<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/NCT01723475</url>
  </required_header>
  <id_info>
    <org_study_id>15590</org_study_id>
    <secondary_id>2012-000691-42</secondary_id>
    <nct_id>NCT01723475</nct_id>
  </id_info>
  <brief_title>First-in-man Dose Escalation Study of BAY2010112 in Patients With Prostate Cancer</brief_title>
  <official_title>An Open-label, Phase I, Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY 2010112, Given Once Daily by Subcutaneous Administration or by Continuous Intravenous Infusion, in Subjects With Castration-resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is the first study where BAY2010112 is given to humans. Patients with castration&#xD;
      resistant prostate cancer will be treated. Every patient will receive drug treatment, there&#xD;
      is no placebo group. Patients will receive different dosages of BAY2010112 to determine the&#xD;
      safety, tolerability and maximum tolerated dose (MTD) of BAY2010112.&#xD;
&#xD;
      The study will also assess the pharmacokinetics and the clinical efficacy of BAY2010112.&#xD;
&#xD;
      BAY2010112 will be given daily as subcutaneous injection or as continuous intravenous&#xD;
      infusion. Treatment will be stopped if the tumor continues to grow, if side effects, which&#xD;
      the patient cannot tolerate, occur or if the patient decides to exit treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2012</start_date>
  <completion_date type="Actual">September 26, 2018</completion_date>
  <primary_completion_date type="Actual">July 18, 2018</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 participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 2 years or longer if indicated</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Up to 2 years or longer if indicated</time_frame>
    <description>MTD is measured by adverse event profile at the end of Cycle 1. MTD will be the highest dose level achieved during dose escalation where the incidence of dose-limiting toxicities (DLTs) is below 20%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum drug concentration (Cmax) of BAY2010112 in serum after single and multiple doses administration</measure>
    <time_frame>Cycle 1 Day1 and 15; (1 Cycle is 21 days long)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration versus time curve (AUC) from zero to infinity after single (first) and multiple doses of BAY2010112</measure>
    <time_frame>Cycle 1 (1 Cycle is 21 days long)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>Up to 2 years or longer if indicated</time_frame>
    <description>Tumor response is measured by measurable lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate-specific antigen (PSA) response</measure>
    <time_frame>Up to 2 years or longer if indicated</time_frame>
    <description>PSA response is measured by maximum decline in PSA that occurs at any point after treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>BAY2010112 (s.c.)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BAY2010112 (c.i.v.)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BAY2010112</intervention_name>
    <description>Subcutaneous (s.c.) administration once daily. Starting dose will be 0.5 µg ; dose will be escalated dependent on any dose limiting toxicities</description>
    <arm_group_label>BAY2010112 (s.c.)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BAY2010112</intervention_name>
    <description>Continuous intravenous infusion (c.i.v.) administration. Starting dose will be 5 µg ; dose will be escalated dependent on any dose limiting toxicities.</description>
    <arm_group_label>BAY2010112 (c.i.v.)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male subjects, aged &gt;/= 18 years&#xD;
&#xD;
          -  Subjects with histologically or cytologically proven advanced castration-resistant&#xD;
             prostate cancer (CRPC)&#xD;
&#xD;
               -  who failed at least 1 taxane regimen and are refractory to abiraterone and/or&#xD;
                  enzalutamide therapy OR&#xD;
&#xD;
               -  who have actively refused any treatment which would be regarded standard.&#xD;
&#xD;
          -  Subjects should have undergone bilateral orchiectomy or should be on continuous&#xD;
             androgen deprivation therapy with a gonadotropin releasing hormone agonist or&#xD;
             antagonist.&#xD;
&#xD;
          -  Subjects must have shown progressive disease after discontinuation of anti-androgen&#xD;
             therapy (i.e. flutamide, bicalutamide or nilutamide) before study drug treatment.&#xD;
&#xD;
          -  Total serum testosterone should be less than 50 ng/ml or 1.7 nmol/L&#xD;
&#xD;
          -  Evidence of progressive disease, defined as one or more (Prostate Cancer Working Group&#xD;
             2 (PCWG2) criteria):&#xD;
&#xD;
          -  PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at&#xD;
             least 1 week apart&#xD;
&#xD;
          -  Nodal (in lymph nodes &gt;/= 2cm) or visceral progression as defined by Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST)&#xD;
&#xD;
          -  Appearance of one more new lesions in bone scan&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any anticancer therapy or immunotherapy within 4 weeks of start of first dose&#xD;
&#xD;
          -  Confirmed history or current autoimmune disease or other diseases resulting in&#xD;
             permanent immunosuppression or requiring permanent immunosuppressive therapy&#xD;
&#xD;
          -  Prior radiotherapy (local palliative radiotherapy is permitted)&#xD;
&#xD;
          -  History of allergic reactions to monoclonal antibody therapy&#xD;
&#xD;
          -  History of clinical significant cardiac disease: including unstable angina, acute&#xD;
             myocardial infarction within 6 months prior to first study treatment, congestive heart&#xD;
             failure ≥New York Heart Association (NYHA) Class III), and arrhythmia requiring&#xD;
             therapy except for beta-blockers, calcium channel blockers and digoxin or uncontrolled&#xD;
             hypertension, despite optimal medical management&#xD;
&#xD;
          -  Clinically relevant findings in the electrocardiogram (ECG) such as a second- or&#xD;
             third-degree AV block, prolongation of the QRS complex over 120 msec or of the QT&#xD;
             interval corrected for heart rate (QTc)-interval over 450 msec&#xD;
&#xD;
          -  Current evidence or history of uncured (i.a. any absolute risk of latent infection) of&#xD;
             hepatitis B or C or human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Chronic systemic corticosteroid therapy or any other immunosuppressive therapies&#xD;
             should have been stopped at screening start&#xD;
&#xD;
          -  Seizure disorder requiring therapy (such as steroids or anti-epileptics)&#xD;
&#xD;
          -  Subjects unable to inject the study drug subcutaneously for intended s.c. application&#xD;
&#xD;
          -  Non-suitable for a central venous access for intended c.i.v. administration&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Linz</city>
        <state>Oberösterreich</state>
        <zip>4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wien</city>
        <zip>1100</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Heidelberg</city>
        <state>Baden-Württemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Würzburg</city>
        <state>Bayern</state>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <zip>12200</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.clinicaltrialsregister.eu/</url>
    <description>Click here to find information about studies related to Bayer Healthcare products conducted in Europe</description>
  </link>
  <link>
    <url>https://clinicaltrials.bayer.com/</url>
    <description>Click here to find results for studies related to Bayer products.</description>
  </link>
  <results_reference>
    <citation>Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013 Jun;17(3):385-92. doi: 10.1016/j.cbpa.2013.03.029. Epub 2013 Apr 25.</citation>
    <PMID>23623807</PMID>
  </results_reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>September 25, 2019</last_update_submitted>
  <last_update_submitted_qc>September 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I</keyword>
  <keyword>Dose Escalation</keyword>
  <keyword>Prostate cancer</keyword>
  <keyword>Antibodies</keyword>
  <keyword>Bispecific T-cell Engager (BiTE)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic 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/NCT01723475
org study id: 15590
secondary id: 2012-000691-42
nct id: NCT01723475
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is the first study where BAY2010112 is given to humans. Patients with castration
      resistant prostate cancer will be treated. Every patient will receive drug treatment, there
      is no placebo group. Patients will receive different dosages of BAY2010112 to determine the
      safety, tolerability and maximum tolerated dose (MTD) of BAY2010112.

      The study will also assess the pharmacokinetics and the clinical efficacy of BAY2010112.

      BAY2010112 will be given daily as subcutaneous injection or as continuous intravenous
      infusion. Treatment will be stopped if the tumor continues to grow, if side effects, which
      the patient cannot tolerate, occur or if the patient decides to exit treatment.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Up to 2 years or longer if indicated
measure: Maximum Tolerated Dose (MTD)
time frame: Up to 2 years or longer if indicated
description: MTD is measured by adverse event profile at the end of Cycle 1. MTD will be the highest dose level achieved during dose escalation where the incidence of dose-limiting toxicities (DLTs) is below 20%
measure: Maximum drug concentration (Cmax) of BAY2010112 in serum after single and multiple doses administration
time frame: Cycle 1 Day1 and 15; (1 Cycle is 21 days long)
measure: Area under the concentration versus time curve (AUC) from zero to infinity after single (first) and multiple doses of BAY2010112
time frame: Cycle 1 (1 Cycle is 21 days long)
measure: Tumor response
time frame: Up to 2 years or longer if indicated
description: Tumor response is measured by measurable lesions
measure: Prostate-specific antigen (PSA) response
time frame: Up to 2 years or longer if indicated
description: PSA response is measured by maximum decline in PSA that occurs at any point after treatment
arm group label: BAY2010112 (s.c.)
arm group type: Experimental
arm group label: BAY2010112 (c.i.v.)
arm group type: Experimental
intervention type: Biological
intervention name: BAY2010112
description: Subcutaneous (s.c.) administration once daily. Starting dose will be 0.5 µg ; dose will be escalated dependent on any dose limiting toxicities
arm group label: BAY2010112 (s.c.)
intervention type: Biological
intervention name: BAY2010112
description: Continuous intravenous infusion (c.i.v.) administration. Starting dose will be 5 µg ; dose will be escalated dependent on any dose limiting toxicities.
arm group label: BAY2010112 (c.i.v.)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Germany
url: http://www.clinicaltrialsregister.eu/
description: Click here to find information about studies related to Bayer Healthcare products conducted in Europe
url: https://clinicaltrials.bayer.com/
description: Click here to find results for studies related to Bayer products.
citation: Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013 Jun;17(3):385-92. doi: 10.1016/j.cbpa.2013.03.029. Epub 2013 Apr 25.
PMID: 23623807
responsible party type: Sponsor
mesh term: Prostatic Neoplasms