<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/NCT02204033</url>
  </required_header>
  <id_info>
    <org_study_id>1170.1</org_study_id>
    <nct_id>NCT02204033</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer</brief_title>
  <official_title>A Phase I Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The general aim of the present study was to assess the safety and tolerability of&#xD;
      intravenously administered Technetium 99m (99mTc) and Rhenium-186 radionuclide (186 Re)&#xD;
      -labelled hMAb BIWA 4, to confirm preferential accumulation in the tumour of 99mTc - labelled&#xD;
      hMAb BIWA 4, to determine the maximum tolerated radiation dose of 186 Re-labelled hMAb BIWA 4&#xD;
      and to propose a safety dose for phase II development.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 1999</start_date>
  <primary_completion_date type="Actual">June 2001</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>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 10 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of human-anti-human-antibody (HAHA)</measure>
    <time_frame>after 144 hours post infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs</measure>
    <time_frame>up to 6 weeks after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)</measure>
    <time_frame>at 48 h after infusion</time_frame>
    <description>uptake expressed as percentage of the injected dose per kg tissue (%ID/kg)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunoscintigraphic imaging evaluation (Parts A + B)</measure>
    <time_frame>up to 21 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (Maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>tmax (Time from dosing to the maximum concentration of the analyte in plasma)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>t½ (Terminal half-life of the analyte in plasma)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Vz (Apparent volume of distribution during the terminal phase)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Vss (Apparent volume of distribution under steady-state conditions)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CL (Total body clearance)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MRT (Mean residence time)</measure>
    <time_frame>up to 336 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative urinary excretion of radioactivity over time</measure>
    <time_frame>up to 96 hours after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 6 weeks after infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurence of dose limiting toxicities (DLT)</measure>
    <time_frame>up to 144 hours post infusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)</measure>
    <time_frame>up to 6 weeks after infusion</time_frame>
    <description>Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Actual organ uptake of 99mTC-labelled hMAb BIWA 4</measure>
    <time_frame>at 21 h after infusion</time_frame>
    <description>expressed as % I.D. (injected dose)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumour response according to response criteria of the World Health Organisation (WHO)</measure>
    <time_frame>up to 144 hours after infusion</time_frame>
    <description>assessed by Computer Tomography (CT) and/or by Magnet resonance imaging (MRI) and/or bone scintigraphy and/or by physical examination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4</measure>
    <time_frame>up to 144 hours after infusion</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Head and Neck Neoplasms</condition>
  <arm_group>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>186 Re - labelled hMAb BIWA 4 - escalating dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTc - labelled hMAb BIWA 4</intervention_name>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - high dose</arm_group_label>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - low dose</arm_group_label>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>186 Re - labelled hMAb BIWA 4</intervention_name>
    <arm_group_label>186 Re - labelled hMAb BIWA 4 - escalating dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>unlabelled hMAb BIWA 4 - low dose</intervention_name>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>unlabelled hMAb BIWA 4 - medium dose</intervention_name>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>unlabelled hMAb BIWA 4 - high dose</intervention_name>
    <arm_group_label>99mTc - labelled hMAb BIWA 4 - high dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histological confirmation of squamous cell carcinoma in the head and&#xD;
             neck&#xD;
&#xD;
          -  Patients destined for surgery by means of neck dissection (Part A) or :&#xD;
&#xD;
          -  Patients with either local and/or regional recurrent disease for which curative&#xD;
             treatment options were not available or distant metastases. The tumor deposits had to&#xD;
             be measurable either clinically or by one or more radiological technique (s) (CT, MRI,&#xD;
             bone scintigraphy). Because RIT was expected to be more effective in smaller size&#xD;
             tumor deposits, patients with lesions measuring &gt; 3 cm in greatest dimension were&#xD;
             preferred (Part B)&#xD;
&#xD;
          -  Patients over 18 years of age&#xD;
&#xD;
          -  Patients younger than 80 years of age&#xD;
&#xD;
          -  Patients who had given 'written informed consent'&#xD;
&#xD;
          -  Patients with a life expectancy of at least 3 months&#xD;
&#xD;
