<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/NCT03246347</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00081385</org_study_id>
    <secondary_id>LCI-GU-PRO-ADDE-001</secondary_id>
    <secondary_id>Pro00018087</secondary_id>
    <nct_id>NCT03246347</nct_id>
  </id_info>
  <brief_title>A Trial of Androgen Deprivation, Docetaxel, and Enzalutamide for Metastatic Prostate Cancer</brief_title>
  <official_title>A Phase II Trial of Androgen Deprivation, Docetaxel and Enzalutamide in Patients With Metastatic Hormone Sensitive Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medivation, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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>
      This is a study with the combination of androgen deprivation therapy (ADT) and docetaxel with&#xD;
      the addition of enzalutamide in the treatment of subjects with metastatic prostate cancer.&#xD;
      The purpose of this study is to assess if ADT + docetaxel + enzalutamide is well tolerated&#xD;
      and demonstrates improved efficacy compared to ADT + docetaxel.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, single arm, phase II trial designed to evaluate the 12 month PSA&#xD;
      complete response rate in patients with metastatic hormone sensitive prostate cancer treated&#xD;
      with ADT, docetaxel and enzalutamide. The primary endpoint of this study will be 12-month PSA&#xD;
      complete response rate, which will be assessed against a contemporary historical control rate&#xD;
      for the combination of ADT and docetaxel alone in the metastatic hormone naive setting. The&#xD;
      study will be conducted at all participating sites across North and South Carolina within the&#xD;
      Levine Cancer Institute network. Enrollment is anticipated to be completed within 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 23, 2017</start_date>
  <completion_date type="Anticipated">March 2028</completion_date>
  <primary_completion_date type="Actual">September 1, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PSA complete response rate</measure>
    <time_frame>12 month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serologic response rate</measure>
    <time_frame>Duration of study participation, an average of 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic response rate</measure>
    <time_frame>Duration of study participation, an average of 2-3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to castrate resistance</measure>
    <time_frame>Duration of study participation, an average of 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serologic progression free survival</measure>
    <time_frame>Duration of study participation, an average of 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>radiographic progression free survival</measure>
    <time_frame>Duration of study participation, an average of 2-3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>Duration of study participation, an average of 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to treatment failure</measure>
    <time_frame>Duration of study participation, an average of 2-3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Duration of study participation, an average of 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Docetaxel + Enzalutamide + Androgen Deprivation Therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADT+Docetaxel+Enzalutamide</intervention_name>
    <description>combination therapy as listed above</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>Taxotere</other_name>
    <other_name>Xtandi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without&#xD;
             evidence of small cell carcinoma or greater than 50% neuroendocrine differentiation.&#xD;
             Metastatic disease must be present including soft tissue, and/or bone metastases OR&#xD;
             nonregional lymph node involvement prior to study enrollment. If the subject has&#xD;
             regional lymph node involvement, there must be at least one additional site of disease&#xD;
             including visceral, non-regional nodal or skeletal metastases.&#xD;
&#xD;
          -  ADT with surgical castration with bilateral orchiectomy or medical castration with&#xD;
             LHRH agonist or LHRH antagonist therapy may have been initiated no greater than 112&#xD;
             days (16 weeks) prior to enrollment date. Subjects who initiated ADT prior to consent,&#xD;
             are not eligible if PSA has risen ≥ 25% and ≥ 2 ng/ml above nadir value since&#xD;
             initiation of ADT prior to consent.&#xD;
&#xD;
          -  At least one PSA level of ≥ 5 ng/ml within 90 days prior to consent.&#xD;
&#xD;
          -  Prior ADT for non-metastatic disease with LHRH agonist or LHRH antagonist therapy in&#xD;
             the neoadjuvant/adjuvant setting is permitted if:&#xD;
&#xD;
               1. Total duration of therapy did not exceed 36 months&#xD;
&#xD;
