<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/NCT02211872</url>
  </required_header>
  <id_info>
    <org_study_id>1216.1</org_study_id>
    <nct_id>NCT02211872</nct_id>
  </id_info>
  <brief_title>BI 2536 BS in Patients With Advanced Solid Tumours and Repeated Administration in Patients With Clinical Benefit</brief_title>
  <official_title>An Open Phase I Single Dose Escalation Study of BI 2536 BS Administered Intravenously in Patients With Advanced Solid Tumours With Repeated Administration 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>
      The primary objective of this study was to determine the maximum tolerated dose (MTD) of BI&#xD;
      2536 BS in patients with advanced solid tumours. Secondary objectives were the evaluation of&#xD;
      safety, efficacy, and pharmacokinetics of BI 2536 BS&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2004</start_date>
  <primary_completion_date type="Actual">March 2007</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>Maximum tolerated dose (MTD) for a single dose of BI 2536 BS</measure>
    <time_frame>Up to 16 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD for single doses of BI 2536 BS on 3 consecutive days</measure>
    <time_frame>Up to 16 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of objective treatment response by tumour measurements</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Evaluated according to the response evaluation criteria in solid tumors (RECIST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration of BI 2536 BS analyte in plasma (Cmax)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to maximum concentration of BI 2536 BS in plasma (tmax)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of BI 2536 BS in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of the AUC0-∞ that is obtained by extrapolation (%AUC0-tz)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant in plasma (λz)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of BI 2536 BS in plasma (t1/2)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of BI 2536 BS in the body after intravenous administration (MRT)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total clearance of BI 2536 BS in the plasma after intravascular administration (CL)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution at steady state following intravascular administration (Vss)</measure>
    <time_frame>Pre-dose, up to 216 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of BI 2536 BS that is eliminated in urine from the time point 0 to time point 24/48 (Ae0-24/48)</measure>
    <time_frame>Pre-dose, up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of analyte eliminated in urine from time point 0 to time point 24/48 (fe0-24/48)</measure>
    <time_frame>Pre-dose, up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of BI 2536 BS from the time point 0 to time point 24/48 (CLR,0-24/48)</measure>
    <time_frame>Pre-dose, up to 48 hours afterdrug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Neoplasms</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 2536 BS single rising dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 2536 BS multiple rising doses on three consecutive days (d1-3 schedule)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 2536 BS, intravenous</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with confirmed diagnosis of advanced, non resectable and / or metastatic&#xD;
             solid tumours, who had failed conventional treatment, or for whom no therapy of proven&#xD;
             efficacy exists, or who were not amenable to established forms of treatment&#xD;
&#xD;
          -  Evaluable tumour deposits&#xD;
&#xD;
          -  Age of 18 years or older&#xD;
&#xD;
          -  Life expectancy of at least 6 months&#xD;
&#xD;
          -  Written informed consent consistent with international conference of harmonization&#xD;
             (ICH) - good clinical practice (GCP) and local legislation&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ≤ 2&#xD;
&#xD;
          -  And full recovery from all therapy-related toxicities from previous chemo-, hormone-,&#xD;
             immuno-, or radiotherapies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Serious illness or concomitant non-oncological disease considered by the investigator&#xD;
             to be incompatible with the trial protocol&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Active infectious disease&#xD;
&#xD;
          -  Known brain metastases&#xD;
&#xD;
          -  Second malignancy requiring therapy&#xD;
&#xD;
          -  Absolute neutrophil count less than 1500/mm3&#xD;
&#xD;
          -  Platelet count less than 100 000/mm3&#xD;
&#xD;
          -  Bilirubin greater than 1.5 mg/dL (&gt; 26 μmol/L, international system of units (SI)&#xD;
             equivalent)&#xD;
&#xD;
          -  Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater&#xD;
             than 2.5 times the upper limit of normal (if related to liver metastases greater than&#xD;
             five times the upper limit of normal)&#xD;
&#xD;
          -  Serum creatinine greater than 1.5 mg/dL (&gt; 132 μmol/L, SI unit equivalent)&#xD;
&#xD;
          -  Sexually active women and men who are unwilling to use a medically acceptable method&#xD;
             of contraception&#xD;
&#xD;
          -  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;
          -  Chemo-, radio or immunotherapy within the past four weeks before start of therapy or&#xD;
             concomitantly with this trial&#xD;
&#xD;
          -  Patients unable to comply with the trial protocol&#xD;
&#xD;
          -  Or active alcohol or drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</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>August 2014</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>August 7, 2014</last_update_submitted>
  <last_update_submitted_qc>August 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02211872
org study id: 1216.1
nct id: NCT02211872
lead sponsor: 
The primary objective of this study was to determine the maximum tolerated dose (MTD) of BI
      2536 BS in patients with advanced solid tumours. Secondary objectives were the evaluation of
      safety, efficacy, and pharmacokinetics of BI 2536 BS
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) for a single dose of BI 2536 BS
time frame: Up to 16 weeks
measure: MTD for single doses of BI 2536 BS on 3 consecutive days
time frame: Up to 16 weeks
measure: Assessment of objective treatment response by tumour measurements
time frame: Up to 1 year
description: Evaluated according to the response evaluation criteria in solid tumors (RECIST)
measure: Number of patients with adverse events
time frame: Up to 1 year
measure: Maximum concentration of BI 2536 BS analyte in plasma (Cmax)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Time from dosing to maximum concentration of BI 2536 BS in plasma (tmax)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Area under the concentration-time curve of BI 2536 BS in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Percentage of the AUC0-∞ that is obtained by extrapolation (%AUC0-tz)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Terminal rate constant in plasma (λz)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Terminal half-life of BI 2536 BS in plasma (t1/2)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Mean residence time of BI 2536 BS in the body after intravenous administration (MRT)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Total clearance of BI 2536 BS in the plasma after intravascular administration (CL)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Apparent volume of distribution at steady state following intravascular administration (Vss)
time frame: Pre-dose, up to 216 hours after drug administration
measure: Amount of BI 2536 BS that is eliminated in urine from the time point 0 to time point 24/48 (Ae0-24/48)
time frame: Pre-dose, up to 48 hours after drug administration
measure: Fraction of analyte eliminated in urine from time point 0 to time point 24/48 (fe0-24/48)
time frame: Pre-dose, up to 48 hours after drug administration
measure: Renal clearance of BI 2536 BS from the time point 0 to time point 24/48 (CLR,0-24/48)
time frame: Pre-dose, up to 48 hours afterdrug administration
arm group label: Treatment A
arm group type: Experimental
description: BI 2536 BS single rising dose
arm group label: Treatment B
arm group type: Experimental
description: BI 2536 BS multiple rising doses on three consecutive days (d1-3 schedule)
intervention type: Drug
intervention name: BI 2536 BS, intravenous
arm group label: Treatment A
arm group label: Treatment B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor