<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/NCT02208583</url>
  </required_header>
  <id_info>
    <org_study_id>E2014064</org_study_id>
    <nct_id>NCT02208583</nct_id>
  </id_info>
  <brief_title>Molecular Phenotype Changes and Personalized Treatment for CRPC</brief_title>
  <official_title>Exploratory Study of Molecular Phenotype Changes and Personalized Treatment for Patients With Castration Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tianjin Medical University Cancer Institute and Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To explore the molecular phenotypic changes and personalized treatment in&#xD;
      castration-resistant prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-center study to explore the molecular phenotypic changes in&#xD;
      castration-resistant prostate cancer by histopathological,immunohistochemical and molecular&#xD;
      analysis of cancer related genes in castration-resistant prostate cancer.After patient&#xD;
      eligibility is determined, tumor tissue will be acquired from archival or transurethral&#xD;
      resection or from re-biopsy specimens from patients with recurrence, visceral metastasis,&#xD;
      bone metastases. According to the molecular phenotypic changes, personalized treatment were&#xD;
      performed.&#xD;
&#xD;
      Participants will be screened with a full medical history and physical examination, blood and&#xD;
      urine tests, and tumor imaging studies. The tumor specimens at diagnosis of prostate cancer&#xD;
      should be needed for all the participants.&#xD;
&#xD;
      After assessing for the prostate specific antigen (PSA) level and the tumor molecular&#xD;
      phenotypic features,participants will be separated into different treatment groups:&#xD;
&#xD;
        1. Participants with &quot;AR dependent&quot; CRPC (generally with high PSA level and/or high AR&#xD;
           expression) and with druggable gene mutations will receive Docetaxel/prednisone+Target&#xD;
           drugs.&#xD;
&#xD;
        2. Participants with &quot;AR dependent&quot; CRPC (generally with high PSA level and/or high AR&#xD;
           expression) and without druggable gene mutations will receive Docetaxel/ Prednisone.&#xD;
&#xD;
        3. Participants with &quot;AR independent&quot; CRPC (generally without AR expression and/or rapid&#xD;
           progression with low PSA level) and with druggable gene mutations will receive&#xD;
           Cisplatin/Etoposide+Target drugs.&#xD;
&#xD;
        4. Participants with &quot;AR independent&quot; CRPC (generally without AR expression and/or rapid&#xD;
           progression with low PSA level) and without druggable gene mutations will receive&#xD;
           Cisplatin/Etoposide.&#xD;
&#xD;
      Participants with druggable gene mutations will receive the corresponding molecular targeted&#xD;
      drugs.&#xD;
&#xD;
      Participants with epidermal growth factor receptor (EGFR) gene mutation will receive a drug&#xD;
      called Gefitinib, which inhibits a protein called EGFR that is thought to be a key factor in&#xD;
      the development and progression of some cancers.&#xD;
&#xD;
      Participants with B-type Raf kinase (BRAF) gene mutations will receive a drug called&#xD;
      Vemurafenib, which inhibits a protein called mitogen-activated or extracellular&#xD;
      signal-regulated protein kinase kinase (MEK) that is thought to be a key factor in the&#xD;
      development and progression of some cancers.&#xD;
&#xD;
      Participants with v-akt murine thymoma viral oncogene homologue 1 (AKT1) gene mutations will&#xD;
      receive a drug called Celecoxib, which inhibits a protein called v-akt murine thymoma viral&#xD;
      oncogene homologue (AKT) that is thought to be a key factor in the development and&#xD;
      progression of some cancers.&#xD;
&#xD;
      Participants who have erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene mutation&#xD;
      will receive a drug called lapatinib, which inhibits some proteins that are thought to be key&#xD;
      factors in the development and progression of some cancers.&#xD;
&#xD;
      Participants with PDGFRA gene mutations will receive a drug called sunitinib, which inhibits&#xD;
      some proteins that are thought to be key factors in the development and progression of some&#xD;
      cancers.&#xD;
&#xD;
      Participants with PIK3CA gene mutations will receive a drug called Everolimus, which inhibits&#xD;
