cancer</brief_title>
  <acronym>PILOT</acronym>
  <official_title>Multicenter, Open-label, Exploratory Phase I Pilot Study to Investigate Safety, Pharmacodynamics, and Pharmacokinetics of Immunological Effects and Activity of Combining Multiple Doses of IMAB362 With Immunomodulation (Zoledronic Acid, Interleukin-2) in Patients With Advanced Adenocarcinoma of the Stomach, the Lower Esophagus, or the Gastroesophageal Junction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Global Development, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the trial is to assess the immunological effects and their kinetics, the&#xD;
      safety and activity of IMAB362 plus Zoledronic acid with/without low to intermediate doses of&#xD;
      Interleukin-2 in subjects with advanced gastroesophageal cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2012</start_date>
  <completion_date type="Actual">October 13, 2014</completion_date>
  <primary_completion_date type="Actual">October 13, 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability</measure>
    <time_frame>at least 18 months</time_frame>
    <description>Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immune cell profile and kinetics</measure>
    <time_frame>at least 18 months</time_frame>
    <description>Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>at least 18 months</time_frame>
    <description>PFS is defined as the time from registration of therapy to the first observation of disease progression or death from any cause or last tumor evaluation if free of progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective tumor response rate (ORR)</measure>
    <time_frame>at least 18 months</time_frame>
    <description>ORR comprises the fraction of patients with CR, PR according to RECIST v1.1. It is set in relation to the ITT population and PP population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>at least 18 months</time_frame>
    <description>DCR is defined as the fraction of patients with CR or PR or SD according to RECIST v1.1. It is set in relation to the ITT population and PP population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>at least 18 months</time_frame>
    <description>Duration of response is determined as the time when criteria for CR, PR, and SD are first met until the first date that recurrent or progressive disease or death occurs.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>CLDN18.2-positive Gastric Adenocarcinoma</condition>
  <condition>CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction</condition>
  <condition>CLDN18.2-positive Adenocarcinoma of Esophagus</condition>
  <arm_group>
    <arm_group_label>IMAB362 + ZA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IMAB362 + ZA + IL-2 (1 million IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IMAB362 + ZA + IL-2 (3 million IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IMAB362</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMAB362</intervention_name>
    <description>800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle</description>
    <arm_group_label>IMAB362</arm_group_label>
    <arm_group_label>IMAB362 + ZA</arm_group_label>
    <arm_group_label>IMAB362 + ZA + IL-2 (1 million IU)</arm_group_label>
    <arm_group_label>IMAB362 + ZA + IL-2 (3 million IU)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoledronic acid</intervention_name>
    <description>4 mg on d 1 of cycle 1 and cycle 3</description>
    <arm_group_label>IMAB362 + ZA</arm_group_label>
    <arm_group_label>IMAB362 + ZA + IL-2 (1 million IU)</arm_group_label>
    <arm_group_label>IMAB362 + ZA + IL-2 (3 million IU)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin-2 (1 million IU)</intervention_name>
    <description>1 million IU on day 1, 2 and 3 of cycles 1 and 3.</description>
    <arm_group_label>IMAB362 + ZA + IL-2 (1 million IU)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin-2 (3 million IU)</intervention_name>
    <description>3 million IU on day 1, 2 and 3 of cycles 1 and 3.</description>
    <arm_group_label>IMAB362 + ZA + IL-2 (3 million IU)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the stomach, the esophagus or the&#xD;
             gastroesophageal junction&#xD;
&#xD;
          -  Inoperable locally advanced disease, resections with R0, R1 or R2 outcome or&#xD;
             metastatic disease.&#xD;
&#xD;
          -  CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor&#xD;
             tissue sample.&#xD;
&#xD;
          -  Measurable and/or non-measurable disease as defined according to RECIST v1.1&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  ECOG performance status (PS) 0-1&#xD;
&#xD;
          -  Life expectancy &gt; 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior hypersensitivity reaction or intolerance to one of the compounds of the study&#xD;
             treatment&#xD;
&#xD;
          -  Known HIV infection or known symptomatic hepatitis (A, B, C)&#xD;
&#xD;
          -  Clinical symptoms of cerebral metastases&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Patients treated with any bisphosphonate-based therapeutic for any indication during&#xD;
