<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/NCT01685268</url>
  </required_header>
  <id_info>
    <org_study_id>AT13387-04</org_study_id>
    <nct_id>NCT01685268</nct_id>
  </id_info>
  <brief_title>A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate</brief_title>
  <official_title>A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate in the Treatment of Castration-Resistant Prostate Cancer (CRPC) no Longer Responding to Abiraterone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astex Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astex Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with&#xD;
      Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with&#xD;
      abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same&#xD;
      doses of abiraterone and steroids they were receiving prior to study entry and will be&#xD;
      randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with&#xD;
      abiraterone. Once the best regimen is established in Part A, based on safety and antitumor&#xD;
      activity, patients will be randomized to the selected treatment regimen and dose of AT13387&#xD;
      in combination with abiraterone or AT13387 alone in Part B (Phase 2).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Safety and tolerability of the combination of AT13387 and abiraterone and to select the most promising treatment regimen in CRPC patients who are no longer responding to treatment with abiraterone alone.</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients with adverse events&#xD;
Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks&#xD;
Change in tumor measurements by RECIST 1.1 every 12 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2]) between single-agent AT13387 and combination of AT13387 plus abiraterone in patients who are no longer responding to treatment with abiraterone alone.</measure>
    <time_frame>12 months</time_frame>
    <description>Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks&#xD;
Change in tumor measurements by RECIST 1.1 every 12 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of combination treatment of AT13387 and abiraterone.</measure>
    <time_frame>24 months</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC) of AT13387 and abiraterone alone and in combination by Week 4&#xD;
Maximum concentration (Cmax) of AT13387 and abiraterone alone and in combination by Week 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics of combination treatment of AT13387 and abiraterone.</measure>
    <time_frame>24 months</time_frame>
    <description>CTC enumeration and characterization every 4 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Assessment of progression free survival as measured by weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>Overall survival as measured in weeks</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Part A, Regimen 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AT13387 given as a 1-hr IV infusion at a starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A, Regimen 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At13387 administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AT13387</intervention_name>
    <description>Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.</description>
    <arm_group_label>Part A, Regimen 1</arm_group_label>
    <arm_group_label>Part A, Regimen 2</arm_group_label>
    <other_name>onalespib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>abiraterone acetate</intervention_name>
    <description>1000 mg PO daily.</description>
    <arm_group_label>Part A, Regimen 1</arm_group_label>
    <arm_group_label>Part A, Regimen 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>5 mg PO twice daily.</description>
    <arm_group_label>Part A, Regimen 1</arm_group_label>
    <arm_group_label>Part A, Regimen 2</arm_group_label>
    <other_name>prednisolone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion:&#xD;
&#xD;
          1. Must have prostate cancer&#xD;
&#xD;
          2. Have received prior castration by orchiectomy and/or hormone therapy&#xD;
&#xD;
          3. Males &gt;18 years of age&#xD;
&#xD;
          4. Normal activity level for self care&#xD;
&#xD;
          5. Have been receiving abiraterone therapy with a steroid for ≥1 month&#xD;
&#xD;
          6. Have disease progression on abiraterone as defined by either PSA progression,&#xD;
             radiographic or bone progression&#xD;
&#xD;
          7. Have adequate bone marrow, liver and kidney function&#xD;
&#xD;
          8. Must be willing to provide pre-existing tumor samples, if this material exists. If&#xD;
             pre-existing samples are not available, a sample must be obtained during screening&#xD;
&#xD;
          9. Must be willing and able to provide written informed consent and comply with the&#xD;
             protocol and study procedures&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or&#xD;
             histone deacetylase (HDAC) inhibitor compound&#xD;
&#xD;
          2. Have received chemotherapy within 4 weeks prior to receiving study drug&#xD;
&#xD;
          3. Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study&#xD;
             drug&#xD;
&#xD;
          4. Hypersensitivity to AT13387 or other components of the drug product&#xD;
&#xD;
          5. Treatment with any investigational drug within 4 weeks prior to the first dose of&#xD;
             study drug&#xD;
&#xD;
          6. Severe systemic diseases or active uncontrolled infections&#xD;
&#xD;
          7. Presence of a life-threatening illness, medical condition, organ system dysfunction,&#xD;
             or other factors&#xD;
&#xD;
          8. Abnormal heart function&#xD;
&#xD;
          9. Other cancer except for adequately treated basal cell or squamous cell carcinoma of&#xD;
             the skin, or superficial bladder cancer, or other cancer from which the subject has&#xD;
             been disease-free for at least 3 years;&#xD;
&#xD;
         10. No known brain or CNS involvement&#xD;
&#xD;
         11. Unable to receive corticosteroids or history of pituitary or adrenal dysfunction&#xD;
