<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/NCT04425200</url>
  </required_header>
  <id_info>
    <org_study_id>D081LR00002</org_study_id>
    <nct_id>NCT04425200</nct_id>
  </id_info>
  <brief_title>Prevalence of HRR-related Genes Mutations and Prognosis in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients in Real World Setting</brief_title>
  <acronym>ZENSHIN</acronym>
  <official_title>Prevalence of HRR-related Genes Mutations and Prognosis in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients in Real World Setting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the prevalence of tissue homologous recombination&#xD;
      repair (HRR)-related gene mutations (positive/negative/Variant of uncertain significance&#xD;
      (VUS)), clinical outcome such as prostate-specific antigen-progression free survival&#xD;
      (PSA-PFS), overall survivals (OS) and treatment pattern in mCRPC patients.&#xD;
&#xD;
      &lt;Methods&gt; Study design: multi-center, prospective cohort study&#xD;
&#xD;
      Data Source(s):&#xD;
&#xD;
      In this study, 155 patients (expected recruitment patients: maximum 205 patients) will be&#xD;
      enrolled from approximately 20~30 sites in Japan. Study Population: mCRPC patients who&#xD;
      diagnosed between 2014 and 2018. Exposure(s): N.A Outcome(s): Prevalence of tissue&#xD;
      HRR-related gene mutations, clinical outcomes such as Over survival and PSA-PFS, Treatment&#xD;
      pattern&#xD;
&#xD;
      Sample Size Estimations:&#xD;
&#xD;
      The target population is 155 patients based on the prevalence of HRR-related genes (BRCA1,&#xD;
      BRCA2 and ATM) which is reported in previous global study (PROfound study).&#xD;
&#xD;
      Statistical Analysis:&#xD;
&#xD;
      This study is not intended to verify specific hypotheses, and the results are evaluated&#xD;
      descriptively. There is no plan of interim analyses before the final analysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 29, 2020</start_date>
  <completion_date type="Actual">December 18, 2020</completion_date>
  <primary_completion_date type="Actual">December 18, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of tissue HRR-related gene mutations</measure>
    <time_frame>Baseline</time_frame>
    <description>Calculate number and prevalence of each HRR-related gene mutation status (Positive/Negative/VUS), respectively. Prevalence will be accompanied by 95% Clopper-Pearson confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of each treatment pattern</measure>
    <time_frame>From index date(diagnosed as mCRPC) patients to December 31 2020</time_frame>
    <description>The number (%) of patients by treatment pattern in 1st line treatment, 2nd line, and 3rd line treatment after diagnosed as mCRPC, respectively, will be calculated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Patient's characteristics including stratified by tissue HRR-related gene mutations in mCRPC patients</measure>
    <time_frame>Baseline</time_frame>
    <description>Patient's characteristics will be summarized.</description>
  </other_outcome>
  <other_outcome>
    <measure>PSA50 response</measure>
    <time_frame>From index date(diagnosed as mCRPC) to december 31 2020</time_frame>
    <description>PSA50 response will be analysed based on baseline and nadir PSA value in each treatment.</description>
  </other_outcome>
  <enrollment type="Actual">205</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      An archived formalin fixed paraffin embedded (FFPE) sample, ten slides and 10 μm in thickness&#xD;
      on uncharged slide be used for HRR-related gene mutation testing in principle. And also, ten&#xD;
      10 μm slides is sent to Myriad with one 3-5 micron on a charge slide for the HE&#xD;
      staining(Hematoxylin and eosin staining) which is continuous with the slice for HRR-related&#xD;
      gene mutation. These contents include with a sample of &gt;25 mm2 in section area containing a&#xD;
      ≥30% tumor nuclei preferred (≥20% tumor nuclei accepted). If patients have some tumor samples&#xD;
      at multiple points, the latest sample is preferred to use HRR-related gene mutation testing.&#xD;
      And other tumor sample is acceptable to use HRR-related gene mutation testing if test is&#xD;
      failed.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The target population is mCRPC patients who diagnosed between 2014 and 2018 and be&#xD;
        confirmed to be succeeded HRR-related gene mutation analysis with archived primary or&#xD;
        metastatic tumor sample. As median of expected overall survival of mCRPC is 2.5 to 3 years&#xD;
        from diagnosis, follow up period is enough to measure outcomes including survival. The&#xD;
        baseline period is set to calculate overall survival and to detect clinical outcome at&#xD;
        least half. The patients will be enrolled consecutively to this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 20, Japanese men at the time of informed consent.&#xD;
&#xD;
          -  Patients who provided informed consent. If the patient has died, opt-out will be&#xD;
             applicable.&#xD;
&#xD;
          -  Patients who are diagnosed as mCRPC between January 1st in 2014 and December 31st in&#xD;
             2018.&#xD;
&#xD;
          -  Patients who have a FFPE tumor sample (primary or metastatic) with Formalin Neutral&#xD;
             Buffer Solution.&#xD;
&#xD;
          -  Patients which the investigator judges to secure the enough amount of tumor samples&#xD;
             for future laboratory test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have failed HRR-related gene mutation testing with the myChoice HRD plus&#xD;
             in screening period.&#xD;
&#xD;
          -  Patients who have an only FFPE primary tumor sample (primary or metastatic) with&#xD;
             unbuffered formalin including acidic formalin.&#xD;
&#xD;
          -  Patients who have taken an investigational medical product for prostate cancer from&#xD;
             Jan 1st , 2014 to Dec 31st 2020.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Nagoya City University Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagoya University Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hirosaki University Hospital</name>
      <address>
        <city>Hirosaki</city>
        <state>Aomori</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jikei University Kashiwa Hospital</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ehime University Hospital</name>
      <address>
        <city>Toon</city>
        <state>Ehime</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kure Medical Center</name>
      <address>
        <city>Kure</city>
        <state>Hiroshima</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hakodate Goryoukaku Hospital</name>
      <address>
        <city>Hakodate</city>
        <state>Hokkaido</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sapporo Medical University Hospital</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe City Medical Center General Hospital</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe University Hospital</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Tsukuba Hospital</name>
      <address>
        <city>Tsukuba</city>
        <state>Ibaraki</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanazawa University Hospital</name>
      <address>
        <city>Kanazawa</city>
        <state>Ishikawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kagawa University Hospital</name>
      <address>
        <city>Miki</city>
        <state>Kagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yokohama City University Hospital</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yokohama City University Medical Center</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nara Medical University Hospital</name>
      <address>
        <city>Kashihara</city>
        <state>Nara</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osakasayama</city>
        <state>Osaka</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Medical Center</name>
      <address>
        <city>Kawagoe</city>
        <state>Saitama</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tottori University Hospital</name>
      <address>
        <city>Yonago</city>
        <state>Tottori</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yamaguchi University Hospital</name>
      <address>
        <city>Ube</city>
        <state>Yamaguchi</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba University Hospital</name>
      <address>
        <city>Chiba</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gifu University Hospital</name>
      <address>
        <city>Gifu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyoto Prefectural University of Medicine</name>
      <address>
        <city>Kyoto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miyazaki Hospital</name>
      <address>
        <city>Miyazaki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Okayama University Hospital</name>
      <address>
        <city>Okayama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D081LR00002&amp;amp;attachmentIdentifier=af31e80d-5dae-46e5-accb-47980c519713&amp;amp;fileName=SYNOPSIS_for_Clin.govZENSHIN_20211112.pdf&amp;amp;versionIdentifier=</url>
    <description>Redacted CSR Synopsis</description>
  </link>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>November 30, 2021</last_update_submitted>
  <last_update_submitted_qc>November 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic castration resistant prostate cancer, BRCA1, BRCA2, ATM, Homologous recombination repair</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials/studies via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.</ipd_description>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </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/NCT04425200
org study id: D081LR00002
nct id: NCT04425200
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the prevalence of tissue homologous recombination
      repair (HRR)-related gene mutations (positive/negative/Variant of uncertain significance
      (VUS)), clinical outcome such as prostate-specific antigen-progression free survival
      (PSA-PFS), overall survivals (OS) and treatment pattern in mCRPC patients.