          -  Patients with a good performance status: Karnofsky &gt; 60&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life-threatening infection, allergic diathesis, organ failure (bilirubin &gt; 30µmol/l&#xD;
             and/or creatinine &gt; 150 µmol/l) or evidence of a recent myocardial infarction on ECG&#xD;
             or unstable angina pectoris&#xD;
&#xD;
          -  Pre-menopausal women (last menstruation &lt;= 1 year prior to study start)&#xD;
&#xD;
               -  Not surgically sterile (hysterectomy, tubal ligation) and&#xD;
&#xD;
               -  Not practicing acceptable means of birth control, (nor not planned to be&#xD;
                  continued throughout the study). Acceptable methods of birth control include&#xD;
                  oral, implantable or injectable contraceptives&#xD;
&#xD;
          -  Women with a positive serum pregnancy test at baseline&#xD;
&#xD;
          -  Chemotherapy or radiotherapy within 4 weeks before inclusion in the study&#xD;
&#xD;
          -  White blood cell count &lt; 3000/mm³, granulocyte count &lt; 1500/mm³ or platelet count &lt;&#xD;
             100000/mm³&#xD;
&#xD;
          -  Hematological disorders, congestive heart failure, bronchial asthma, alimentary or&#xD;
             contact allergy, severe atopy or allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>July 29, 2014</last_update_submitted>
  <last_update_submitted_qc>July 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 30, 2014</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>Head and Neck Neoplasms</mesh_term>
  </condition_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/NCT02204033
org study id: 1170.1
nct id: NCT02204033
lead sponsor: 
The general aim of the present study was to assess the safety and tolerability of
      intravenously administered Technetium 99m (99mTc) and Rhenium-186 radionuclide (186 Re)
      -labelled hMAb BIWA 4, to confirm preferential accumulation in the tumour of 99mTc - labelled
      hMAb BIWA 4, to determine the maximum tolerated radiation dose of 186 Re-labelled hMAb BIWA 4
      and to propose a safety dose for phase II development.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events
time frame: up to 10 weeks
measure: Presence of human-anti-human-antibody (HAHA)
time frame: after 144 hours post infusion
measure: Number of patients with clinically significant changes in vital signs
time frame: up to 6 weeks after infusion
measure: Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)
time frame: at 48 h after infusion
description: uptake expressed as percentage of the injected dose per kg tissue (%ID/kg)
measure: Immunoscintigraphic imaging evaluation (Parts A + B)
time frame: up to 21 hours after infusion
measure: AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 336 hours after infusion
measure: Cmax (Maximum measured concentration of the analyte in plasma)
time frame: up to 336 hours after infusion
measure: tmax (Time from dosing to the maximum concentration of the analyte in plasma)
time frame: up to 336 hours after infusion
measure: t½ (Terminal half-life of the analyte in plasma)
time frame: up to 336 hours after infusion
measure: Vz (Apparent volume of distribution during the terminal phase)
time frame: up to 336 hours after infusion
measure: Vss (Apparent volume of distribution under steady-state conditions)
time frame: up to 336 hours after infusion
measure: CL (Total body clearance)
time frame: up to 336 hours after infusion
measure: MRT (Mean residence time)
time frame: up to 336 hours after infusion
measure: Cumulative urinary excretion of radioactivity over time
time frame: up to 96 hours after infusion
measure: Number of patients with abnormal changes in laboratory parameters
time frame: up to 6 weeks after infusion
measure: Occurence of dose limiting toxicities (DLT)
time frame: up to 144 hours post infusion
measure: Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)
time frame: up to 6 weeks after infusion
description: Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high
measure: Actual organ uptake of 99mTC-labelled hMAb BIWA 4
time frame: at 21 h after infusion
description: expressed as % I.D. (injected dose)
measure: Tumour response according to response criteria of the World Health Organisation (WHO)
time frame: up to 144 hours after infusion
description: assessed by Computer Tomography (CT) and/or by Magnet resonance imaging (MRI) and/or bone scintigraphy and/or by physical examination
measure: Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4
time frame: up to 144 hours after infusion
arm group label: 99mTc - labelled hMAb BIWA 4 - low dose
arm group type: Experimental
arm group label: 99mTc - labelled hMAb BIWA 4 - medium dose
arm group type: Experimental
arm group label: 99mTc - labelled hMAb BIWA 4 - high dose
arm group type: Experimental
arm group label: 186 Re - labelled hMAb BIWA 4 - escalating dose
arm group type: Experimental
intervention type: Drug
intervention name: 99mTc - labelled hMAb BIWA 4
arm group label: 99mTc - labelled hMAb BIWA 4 - high dose
arm group label: 99mTc - labelled hMAb BIWA 4 - low dose
arm group label: 99mTc - labelled hMAb BIWA 4 - medium dose
intervention type: Drug
intervention name: 186 Re - labelled hMAb BIWA 4
arm group label: 186 Re - labelled hMAb BIWA 4 - escalating dose
intervention type: Drug
intervention name: unlabelled hMAb BIWA 4 - low dose
arm group label: 99mTc - labelled hMAb BIWA 4 - low dose
intervention type: Drug
intervention name: unlabelled hMAb BIWA 4 - medium dose
arm group label: 99mTc - labelled hMAb BIWA 4 - medium dose
intervention type: Drug
intervention name: unlabelled hMAb BIWA 4 - high dose
arm group label: 99mTc - labelled hMAb BIWA 4 - high dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms