<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/NCT01705483</url>
  </required_header>
  <id_info>
    <org_study_id>9853-CL-0101</org_study_id>
    <nct_id>NCT01705483</nct_id>
  </id_info>
  <brief_title>A Phase 1, Dose Escalation Study to Assess the Safety and Tolerability of ASP9853 With Either Docetaxel or Paclitaxel in Patients With Advanced Non-hematologic Malignancies</brief_title>
  <official_title>A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP9853 in Combination With Either Docetaxel or Paclitaxel in Subjects With Advanced Non-hematologic Malignancies</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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and tolerability and pharmacokinetics of&#xD;
      ASP9853 combined with docetaxel or with paclitaxel in subjects with advanced non-hematologic&#xD;
      malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a two part study. Part 1 will test increasing dose levels of ASP9853 in combination&#xD;
      with docetaxel. Part 2 will test increasing doses of ASP9853 combined with paclitaxel. Each&#xD;
      part will determine the maximum tolerated dose and recommended Phase 2 dose for ASP9853 in&#xD;
      combination with each taxane. Preliminary evidence of antitumor activity of ASP9853 in&#xD;
      combination with docetaxel or with paclitaxel also will be explored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Based on the results of the Phase 1 data, the company decided not to pursue the development of&#xD;
    this drug at this time.&#xD;
  </why_stopped>
  <start_date type="Actual">August 28, 2012</start_date>
  <completion_date type="Actual">June 11, 2014</completion_date>
  <primary_completion_date type="Actual">June 11, 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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs</measure>
    <time_frame>Duration of study (24 months) to Final Study Visit, up to ≥ 30 days after last dose of ASP9853</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) Profile for ASP9853: AUC24, AUClast, AUCinf, Cmax, Ctrough, tmax, t1/2, CL/F, and Vz/F</measure>
    <time_frame>Parts 1 and 2, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period following ASP9853 dosing; Days 8 and 15: pre-dose, Cycles 2 + , Day 1: predose</time_frame>
    <description>Area under the plasma concentration curve at 24 hours (AUC24), AUC from time zero to time of last measurable concentration (AUClast), AUC with the last concentration extrapolated to infinity (AUCinf), Maximum concentration (Cmax), Trough plasma concentration (Ctrough),Time to attain Cmax (Tmax), Apparent terminal elimination half-life (T1/2), Oral clearance (CL/F), and Volume of distribution during the terminal phase (Vz/F)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) Profile for Docetaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss</measure>
    <time_frame>Part 1, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period</time_frame>
    <description>Clearance (CL), Distribution volume, steady state (Vd ss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) Profile for Paclitaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss</measure>
    <time_frame>Part 2: Cycle 1: Day 1: Pre-dose and 9 times within the 24 hour period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Treatment start to final Study Visit , up to 24 months</time_frame>
    <description>The proportion of subjects with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>CR or PR response until last study visit at which a tumor assessment or an assessment of clinical disease progression is performed, up to 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Pharmacokinetics of ASP9853</condition>
  <condition>Non-hematologic Malignancies</condition>
  <arm_group>
    <arm_group_label>Part 1: ASP9853 with docetaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 docetaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: ASP9853 with paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose for ASP9853 determined as one dose level below maximum tolerated dose (MTD) determined in Part 1, 2 paclitaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ASP9853</intervention_name>
    <description>oral</description>
    <arm_group_label>Part 1: ASP9853 with docetaxel</arm_group_label>
    <arm_group_label>Part 2: ASP9853 with paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>intravenous (IV)</description>
    <arm_group_label>Part 1: ASP9853 with docetaxel</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Taxol</description>
    <arm_group_label>Part 2: ASP9853 with paclitaxel</arm_group_label>
    <other_name>intravenous (IV)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject must have a histologically or cytologically confirmed incurable, locally&#xD;
             advanced, or metastatic non-hematologic malignancy that has progressed or failed to&#xD;
             respond to regimens or therapies known to provide clinical benefit&#xD;
&#xD;
          -  Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          -  Subject must have recovered from the effects of prior systemic antineoplastic or&#xD;
             radiation therapy(s) to ≤ Grade 1 severity or to subject's baseline values, excluding&#xD;
             alopecia&#xD;
&#xD;
          -  Subject agrees not to participate in another interventional study while on treatment&#xD;
&#xD;
        Female subject must be either:&#xD;
&#xD;
        Of non child bearing potential:&#xD;
&#xD;
          -  post-menopausal (defined as at least 1 year without any menses) prior to Screening or&#xD;
&#xD;
          -  documented surgically sterile or status post hysterectomy (at least 1 month prior to&#xD;
             Screening)&#xD;
&#xD;
        Or, if of childbearing potential:&#xD;
&#xD;
          -  must have a negative serum pregnancy test at Screening and&#xD;
&#xD;
          -  must use two forms of birth control (at least one of which must be a barrier method)&#xD;
             starting at Screening and throughout the study period and for 28 days after final&#xD;
             study drug administration&#xD;
&#xD;
        Acceptable forms include:&#xD;
&#xD;
          -  Established use of oral, injected or implanted hormonal methods of contraception.&#xD;
&#xD;
          -  Placement of an intrauterine device (IUD) or intrauterine system (IUS).&#xD;
&#xD;
          -  Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault&#xD;
             caps) with spermicidal&#xD;
&#xD;
          -  foam/gel/film/cream/suppository&#xD;
&#xD;
          -  Female subject must not donate ova starting at Screening and throughout the study&#xD;
             period and for 28 days after final study drug administration.&#xD;
&#xD;
          -  Male subject must not donate sperm starting at Screening and throughout the study&#xD;
             period and for 28 days after final study drug administration.&#xD;
&#xD;
          -  Subject with adequate bone marrow, renal, and hepatic function at baseline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has received more than 3 prior cytotoxic agent-containing regimens&#xD;
&#xD;
          -  Subjects with prior anaphylactic or hypersensitivity reaction to prior taxane therapy&#xD;
&#xD;
          -  Subject with symptomatic central nervous system (CNS) metastases or leptomeningeal&#xD;
             involvement&#xD;
&#xD;
          -  Subjects who received treatments with any of the following:&#xD;
&#xD;
               -  Systemic chemotherapy within 21 days&#xD;
&#xD;
               -  Nitrosoureas or mitomycin C within 42 days&#xD;
&#xD;
               -  Radiotherapy to ≥ 25% of hematopoietically active bone marrow within 21 days&#xD;
&#xD;
          -  Subject had major surgical procedure within 28 days or anticipates need for major&#xD;
             surgical procedure during course of the study&#xD;
&#xD;
          -  Female subjects who are breastfeeding at Screening or during the study period and for&#xD;
             28 days after final study drug administration.&#xD;
&#xD;
          -  Subject with peripheral neuropathy &gt; Grade 1 at baseline&#xD;
&#xD;
          -  Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or&#xD;
             suspected active hepatitis C infection; or known human immunodeficiency virus (HIV)&#xD;
             positive&#xD;
&#xD;
          -  Subject with malabsorption syndrome or disease or condition significantly affecting&#xD;
             gastrointestinal function&#xD;
&#xD;
          -  Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic&#xD;
             disorders, or significant psychological conditions at baseline&#xD;
&#xD;
          -  Subject with clinically significant electrocardiogram (ECG) abnormalities on 12 lead&#xD;
             ECG performed within 14 days before start of study drug&#xD;
&#xD;
          -  Subject who has received strong inhibitors or inducers of CYP3A4 within two weeks&#xD;
             prior to start of study treatment and while on study&#xD;
&#xD;
          -  Subject has participated in any interventional clinical study or has been treated with&#xD;
             any investigational drugs within 30 days or 5 half lives, whichever is longer, prior&#xD;
             to the initiation of Screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Astellas Pharma Global Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Center</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://astellasclinicalstudyresults.com/study.aspx?ID=302</url>
    <description>Link to results on the Astellas Clinical Study Results website</description>
  </link>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>May 29, 2019</last_update_submitted>
  <last_update_submitted_qc>May 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ASP9853</keyword>
  <keyword>Docetaxel</keyword>
  <keyword>Paclitaxel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Docetaxel</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/NCT01705483
org study id: 9853-CL-0101
nct id: NCT01705483
lead sponsor: 
has dmc: No
The purpose of this study is to determine the safety and tolerability and pharmacokinetics of
      ASP9853 combined with docetaxel or with paclitaxel in subjects with advanced non-hematologic
      malignancies.
This is a two part study. Part 1 will test increasing dose levels of ASP9853 in combination
      with docetaxel. Part 2 will test increasing doses of ASP9853 combined with paclitaxel. Each
      part will determine the maximum tolerated dose and recommended Phase 2 dose for ASP9853 in
      combination with each taxane. Preliminary evidence of antitumor activity of ASP9853 in
      combination with docetaxel or with paclitaxel also will be explored.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs
time frame: Duration of study (24 months) to Final Study Visit, up to ≥ 30 days after last dose of ASP9853
measure: Pharmacokinetics (PK) Profile for ASP9853: AUC24, AUClast, AUCinf, Cmax, Ctrough, tmax, t1/2, CL/F, and Vz/F
time frame: Parts 1 and 2, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period following ASP9853 dosing; Days 8 and 15: pre-dose, Cycles 2 + , Day 1: predose
description: Area under the plasma concentration curve at 24 hours (AUC24), AUC from time zero to time of last measurable concentration (AUClast), AUC with the last concentration extrapolated to infinity (AUCinf), Maximum concentration (Cmax), Trough plasma concentration (Ctrough),Time to attain Cmax (Tmax), Apparent terminal elimination half-life (T1/2), Oral clearance (CL/F), and Volume of distribution during the terminal phase (Vz/F)
measure: Pharmacokinetics (PK) Profile for Docetaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss
time frame: Part 1, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period
description: Clearance (CL), Distribution volume, steady state (Vd ss)
measure: Pharmacokinetics (PK) Profile for Paclitaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss
time frame: Part 2: Cycle 1: Day 1: Pre-dose and 9 times within the 24 hour period
measure: Objective response rate (ORR)
time frame: Treatment start to final Study Visit , up to 24 months
description: The proportion of subjects with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.1
measure: Duration of response (DOR)
time frame: CR or PR response until last study visit at which a tumor assessment or an assessment of clinical disease progression is performed, up to 24 months
arm group label: Part 1: ASP9853 with docetaxel
arm group type: Experimental
description: 2 docetaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts
arm group label: Part 2: ASP9853 with paclitaxel
arm group type: Experimental
description: Starting dose for ASP9853 determined as one dose level below maximum tolerated dose (MTD) determined in Part 1, 2 paclitaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts
intervention type: Drug
intervention name: ASP9853
description: oral
arm group label: Part 1: ASP9853 with docetaxel
arm group label: Part 2: ASP9853 with paclitaxel
intervention type: Drug
intervention name: Docetaxel
description: intravenous (IV)
arm group label: Part 1: ASP9853 with docetaxel
other name: Taxotere
intervention type: Drug
intervention name: Paclitaxel
description: Taxol
arm group label: Part 2: ASP9853 with paclitaxel
other name: intravenous (IV)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Astellas Pharma Global Development
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://astellasclinicalstudyresults.com/study.aspx?ID=302
description: Link to results on the Astellas Clinical Study Results website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Paclitaxel
mesh term: Docetaxel
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."