      a protein called AKT that is thought to be a key factor in the development and progression of&#xD;
      some cancers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>N/A</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Molecular phenotypic changes after acquired resistance of hormonal therapy</measure>
    <time_frame>24 months</time_frame>
    <description>The acquired resistance criteria is based on the european criteria for castration resistant prostate cancer.The molecular phenotypic changes including the following observations:1.histopathologic analysis for rebiopsy pathology in CRPC;2.Immunohistochemical staining for androgen receptor(AR),Ki-67,cluster of differentiation 56(CD56),Syn,P53, AURKA,N-myc,retinoblastoma susceptibility(RB), E-cadherin, vimentin;3.Targeting exom sequencing by TruSeq Amplicon Cancer Panel(TSACP) including the hotspot mutation for 48 cancer related genes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>clinical progression free survival(cPFS)</measure>
    <time_frame>24months</time_frame>
    <description>cPFS is defined as the time from the start of treatment to disease progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival(OS)</measure>
    <time_frame>24 months</time_frame>
    <description>OS is defined as the time the time from the start of treatment to death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The relationship between molecular phenotypic changes and OS</measure>
    <time_frame>24 months</time_frame>
    <description>The relationship between molecular phenotypic changes and OS means how the molecular phenotypic changes affects OS.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Hormone Refractory Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>AR dependent CRPC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Assignment to Treatment Group based on druggable gene mutations analysis:&#xD;
CRPC patients without druggable gene mutations: Docetaxel &amp; Prednisone; CRPC patients with druggable gene mutations: DP &amp; Targeted drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR independent CRPC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Assignment to Treatment Group based on druggable gene mutations analysis:&#xD;
CRPC patients without druggable gene mutations: cisplatin &amp; Etoposide; CRPC patients with druggable gene mutations: EP &amp; Targeted drugs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel &amp; Prednisone</intervention_name>
    <description>Docetaxel &amp; Prednisone: Docetaxel 75mg/m2，d1;Prednisone 5mg，bid，d1-21</description>
    <arm_group_label>AR dependent CRPC</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DP &amp; Targeted drugs</intervention_name>
    <description>Docetaxel 75mg/m2，d1; Prednisone 5mg，bid，d1-21;Targeted drugs for PO. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus</description>
    <arm_group_label>AR dependent CRPC</arm_group_label>
    <other_name>Targeted drugs for PO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin &amp; Etoposide</intervention_name>
    <description>cisplatin &amp; Etoposide:cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3</description>
    <arm_group_label>AR independent CRPC</arm_group_label>
    <other_name>cisplatin and Etoposide for injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EP &amp; Targeted drugs</intervention_name>
    <description>cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3; Targeted drugs for po. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus</description>
    <arm_group_label>AR independent CRPC</arm_group_label>
    <other_name>Targeted drugs for po</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 Years and older;&#xD;
&#xD;
          2. patients with CRPC according to European Association of Urology diagnostic criteria ;&#xD;
&#xD;
          3. vital organs functions including bone marrow, heart, liver, kidney are normal;&#xD;
&#xD;
          4. complete pathological specimens including newly diagnosed with prostate cancer and&#xD;
             disease progress to CRPC: ① biopsies or surgical specimens (tissue bank or wax block&#xD;
             preserved specimens) at diagnosis ; ② re-biopsy specimens,transurethral prostatectomy&#xD;
             (TURP) specimens, metastases palliative surgical specimens (tissue bank or wax block&#xD;
             preserved specimens) after progress to CRPC; ③ amount sufficient sample for DNA&#xD;
             extraction and quality control by up to standard (a) Sample type: None RNA degradation&#xD;
             and pollution-free DNA samples; (b) the amount of the sample (single): ≥ 250ng (using&#xD;
             agilent liquid platform); (c) sample concentration: ≥ 50 ng / μl (using agilent liquid&#xD;
             platform); (d) sample purity: OD 260/280 = 1.8 ~ 2.0 );&#xD;
&#xD;
          5. Then we perform following tests when patients meet the above criteria: ①Histological&#xD;
             analysis: Hematoxylin-eosin(HE) staining ②immunohistochemistry(IHC) staining ③ 48&#xD;
             carcinomas associated exon sequencing&#xD;
&#xD;
          6. After performing the above test, enter treatment group ① Docetaxel &amp; Prednisone(DP) :&#xD;
             with high PSA and no gene mutation; ② DP + targeted drugs: with high PSA and gene&#xD;
             mutations; ③ cisplatin &amp; Etoposide(EP) : low PSA and no gene mutation; ④ EP + targeted&#xD;
             drug: Low PSA and gene mutations.&#xD;
&#xD;
          7. All patients enrolled in draw peripheral blood samples 7.5ml and detect circulating&#xD;
             tumor cells (CTC) , monitoring efficacy.&#xD;
&#xD;
        8. Willing and able to comply with the program during the study period. 9 before entering&#xD;
        clinical trials to provide written informed consent form, and the patient has to know you&#xD;
        can withdraw from the study at any time in the study, and without any loss.&#xD;
&#xD;
        10. Agrees to provide blood and tissue specimens. 11 expected survival of&gt; 6 months&#xD;
        12.Karnofsky performance status (KPS)&gt; 60; Eastern Cooperative Oncology Group(ECOG) score&#xD;
        0-2 13 signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. other cancers&#xD;
&#xD;
          2. cognitive inability and mental abnormalities&#xD;
&#xD;
          3. other serious disease or condition&#xD;
&#xD;
               -  severe, uncontrolled internal medicine and infectious diseases&#xD;
&#xD;
               -  severe digestive disorder can not control&#xD;
&#xD;
               -  severe electrolyte imbalance&#xD;
&#xD;
               -  active disseminated intravascular coagulation&#xD;
&#xD;
               -  major organ failure, such as decompensated heart, lung, liver, kidney failure&#xD;
&#xD;
               -  peripheral neuropathy symptoms, NCI grade&gt; Ⅱ degree&#xD;
&#xD;
          4. can not tolerate chemotherapy or refuse chemotherapy&#xD;
&#xD;
          5. using the other test drug or participate other clinical trials&#xD;
&#xD;
          6. can not oral drugs&#xD;
&#xD;
          7. receiving chemotherapy, biological therapy, or other anti-cancer medicine intervals&#xD;
             less than 4 weeks&#xD;
&#xD;
          8. Researchers believe patients unsuitable (compliance, we should not follow-up)&#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>Wang HaiTao, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wang HaiTao, Ph.D</last_name>
    <phone>+86-18630955984</phone>
    <email>peterrock2000@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wang HaiTao, Ph.D</last_name>
      <phone>+86-18630955984</phone>
      <email>peterrock2000@126.com</email>
    </contact>
    <investigator>
      <last_name>Wang HaiTao, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>August 4, 2014</last_update_submitted>
  <last_update_submitted_qc>August 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Molecular phenotypic；CRPC; personalized treatment</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>Cisplatin</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Etoposide phosphate</mesh_term>
  </intervention_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/NCT02208583
org study id: E2014064
nct id: NCT02208583
lead sponsor: 
has dmc: Yes
To explore the molecular phenotypic changes and personalized treatment in
      castration-resistant prostate cancer.
This is a multi-center study to explore the molecular phenotypic changes in
      castration-resistant prostate cancer by histopathological,immunohistochemical and molecular
      analysis of cancer related genes in castration-resistant prostate cancer.After patient
      eligibility is determined, tumor tissue will be acquired from archival or transurethral
      resection or from re-biopsy specimens from patients with recurrence, visceral metastasis,
      bone metastases. According to the molecular phenotypic changes, personalized treatment were
      performed.

      Participants will be screened with a full medical history and physical examination, blood and
      urine tests, and tumor imaging studies. The tumor specimens at diagnosis of prostate cancer
      should be needed for all the participants.

      After assessing for the prostate specific antigen (PSA) level and the tumor molecular
      phenotypic features,participants will be separated into different treatment groups:

        1. Participants with "AR dependent" CRPC (generally with high PSA level and/or high AR
           expression) and with druggable gene mutations will receive Docetaxel/prednisone+Target
           drugs.

        2. Participants with "AR dependent" CRPC (generally with high PSA level and/or high AR
           expression) and without druggable gene mutations will receive Docetaxel/ Prednisone.

        3. Participants with "AR independent" CRPC (generally without AR expression and/or rapid
           progression with low PSA level) and with druggable gene mutations will receive
           Cisplatin/Etoposide+Target drugs.

        4. Participants with "AR independent" CRPC (generally without AR expression and/or rapid
           progression with low PSA level) and without druggable gene mutations will receive
           Cisplatin/Etoposide.

      Participants with druggable gene mutations will receive the corresponding molecular targeted
      drugs.

      Participants with epidermal growth factor receptor (EGFR) gene mutation will receive a drug
      called Gefitinib, which inhibits a protein called EGFR that is thought to be a key factor in
      the development and progression of some cancers.

      Participants with B-type Raf kinase (BRAF) gene mutations will receive a drug called
      Vemurafenib, which inhibits a protein called mitogen-activated or extracellular
      signal-regulated protein kinase kinase (MEK) that is thought to be a key factor in the
      development and progression of some cancers.

      Participants with v-akt murine thymoma viral oncogene homologue 1 (AKT1) gene mutations will
      receive a drug called Celecoxib, which inhibits a protein called v-akt murine thymoma viral
      oncogene homologue (AKT) that is thought to be a key factor in the development and
      progression of some cancers.

      Participants who have erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene mutation
      will receive a drug called lapatinib, which inhibits some proteins that are thought to be key
      factors in the development and progression of some cancers.

      Participants with PDGFRA gene mutations will receive a drug called sunitinib, which inhibits
      some proteins that are thought to be key factors in the development and progression of some
      cancers.

      Participants with PIK3CA gene mutations will receive a drug called Everolimus, which inhibits
      a protein called AKT that is thought to be a key factor in the development and progression of
      some cancers.
allocation: Non-Randomized
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Molecular phenotypic changes after acquired resistance of hormonal therapy
time frame: 24 months
description: The acquired resistance criteria is based on the european criteria for castration resistant prostate cancer.The molecular phenotypic changes including the following observations:1.histopathologic analysis for rebiopsy pathology in CRPC;2.Immunohistochemical staining for androgen receptor(AR),Ki-67,cluster of differentiation 56(CD56),Syn,P53, AURKA,N-myc,retinoblastoma susceptibility(RB), E-cadherin, vimentin;3.Targeting exom sequencing by TruSeq Amplicon Cancer Panel(TSACP) including the hotspot mutation for 48 cancer related genes.
measure: clinical progression free survival(cPFS)
time frame: 24months
description: cPFS is defined as the time from the start of treatment to disease progression.
measure: Overall Survival(OS)
time frame: 24 months
description: OS is defined as the time the time from the start of treatment to death.
measure: The relationship between molecular phenotypic changes and OS
time frame: 24 months
description: The relationship between molecular phenotypic changes and OS means how the molecular phenotypic changes affects OS.
arm group label: AR dependent CRPC
arm group type: Active Comparator
description: Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: Docetaxel & Prednisone; CRPC patients with druggable gene mutations: DP & Targeted drugs
arm group label: AR independent CRPC
arm group type: Active Comparator
description: Assignment to Treatment Group based on druggable gene mutations analysis:
CRPC patients without druggable gene mutations: cisplatin & Etoposide; CRPC patients with druggable gene mutations: EP & Targeted drugs
intervention type: Drug
intervention name: Docetaxel & Prednisone
description: Docetaxel & Prednisone: Docetaxel 75mg/m2，d1;Prednisone 5mg，bid，d1-21
arm group label: AR dependent CRPC
other name: Taxotere
intervention type: Drug
intervention name: DP & Targeted drugs
description: Docetaxel 75mg/m2，d1; Prednisone 5mg，bid，d1-21;Targeted drugs for PO. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus
arm group label: AR dependent CRPC
other name: Targeted drugs for PO
intervention type: Drug
intervention name: cisplatin & Etoposide
description: cisplatin & Etoposide:cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3
arm group label: AR independent CRPC
other name: cisplatin and Etoposide for injection
intervention type: Drug
intervention name: EP & Targeted drugs
description: cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3; Targeted drugs for po. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus
arm group label: AR independent CRPC
other name: Targeted drugs for po
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wang HaiTao, Ph.D
role: Principal Investigator
affiliation: Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital
last name: Wang HaiTao, Ph.D
phone: +86-18630955984
email: peterrock2000@126.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Cisplatin
mesh term: Docetaxel
mesh term: Etoposide
mesh term: Etoposide phosphate