&#xD;
         12. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis&#xD;
             C virus or hepatitis B virus&#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>Johann De Bono, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden Foundation Trust Institute of Cancer Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Los Angeles Institute of Urologic Oncology</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists-Fort Myers</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeland Regional Cancer Center</name>
      <address>
        <city>Lakeland</city>
        <state>Florida</state>
        <zip>33805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University School of Medicine</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland, Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Cancer &amp; Blood Disorders</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Alliance, Inc.</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The West Clinic</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialists, PLLC</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de l'Universite de Montreal (CHUM)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2L 4MI</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brighton &amp; Sussex University Hospitals NHS Trust</name>
      <address>
        <city>Brighton</city>
        <zip>BN2 5BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Center</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Surrey</name>
      <address>
        <city>Guildford</city>
        <zip>GU2 7XP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charing Cross Hospital</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Foundation Trust Instute of Cancer Researrch</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie Hospital NHS Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton</name>
      <address>
        <city>Southampton</city>
        <zip>S016 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clatterbridge Cancer Centre NHS Foundation Trust</name>
      <address>
        <city>Wirral</city>
        <zip>CH63 4JY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <disposition_first_submitted>January 8, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>January 8, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">February 5, 2016</disposition_first_posted>
  <last_update_submitted>September 6, 2016</last_update_submitted>
  <last_update_submitted_qc>September 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostate Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Abiraterone Acetate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01685268
org study id: AT13387-04
nct id: NCT01685268
lead sponsor: 
has dmc: No
A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with
      Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with
      abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same
      doses of abiraterone and steroids they were receiving prior to study entry and will be
      randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with
      abiraterone. Once the best regimen is established in Part A, based on safety and antitumor
      activity, patients will be randomized to the selected treatment regimen and dose of AT13387
      in combination with abiraterone or AT13387 alone in Part B (Phase 2).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A: Safety and tolerability of the combination of AT13387 and abiraterone and to select the most promising treatment regimen in CRPC patients who are no longer responding to treatment with abiraterone alone.
time frame: 12 months
description: Number of patients with adverse events
Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks
Change in tumor measurements by RECIST 1.1 every 12 weeks
measure: Part B: Compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2]) between single-agent AT13387 and combination of AT13387 plus abiraterone in patients who are no longer responding to treatment with abiraterone alone.
time frame: 12 months
description: Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks
Change in tumor measurements by RECIST 1.1 every 12 weeks
measure: Pharmacokinetics of combination treatment of AT13387 and abiraterone.
time frame: 24 months
description: Area under the plasma concentration versus time curve (AUC) of AT13387 and abiraterone alone and in combination by Week 4
Maximum concentration (Cmax) of AT13387 and abiraterone alone and in combination by Week 4
measure: Pharmacodynamics of combination treatment of AT13387 and abiraterone.
time frame: 24 months
description: CTC enumeration and characterization every 4 weeks.
measure: Progression free survival
time frame: 24 months
description: Assessment of progression free survival as measured by weeks
measure: Overall survival
time frame: 24 months
description: Overall survival as measured in weeks
arm group label: Part A, Regimen 1
arm group type: Experimental
description: AT13387 given as a 1-hr IV infusion at a starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.
arm group label: Part A, Regimen 2
arm group type: Experimental
description: At13387 administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.
intervention type: Drug
intervention name: AT13387
description: Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.
arm group label: Part A, Regimen 1
arm group label: Part A, Regimen 2
other name: onalespib
intervention type: Drug
intervention name: abiraterone acetate
description: 1000 mg PO daily.
arm group label: Part A, Regimen 1
arm group label: Part A, Regimen 2
intervention type: Drug
intervention name: Prednisone
description: 5 mg PO twice daily.
arm group label: Part A, Regimen 1
arm group label: Part A, Regimen 2
other name: prednisolone
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johann De Bono, MD
role: Principal Investigator
affiliation: Royal Marsden Foundation Trust Institute of Cancer Research
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country: Canada
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Prednisolone
mesh term: Abiraterone Acetate