<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/NCT03017794</url>
  </required_header>
  <id_info>
    <org_study_id>16-008637</org_study_id>
    <secondary_id>NCI-2023-00596</secondary_id>
    <nct_id>NCT03017794</nct_id>
  </id_info>
  <brief_title>Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy</brief_title>
  <official_title>Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to test a hypothesis that a greater increase in serum chromogranin A&#xD;
      (CgA) after a definitive radiotherapy (RT) with or without androgen deprivation therapy (ADT)&#xD;
      is associated with a higher risk of prostate cancer recurrence after RT. Serum CgA level is&#xD;
      measured before the start of RT and/or the start of neoadjuvant ADT for patients undergoing a&#xD;
      definitive RT with or without ADT. CgA is also measured at various pre-defined post-RT time&#xD;
      points. The study will analyze the followings: 1. Change in CgA level at various pre-defined&#xD;
      post-RT time points from the baseline, 2. Correlation between the extent of post-therapy CgA&#xD;
      change and Gleason score of malignancy, 3. Correlation between the extent of post-therapy CgA&#xD;
      change and treatment outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuroendocrine differentiation (NED) in prostate cancer is a well-recognized phenotypic&#xD;
      change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like)&#xD;
      cells. Accumulated evidences have suggested that the prevalence of NE-like cells is&#xD;
      associated with disease progression and poor prognosis.&#xD;
&#xD;
      NED can be induced by a therapeutic agent. Such therapeutic agents include RT and ADT.&#xD;
      RT-induced NED represents a novel pathway by which prostate cancer cells survive radiotherapy&#xD;
      and contribute to treatment failure and tumor recurrence. Chromogranin A is the serum&#xD;
      biomarker for NED and correlates well with CgA-positive staining in biopsy specimens. It has&#xD;
      been reported that elevated serum CgA is associated with poor therapeutic response,&#xD;
      androgen-independent growth, and biochemical recurrence.&#xD;
&#xD;
      The study tests whether the extent of serum CgA increase by RT +/- ADT, which reflects&#xD;
      radiation-induced NED, is correlated with the risk of prostate cancer recurrence following RT&#xD;
      and a Gleason score of prostate carcinoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 4, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Correlate the extent of post-RT CgA change with Gleason score of malignancy</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlate the extent of post-RT CgA change with treatment outcome, using biochemical recurrence as an endpoint</measure>
    <time_frame>60 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Examine the extent of CgA change at various post-RT time points</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Examine the effect of ADT on CgA level for patients receiving RT + ADT, and Compare the extent of post-therapy CgA change between patients receiving RT alone and those undergoing RT + ADT</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the extent of post-therapy CgA change between patients receiving photon-based RT and those undergoing proton-based RT</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">125</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Gleason score 6 or less</arm_group_label>
    <description>Prostate adenocarcinoma with Gleason score 6 or less</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gleason score 7</arm_group_label>
    <description>Prostate adenocarcinoma with Gleason score 7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gleason score 8 -10</arm_group_label>
    <description>Prostate adenocarcinoma with Gleason score 8 -10</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients that are to receive either definitive RT +/- ADT as a primary therapy or salvage&#xD;
        RT +/- ADT as a salvage therapy for a biochemical relapse with local recurrence in the&#xD;
        prostatic fossa following a radical prostatectomy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinically localized prostate carcinoma, T1-T4 N0M0, any Gleason Score, any&#xD;
             prostate-specific antigen (PSA), or Biochemical relapse with clinically suspicious&#xD;
             (based on MRI or clinical examination) or biopsy-proven local recurrence in the&#xD;
             prostatic fossa after a radical prostatectomy&#xD;
&#xD;
          -  ≥18 years old&#xD;
&#xD;
          -  Histologic diagnosis of prostate adenocarcinoma&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Biochemical relapse alone without clinically suspicious (i.e. no suspicious lesion on&#xD;
             MRI of the prostatic bed) or biopsy-proven local recurrence in the prostatic fossa&#xD;
&#xD;
          -  Regional pelvic node metastasis (N1)&#xD;
&#xD;
          -  Distant metastasis (M1)&#xD;
&#xD;
          -  Concurrent or previous cytotoxic medications&#xD;
&#xD;
          -  Medical or psychological conditions that in the opinion of the investigator would not&#xD;
             allow 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>C. Richard Choo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clinical Trials Referral Office</last_name>
    <phone>855-776-0015</phone>
  </overall_contact>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 20, 2023</last_update_submitted>
  <last_update_submitted_qc>January 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Chunhee Richard Choo, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Radiotherapy</keyword>
  <keyword>Chromogranin A</keyword>
  <keyword>Neuroendocrine differentiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Recurrence</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/NCT03017794
org study id: 16-008637
secondary id: NCI-2023-00596
nct id: NCT03017794
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a pilot study to test a hypothesis that a greater increase in serum chromogranin A
      (CgA) after a definitive radiotherapy (RT) with or without androgen deprivation therapy (ADT)
      is associated with a higher risk of prostate cancer recurrence after RT. Serum CgA level is
      measured before the start of RT and/or the start of neoadjuvant ADT for patients undergoing a
      definitive RT with or without ADT. CgA is also measured at various pre-defined post-RT time
      points. The study will analyze the followings: 1. Change in CgA level at various pre-defined
      post-RT time points from the baseline, 2. Correlation between the extent of post-therapy CgA
      change and Gleason score of malignancy, 3. Correlation between the extent of post-therapy CgA
      change and treatment outcome.
Neuroendocrine differentiation (NED) in prostate cancer is a well-recognized phenotypic
      change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like)
      cells. Accumulated evidences have suggested that the prevalence of NE-like cells is
      associated with disease progression and poor prognosis.

      NED can be induced by a therapeutic agent. Such therapeutic agents include RT and ADT.
      RT-induced NED represents a novel pathway by which prostate cancer cells survive radiotherapy
      and contribute to treatment failure and tumor recurrence. Chromogranin A is the serum
      biomarker for NED and correlates well with CgA-positive staining in biopsy specimens. It has
      been reported that elevated serum CgA is associated with poor therapeutic response,
      androgen-independent growth, and biochemical recurrence.

      The study tests whether the extent of serum CgA increase by RT +/- ADT, which reflects
      radiation-induced NED, is correlated with the risk of prostate cancer recurrence following RT
      and a Gleason score of prostate carcinoma.
observational model: Cohort
time perspective: Prospective
measure: Correlate the extent of post-RT CgA change with Gleason score of malignancy
time frame: 18 months
measure: Correlate the extent of post-RT CgA change with treatment outcome, using biochemical recurrence as an endpoint
time frame: 60 months
measure: Examine the extent of CgA change at various post-RT time points
time frame: 18 months
measure: Examine the effect of ADT on CgA level for patients receiving RT + ADT, and Compare the extent of post-therapy CgA change between patients receiving RT alone and those undergoing RT + ADT
time frame: 18 months
measure: Compare the extent of post-therapy CgA change between patients receiving photon-based RT and those undergoing proton-based RT
time frame: 24 months
arm group label: Gleason score 6 or less
description: Prostate adenocarcinoma with Gleason score 6 or less
arm group label: Gleason score 7
description: Prostate adenocarcinoma with Gleason score 7
arm group label: Gleason score 8 -10
description: Prostate adenocarcinoma with Gleason score 8 -10
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: C. Richard Choo, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Clinical Trials Referral Office
phone: 855-776-0015
facility: 
status: Recruiting
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Chunhee Richard Choo, M.D.
investigator title: Principal Investigator
mesh term: Recurrence