<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/NCT03753243</url>
  </required_header>
  <id_info>
    <org_study_id>15235</org_study_id>
    <nct_id>NCT03753243</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Pembrolizumab Plus Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer</brief_title>
  <official_title>Phase II Study of Neoadjuvant Pembrolizumab Plus Intensive Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mark Garzotto, MD</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Portland VA Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pembrolizumab will be administered at a dose of 200 mg will be administered as a 30 minute IV&#xD;
      infusion every 3 weeks. Enzalutamide will be administered at dose of 160 mg orally every day.&#xD;
      All patients will be required to have at least one high-risk criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators propose to study the effects of pembrolizumab combined with intensive&#xD;
      androgen receptor (AR) targeting prior to prostatectomy with extended pelvic lymph node&#xD;
      dissection in subjects with high-risk localized prostate cancer (HRLPC).&#xD;
&#xD;
      Trial Design- single arm, single-stage, open label Phase II of neoadjuvant immune-hormonal&#xD;
      therapy in high-risk localized prostate cancer.&#xD;
&#xD;
      Objectives To evaluate efficacy and safety of pembrolizumab combined with intensive AR&#xD;
      targeting prior to prostatectomy in subjects with high-risk localized prostate cancer&#xD;
      (HRLPC).&#xD;
&#xD;
      Primary Endpoint Pathologic complete response (pCR) defined as absence of detectable&#xD;
      malignant cells in the prostatectomy specimen evaluated by standard histologic techniques.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Anticipated">April 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 3, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>single arm, single-stage open label Phase II of neoadjuvant immune-hormonal therapy in high-risk Localized prostate cancer.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathologic Complete Response</measure>
    <time_frame>4 months</time_frame>
    <description>No cancer detected on pathology examination of prostatectomy specimen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment Related Adverse Events</measure>
    <time_frame>4 months + 30 days</time_frame>
    <description>Grade 3 or higher adverse event (AE) possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, Gonadotropin-releasing hormone (GNRH) agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune -related Adverse Events</measure>
    <time_frame>4 months + 30 days</time_frame>
    <description>Grade 2 or higher immune related AE possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, GNRH agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical Complete Response</measure>
    <time_frame>4 months</time_frame>
    <description>Prostate-Specific Antigen (PSA) &lt; 0.1 ng/mL prior to prostatectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Surgical Complications</measure>
    <time_frame>4 months</time_frame>
    <description>Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment will be planned for a total of 14 to 16 weeks. Pembrolizumab will be administered every 3 weeks via IV infusion with a dose of 200 mg per infusion. Enzalutamide will be given orally and dispensed to the patient on the date of their first infusion. The dosage of Enzalutamide will be 160 mg, administered once daily for approx. 16 weeks. GNRH agonist therapy will be administered as a standard of care therapy and will follow a standard dosage to maintain castrate levels.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide</intervention_name>
    <description>Patients will receive daily oral doses of study drug (enzalutamide 160 mg/day), which will be administered as four capsules/day to be taken at or near the same time each day.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Xtandi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          -  Capability to understand and comply with the protocol and signed informed consent&#xD;
             document.&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          -  Histologically confirmed, non-metastatic adenocarcinoma of the prostate&#xD;
&#xD;
          -  Prostatectomy with extended lymph node dissection planned as primary therapy&#xD;
&#xD;
          -  10 year or longer life expectancy based on other co-morbidities&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Scale.&#xD;
&#xD;
          -  Any one of the following three high risk features:&#xD;
&#xD;
               -  Gleason grade &gt; 8-10&#xD;
&#xD;
               -  PSA &gt; 20 ng/ml&#xD;
&#xD;
               -  Clinical stage T3a (resectable)&#xD;
&#xD;
          -  No evidence of metastases .&#xD;
&#xD;
          -  No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a&#xD;
             malignancy diagnosed ≥5 years ago).&#xD;
&#xD;
          -  Male subjects of childbearing potential must agree to use an adequate method of&#xD;
             contraception. Contraception, starting with the first dose of study therapy through&#xD;
             the time of surgery. Note: Abstinence is acceptable if this is the usual lifestyle and&#xD;
             preferred contraception for the subject.&#xD;
&#xD;
          -  Demonstrate adequate organ function, all screening labs should be performed within 30&#xD;
             days of treatment initiation.&#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>Mark Garzotto, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Portland VA Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wesley Stoller, MA</last_name>
    <phone>5032208262</phone>
    <phone_ext>54931</phone_ext>
    <email>stoller@ohsu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mark Garzotto, MD</last_name>
    <phone>5032208262</phone>
    <phone_ext>51982</phone_ext>
    <email>mark.garzotto@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>VA Portland Healthcare System</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wesley Stoller, MA</last_name>
      <phone>503-220-8262</phone>
      <phone_ext>54931</phone_ext>
      <email>stoller@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Mark Garzotto, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Portland VA Medical Center</investigator_affiliation>
    <investigator_full_name>Mark Garzotto, MD</investigator_full_name>
    <investigator_title>Director of Urologic Oncology</investigator_title>
  </responsible_party>
  <keyword>Neoadjuvant</keyword>
  <keyword>Programmed cell death protein 1 (PD-1)</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>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT03753243/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03753243
org study id: 15235
nct id: NCT03753243
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Pembrolizumab will be administered at a dose of 200 mg will be administered as a 30 minute IV
      infusion every 3 weeks. Enzalutamide will be administered at dose of 160 mg orally every day.
      All patients will be required to have at least one high-risk criteria.
The investigators propose to study the effects of pembrolizumab combined with intensive
      androgen receptor (AR) targeting prior to prostatectomy with extended pelvic lymph node
      dissection in subjects with high-risk localized prostate cancer (HRLPC).