      <Methods> Study design: multi-center, prospective cohort study

      Data Source(s):

      In this study, 155 patients (expected recruitment patients: maximum 205 patients) will be
      enrolled from approximately 20~30 sites in Japan. Study Population: mCRPC patients who
      diagnosed between 2014 and 2018. Exposure(s): N.A Outcome(s): Prevalence of tissue
      HRR-related gene mutations, clinical outcomes such as Over survival and PSA-PFS, Treatment
      pattern

      Sample Size Estimations:

      The target population is 155 patients based on the prevalence of HRR-related genes (BRCA1,
      BRCA2 and ATM) which is reported in previous global study (PROfound study).

      Statistical Analysis:

      This study is not intended to verify specific hypotheses, and the results are evaluated
      descriptively. There is no plan of interim analyses before the final analysis.
observational model: Cohort
time perspective: Prospective
measure: Prevalence of tissue HRR-related gene mutations
time frame: Baseline
description: Calculate number and prevalence of each HRR-related gene mutation status (Positive/Negative/VUS), respectively. Prevalence will be accompanied by 95% Clopper-Pearson confidence intervals.
measure: Proportion of each treatment pattern
time frame: From index date(diagnosed as mCRPC) patients to December 31 2020
description: The number (%) of patients by treatment pattern in 1st line treatment, 2nd line, and 3rd line treatment after diagnosed as mCRPC, respectively, will be calculated.
measure: Patient's characteristics including stratified by tissue HRR-related gene mutations in mCRPC patients
time frame: Baseline
description: Patient's characteristics will be summarized.
measure: PSA50 response
time frame: From index date(diagnosed as mCRPC) to december 31 2020
description: PSA50 response will be analysed based on baseline and nadir PSA value in each treatment.
An archived formalin fixed paraffin embedded (FFPE) sample, ten slides and 10 μm in thickness
      on uncharged slide be used for HRR-related gene mutation testing in principle. And also, ten
      10 μm slides is sent to Myriad with one 3-5 micron on a charge slide for the HE
      staining(Hematoxylin and eosin staining) which is continuous with the slice for HRR-related
      gene mutation. These contents include with a sample of >25 mm2 in section area containing a
      ≥30% tumor nuclei preferred (≥20% tumor nuclei accepted). If patients have some tumor samples
      at multiple points, the latest sample is preferred to use HRR-related gene mutation testing.
      And other tumor sample is acceptable to use HRR-related gene mutation testing if test is
      failed.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
gender based: Yes
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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country: Japan
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D081LR00002&amp;attachmentIdentifier=af31e80d-5dae-46e5-accb-47980c519713&amp;fileName=SYNOPSIS_for_Clin.govZENSHIN_20211112.pdf&amp;versionIdentifier=
description: Redacted CSR Synopsis
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials/studies via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home