             the previous year&#xD;
&#xD;
          -  Hypocalcemia that requires medication. Corrected (adjusted for serum albumin) serum&#xD;
             calcium &lt; 8 mg/dl (2 mmol/L) or &gt; 12 mg/dL (3.0 mmol/L)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Institut für Klinische Forschung, Krankenhaus Nordwest GmbH</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BAG / Onkologische Schwerpunktpraxis</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leipzig University Hospital, University Cancer Center (UCCL)</name>
      <address>
        <city>Leipzig</city>
        <zip>04109</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ulm University Hospital, Center for Internal Medicine</name>
      <address>
        <city>Ulm</city>
        <zip>89070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piejuras Hospital, Oncology Clinic</name>
      <address>
        <city>Liepaja</city>
        <zip>3401</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riga East University Hospital, LLC, Latvian Oncology Center</name>
      <address>
        <city>Riga</city>
        <zip>LV1038</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Latvia</country>
  </location_countries>
  <removed_countries>
    <country>Bulgaria</country>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>October 16, 2019</last_update_submitted>
  <last_update_submitted_qc>October 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zoledronic Acid</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under &quot;Sponsor Specific Details for Astellas.&quot;</ipd_description>
  </patient_data>
  <!-- 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/NCT01671774
org study id: GM-IMAB-001-04
secondary id: 2011-005509-64
nct id: NCT01671774
lead sponsor: 
has dmc: Yes
The purpose of the trial is to assess the immunological effects and their kinetics, the
      safety and activity of IMAB362 plus Zoledronic acid with/without low to intermediate doses of
      Interleukin-2 in subjects with advanced gastroesophageal cancer.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
measure: Safety and Tolerability
time frame: at least 18 months
description: Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
measure: Immune cell profile and kinetics
time frame: at least 18 months
description: Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.
measure: Progression-free survival (PFS)
time frame: at least 18 months
description: PFS is defined as the time from registration of therapy to the first observation of disease progression or death from any cause or last tumor evaluation if free of progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation.
measure: Objective tumor response rate (ORR)
time frame: at least 18 months
description: ORR comprises the fraction of patients with CR, PR according to RECIST v1.1. It is set in relation to the ITT population and PP population.
measure: Disease control rate (DCR)
time frame: at least 18 months
description: DCR is defined as the fraction of patients with CR or PR or SD according to RECIST v1.1. It is set in relation to the ITT population and PP population.
measure: Duration of response (DOR)
time frame: at least 18 months
description: Duration of response is determined as the time when criteria for CR, PR, and SD are first met until the first date that recurrent or progressive disease or death occurs.
arm group label: IMAB362 + ZA
arm group type: Experimental
description: Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
arm group label: IMAB362 + ZA + IL-2 (1 million IU)
arm group type: Experimental
description: Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
arm group label: IMAB362 + ZA + IL-2 (3 million IU)
arm group type: Experimental
description: Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
arm group label: IMAB362
arm group type: Active Comparator
description: Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.
intervention type: Drug
intervention name: IMAB362
description: 800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
arm group label: IMAB362
arm group label: IMAB362 + ZA
arm group label: IMAB362 + ZA + IL-2 (1 million IU)
arm group label: IMAB362 + ZA + IL-2 (3 million IU)
intervention type: Drug
intervention name: Zoledronic acid
description: 4 mg on d 1 of cycle 1 and cycle 3
arm group label: IMAB362 + ZA
arm group label: IMAB362 + ZA + IL-2 (1 million IU)
arm group label: IMAB362 + ZA + IL-2 (3 million IU)
intervention type: Drug
intervention name: Interleukin-2 (1 million IU)
description: 1 million IU on day 1, 2 and 3 of cycles 1 and 3.
arm group label: IMAB362 + ZA + IL-2 (1 million IU)
intervention type: Drug
intervention name: Interleukin-2 (3 million IU)
description: 3 million IU on day 1, 2 and 3 of cycles 1 and 3.
arm group label: IMAB362 + ZA + IL-2 (3 million IU)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Latvia
country: Bulgaria
country: Czech Republic
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Zoledronic Acid
mesh term: Interleukin-2
sharing ipd: No
ipd description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."