      Trial Design- single arm, single-stage, open label Phase II of neoadjuvant immune-hormonal
      therapy in high-risk localized prostate cancer.

      Objectives To evaluate efficacy and safety of pembrolizumab combined with intensive AR
      targeting prior to prostatectomy in subjects with high-risk localized prostate cancer
      (HRLPC).

      Primary Endpoint Pathologic complete response (pCR) defined as absence of detectable
      malignant cells in the prostatectomy specimen evaluated by standard histologic techniques.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: single arm, single-stage open label Phase II of neoadjuvant immune-hormonal therapy in high-risk Localized prostate cancer.
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic Complete Response
time frame: 4 months
description: No cancer detected on pathology examination of prostatectomy specimen
measure: Treatment Related Adverse Events
time frame: 4 months + 30 days
description: Grade 3 or higher adverse event (AE) possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, Gonadotropin-releasing hormone (GNRH) agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy
measure: Immune -related Adverse Events
time frame: 4 months + 30 days
description: Grade 2 or higher immune related AE possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, GNRH agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy
measure: Biochemical Complete Response
time frame: 4 months
description: Prostate-Specific Antigen (PSA) < 0.1 ng/mL prior to prostatectomy
measure: Incidence of Surgical Complications
time frame: 4 months
description: Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.
arm group label: Intervention
arm group type: Experimental
description: Treatment will be planned for a total of 14 to 16 weeks. Pembrolizumab will be administered every 3 weeks via IV infusion with a dose of 200 mg per infusion. Enzalutamide will be given orally and dispensed to the patient on the date of their first infusion. The dosage of Enzalutamide will be 160 mg, administered once daily for approx. 16 weeks. GNRH agonist therapy will be administered as a standard of care therapy and will follow a standard dosage to maintain castrate levels.
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
arm group label: Intervention
other name: Keytruda
intervention type: Drug
intervention name: Enzalutamide
description: Patients will receive daily oral doses of study drug (enzalutamide 160 mg/day), which will be administered as four capsules/day to be taken at or near the same time each day.
arm group label: Intervention
other name: Xtandi
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Garzotto, MD
role: Principal Investigator
affiliation: Portland VA Medical Center
last name: Wesley Stoller, MA
phone: 5032208262
phone ext: 54931
email: stoller@ohsu.edu
last name: Mark Garzotto, MD
phone: 5032208262
phone ext: 51982
email: mark.garzotto@va.gov
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Portland VA Medical Center
investigator full name: Mark Garzotto, MD
investigator title: Director of Urologic Oncology
mesh term: Prostatic Neoplasms
mesh term: Pembrolizumab
sharing ipd: No
provided document: 