<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/NCT01692262</url>
  </required_header>
  <id_info>
    <org_study_id>D3610C00003</org_study_id>
    <secondary_id>GU86</secondary_id>
    <nct_id>NCT01692262</nct_id>
  </id_info>
  <brief_title>Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.</brief_title>
  <acronym>PYRUS</acronym>
  <official_title>A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity,Safety,Tolerability,and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)(PYRUS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <brief_summary>
    <textblock>
      To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy,&#xD;
      in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated&#xD;
      in patients who have progressed after chemotherapy (Part A) and in patients who have&#xD;
      progressed before receiving chemotherapy (Part B).&#xD;
&#xD;
      Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently&#xD;
      being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational&#xD;
      anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off).&#xD;
&#xD;
      Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having&#xD;
      an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients&#xD;
      on a dose and schedule selected from Part A.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety,&#xD;
      Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate&#xD;
      Cancer (mCRPC) (PYRUS)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)</measure>
    <time_frame>PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)</measure>
    <time_frame>CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate</measure>
    <time_frame>Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status</measure>
    <time_frame>Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Parts A and B: Safety and tolerability of AZD5363 in terms of adverse events, serious adverse events (including death) and safety measures: ECG, ECHO/MUGA, physical examination, pulse, blood pressure, weight and laboratory variables</measure>
    <time_frame>Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts A and B: AZD5363 PK: time to maximum plasma concentration, terminal rate constant,terminal half life, area under plasma concentration time curve, plasma clearance &amp; volume of distribution</measure>
    <time_frame>Multiple AZD5363 PK blood sample assessments.AZD5363 plasma concentration blood samples will be taken on Day 1(pre-dose,2,4,8 hours post-dose);D2(pre-dose);D8(continous) or D11(intermittent) (pre-dose and at 2,4,and 8 hours post-dose);D15,Cyc</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker</measure>
    <time_frame>Multiple PD blood sample assessments.PD blood samples will be taken on the same schedule as PK sample and then Day 1 of every 12 weeks thereafter, and at the discontinuation visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts A and B: Progression-free survival (PFS)</measure>
    <time_frame>Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts A and B: Quality of life (QoL)</measure>
    <time_frame>QOL will be documented from date of randomization and for 12 weeks.</time_frame>
    <description>EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Metastatic Castrate-Resistant Prostate Cancer (mCRPC),</condition>
  <condition>Efficacy,</condition>
  <condition>Safety and Tolerability,</condition>
  <condition>Pharmacokinetics,</condition>
  <condition>Pharmacodynamics,</condition>
  <condition>Tumour Response.</condition>
  <arm_group>
    <arm_group_label>Part A Group 1 Intermittent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recruitment suspended and will not be re-opened. See intervention description below.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A Group 2 Intermittent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recruitment complete. See intervention description below.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This part of the study will not be conducted following a review of data from Part A. See intervention description below.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent dosing of AZD5363</intervention_name>
    <description>Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Recruitment suspended and will not be re-opened.</description>
    <arm_group_label>Part A Group 1 Intermittent</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent dosing of AZD5363</intervention_name>
    <description>Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue to study withdrawal. Recruitment complete.</description>
    <arm_group_label>Part A Group 2 Intermittent</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent dosing of AZD5363</intervention_name>
    <description>Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue until study drug withdrawal. This part of the study will not be conducted.</description>
    <arm_group_label>Part B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of informed consent&#xD;
&#xD;
          -  Males aged 18 years and older&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the prostate without neuroendocrine&#xD;
             differentiation or small cell features for which no standard therapy is currently&#xD;
             considered appropriate&#xD;
&#xD;
          -  Documented evidence of Metastatic Castrate-Resistant Prostate Cancer (mCRPC)&#xD;
&#xD;
          -  Part A: Patients must have received prior docetaxel-based chemotherapy for mCRPC and&#xD;
             have a Circulating Tumour Cell score of 5;&#xD;
&#xD;
          -  Part B: Patients must have progressed before receiving any chemotherapy for mCRPC;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior exposure to agents which inhibit AKT as the primary pharmacological activity&#xD;
&#xD;
          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension, active bleeding diatheses, or active infection including hepatitis B,&#xD;
             hepatitis C, and human immunodeficiency virus&#xD;
&#xD;
          -  Spinal cord compression or brain metastases unless asymptomatic, treated, and stable&#xD;
             and not requiring steroids&#xD;
&#xD;
          -  Clinically significant abnormalities of glucose metabolism&#xD;
&#xD;
          -  Major surgery within the previous 4 weeks&#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>Paul Stockman, MBCHB, PHD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff, Wales</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>June 18, 2014</last_update_submitted>
  <last_update_submitted_qc>June 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Castrate-Resistant Prostate Cancer (mCRPC),</keyword>
  <keyword>adenocarcinoma of the prostate,</keyword>
  <keyword>prostate cancer,</keyword>
  <keyword>progressive disease,</keyword>
  <keyword>advanced disease.</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/NCT01692262
org study id: D3610C00003
secondary id: GU86
nct id: NCT01692262
lead sponsor: 
To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy,
      in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated
      in patients who have progressed after chemotherapy (Part A) and in patients who have
      progressed before receiving chemotherapy (Part B).

      Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently
      being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational
      anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off).

      Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having
      an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients
      on a dose and schedule selected from Part A.
A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety,
      Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate
      Cancer (mCRPC) (PYRUS)
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
time frame: PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks
measure: Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
time frame: CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks
measure: Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
time frame: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent
measure: Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
time frame: Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.
measure: Parts A and B: Safety and tolerability of AZD5363 in terms of adverse events, serious adverse events (including death) and safety measures: ECG, ECHO/MUGA, physical examination, pulse, blood pressure, weight and laboratory variables
time frame: Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.
measure: Parts A and B: AZD5363 PK: time to maximum plasma concentration, terminal rate constant,terminal half life, area under plasma concentration time curve, plasma clearance & volume of distribution
time frame: Multiple AZD5363 PK blood sample assessments.AZD5363 plasma concentration blood samples will be taken on Day 1(pre-dose,2,4,8 hours post-dose);D2(pre-dose);D8(continous) or D11(intermittent) (pre-dose and at 2,4,and 8 hours post-dose);D15,Cyc
measure: Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker
time frame: Multiple PD blood sample assessments.PD blood samples will be taken on the same schedule as PK sample and then Day 1 of every 12 weeks thereafter, and at the discontinuation visit
measure: Parts A and B: Progression-free survival (PFS)
time frame: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.
measure: Parts A and B: Quality of life (QoL)
time frame: QOL will be documented from date of randomization and for 12 weeks.
description: EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires
arm group label: Part A Group 1 Intermittent
arm group type: Experimental
description: Recruitment suspended and will not be re-opened. See intervention description below.
arm group label: Part A Group 2 Intermittent
arm group type: Experimental
description: Recruitment complete. See intervention description below.
arm group label: Part B
arm group type: Experimental
description: This part of the study will not be conducted following a review of data from Part A. See intervention description below.
intervention type: Drug
intervention name: Intermittent dosing of AZD5363
description: Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Recruitment suspended and will not be re-opened.
arm group label: Part A Group 1 Intermittent
intervention type: Drug
intervention name: Intermittent dosing of AZD5363
description: Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue to study withdrawal. Recruitment complete.
arm group label: Part A Group 2 Intermittent
intervention type: Drug
intervention name: Intermittent dosing of AZD5363
description: Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue until study drug withdrawal. This part of the study will not be conducted.
arm group label: Part B
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Stockman, MBCHB, PHD
role: Study Director
affiliation: AstraZeneca
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms