<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/NCT02254031</url>
  </required_header>
  <id_info>
    <org_study_id>1191.3</org_study_id>
    <nct_id>NCT02254031</nct_id>
  </id_info>
  <brief_title>Dose Escalation of Bivatuzumab Mertansine in Female Patients With CD44v6 Positive Recurrent or Metastatic Breast Cancer</brief_title>
  <official_title>An Open Phase I Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Female Patients With CD44v6 Positive Recurrent or Metastatic Breast Cancer With Repeated Administration Courses in Patients With Clinical Benefit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of bivatuzumab mertansine&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>July 2003</start_date>
  <primary_completion_date type="Actual">January 2005</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>Maximum tolerated dose (MTD)</measure>
    <time_frame>up to 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
    <description>graded according to common toxicity criteria (CTC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory examinations</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with development of Human Anti-Human Antibody (HAHA)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration time curve from time zero to time point 168 hours (AUC0-168)</measure>
    <time_frame>up to 168 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration time curve from time point zero to infinity (AUC0-∞)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum serum concentration (Cmax)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum serum concentration (tmax)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (t1/2)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time (MRT)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total body clearance (CL)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state (Vss)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution during the terminal elimination phase (Vz)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough concentration at steady state (Cpre,ss)</measure>
    <time_frame>up to 7 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum serum concentration during the dosing interval τ at steady state (Cmin,ss)</measure>
    <time_frame>up to 7 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity index (LI)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation factor (RA)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
    <description>according to response evaluation criteria in solid tumours (RECIST)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>bivatuzumab mertansine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dose escalation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bivatuzumab mertansine</intervention_name>
    <arm_group_label>bivatuzumab mertansine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. female patients aged 18 years or older&#xD;
&#xD;
          2. patients with breast cancer positive for CD44v6 in at least 50 % of the tumour cells&#xD;
&#xD;
          3. patients with local and / or regional recurrent disease or distant metastases who are&#xD;
             refractory to anthracyclines and / or taxanes (unless contraindications to taxanes and&#xD;
             / or anthracyclines) or not amenable to established treatments&#xD;
&#xD;
          4. measurable tumour deposits by one or more radiological techniques (MRI, CT)&#xD;
&#xD;
          5. life expectancy of at least 6 months&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2&#xD;
&#xD;
          7. patients must have given written informed consent (which must be consistent with&#xD;
             International Conference of Harmonisation-Good Clinical Practice (ICH-GCP) and local&#xD;
             legislation)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. hypersensitivity to humanised or murine antibodies, immunoconjugates or the excipients&#xD;
             of the trial drugs&#xD;
&#xD;
          2. known secondary malignancy requiring therapy&#xD;
&#xD;
          3. active infectious disease&#xD;
&#xD;
          4. brain metastases requiring therapy&#xD;
&#xD;
          5. neuropathy grade 2 or above&#xD;
&#xD;
          6. absolute neutrophil count less than 1,500/mm3&#xD;
&#xD;
          7. platelet count less than 100,000/mm3&#xD;
&#xD;
          8. bilirubin greater than 1.5 mg/dl (&gt; 26 μmol/L, système internationale (SI) unit&#xD;
             equivalent)&#xD;
&#xD;
          9. aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than&#xD;
             3 times the upper limit of normal&#xD;
&#xD;
         10. serum creatinine greater than 1.5 mg/dl (&gt; 132 μmol/L, SI unit equivalent)&#xD;
&#xD;
         11. concomitant non-oncological diseases which are considered relevant for the evaluation&#xD;
             of the safety of the trial drug&#xD;
&#xD;
         12. chemo- or immunotherapy within the past four weeks prior to treatment with the trial&#xD;
             drug or during the trial (except for present trial drug)&#xD;
&#xD;
         13. radiotherapy to breast and thorax region within the past four weeks prior to treatment&#xD;
             with the trial drug or during the trial&#xD;
&#xD;
         14. women who are sexually active and unwilling to use a medically acceptable method of&#xD;
             contraception&#xD;
&#xD;
         15. pregnancy or lactation&#xD;
&#xD;
         16. treatment with other investigational drugs or participation in another clinical trial&#xD;
             within the past four weeks before start of therapy or concomitantly with this trial&#xD;
             (except for present trial drug)&#xD;
&#xD;
         17. patients unable to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 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>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Bivatuzumab mertansine</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/NCT02254031
org study id: 1191.3
nct id: NCT02254031
lead sponsor: 
maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of bivatuzumab mertansine
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: up to 6 months
measure: Incidence of adverse events
time frame: up to 14 days after last drug administration
description: graded according to common toxicity criteria (CTC)
measure: Number of patients with clinically significant findings in laboratory examinations
time frame: up to 14 days after last drug administration
measure: Number of patients with clinically significant findings in vital signs
time frame: up to 14 days after last drug administration
measure: Number of patients with development of Human Anti-Human Antibody (HAHA)
time frame: up to 14 days after last drug administration
measure: Area under the serum concentration time curve from time zero to time point 168 hours (AUC0-168)
time frame: up to 168 hours
measure: Area under the serum concentration time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz)
time frame: up to 14 days after last drug administration
measure: Area under the serum concentration time curve from time point zero to infinity (AUC0-∞)
time frame: up to 14 days after last drug administration
measure: Maximum serum concentration (Cmax)
time frame: up to 14 days after last drug administration
measure: Time to reach maximum serum concentration (tmax)
time frame: up to 14 days after last drug administration
measure: Terminal elimination half-life (t1/2)
time frame: up to 14 days after last drug administration
measure: Mean residence time (MRT)
time frame: up to 14 days after last drug administration
measure: Total body clearance (CL)
time frame: up to 14 days after last drug administration
measure: Volume of distribution at steady state (Vss)
time frame: up to 14 days after last drug administration
measure: Volume of distribution during the terminal elimination phase (Vz)
time frame: up to 14 days after last drug administration
measure: Trough concentration at steady state (Cpre,ss)
time frame: up to 7 days after drug administration
measure: Minimum serum concentration during the dosing interval τ at steady state (Cmin,ss)
time frame: up to 7 days after drug administration
measure: Linearity index (LI)
time frame: up to 14 days after last drug administration
measure: Accumulation factor (RA)
time frame: up to 14 days after last drug administration
measure: Tumor response
time frame: up to 14 days after last drug administration
description: according to response evaluation criteria in solid tumours (RECIST)
arm group label: bivatuzumab mertansine
arm group type: Experimental
description: dose escalation
intervention type: Drug
intervention name: bivatuzumab mertansine
arm group label: bivatuzumab mertansine
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Maytansine
mesh term: Bivatuzumab mertansine