               2. 6 months have elapsed since completion of therapy prior to consent,&#xD;
&#xD;
               3. Serum testosterone &gt; 50 ng/dl within 28 days prior to reinitiation of ADT for&#xD;
                  metastatic disease&#xD;
&#xD;
               4. Prior ADT for non-metastatic disease must have accompanied definitive local&#xD;
                  therapy for curative intent.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  ECOG performance status 0-2.&#xD;
&#xD;
          -  Adequate liver function: AST and ALT &lt;1.5x upper limit of normal, total bilirubin &lt; 1x&#xD;
             upper limit of normal.&#xD;
&#xD;
          -  Adequate bone marrow function: Platelets &gt;100,000 cells/mm3, Hemoglobin &gt; 8.0g/dL and&#xD;
             ANC &gt; 1,500 cells/mm3.&#xD;
&#xD;
          -  Adequate renal function with a creatinine clearance (based on Cockcroft-Gault formula)&#xD;
             ≥ 30 mL/min.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Able to swallow and retain oral medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Personal history of seizure.&#xD;
&#xD;
          -  Personal history of conditions that may predispose to seizure activity including&#xD;
             cortical cerebrovascular accident or brain trauma.&#xD;
&#xD;
          -  Known central nervous system metastases, including involvement of brain parenchyma and&#xD;
             leptomeninges.&#xD;
&#xD;
          -  Personal history of any condition that may impair absorption of enzalutamide.&#xD;
&#xD;
          -  Prior or current therapy with ketoconazole, abiraterone, enzalutamide, apalutamide&#xD;
             (ARN-509, JNJ-56021927), darolutamide (ODM-201, BAY1841788) or cytotoxic chemotherapy&#xD;
             such as docetaxel, cabazitaxel, cyclophosphamide.&#xD;
&#xD;
          -  Prior therapy with bicalutamide, nilutamide or flutamide within 14 days of enrollment.&#xD;
&#xD;
          -  Within 28 days of major surgery and/or lack of recovery from prior surgical procedure&#xD;
             or 14 days of palliative radiation prior to enrollment.&#xD;
&#xD;
          -  Prior or current therapy with an investigational agent for metastatic prostate cancer.&#xD;
&#xD;
          -  Known hypersensitivity to drugs formulated with polysorbate 80.&#xD;
&#xD;
          -  Personal history of posterior reversible encephalopathy syndrome.&#xD;
&#xD;
          -  CTCAE version 4.0 grade 2-4 peripheral sensory neuropathy.&#xD;
&#xD;
          -  Human immunodeficiency virus infection or active hepatitis B or C infection.&#xD;
&#xD;
          -  Uncontrolled and current illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements in the opinion of the investigator.&#xD;
&#xD;
          -  Presence of any of the following within the previous 3 months prior to enrollment:&#xD;
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass&#xD;
             graft, congestive heart failure, or cerebrovascular accident including transient&#xD;
             ischemic attack.&#xD;
&#xD;
          -  History of an additional active malignancy within 12 months prior to the date of&#xD;
             consent (except non-melanoma skin cancer).&#xD;
&#xD;
          -  Current use of strong CYP2C8 inhibitors, CYP3A4 inducers or CYP3A4, CYP2C9 or CYP2C19&#xD;
             substrates with a narrow therapeutic range as listed in Section 7.2.1.&#xD;
&#xD;
          -  Any condition that requires the use of prednisone &gt; 10mg daily, or equivalent daily&#xD;
             glucocorticoid dose, for greater than 14 days&#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>Earle Burgess, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Docetaxel</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 6, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03246347/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>August 25, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03246347
org study id: IRB00081385
secondary id: LCI-GU-PRO-ADDE-001
secondary id: Pro00018087
nct id: NCT03246347
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a study with the combination of androgen deprivation therapy (ADT) and docetaxel with
      the addition of enzalutamide in the treatment of subjects with metastatic prostate cancer.
      The purpose of this study is to assess if ADT + docetaxel + enzalutamide is well tolerated
      and demonstrates improved efficacy compared to ADT + docetaxel.
This is a single center, single arm, phase II trial designed to evaluate the 12 month PSA
      complete response rate in patients with metastatic hormone sensitive prostate cancer treated
      with ADT, docetaxel and enzalutamide. The primary endpoint of this study will be 12-month PSA
      complete response rate, which will be assessed against a contemporary historical control rate
      for the combination of ADT and docetaxel alone in the metastatic hormone naive setting. The
      study will be conducted at all participating sites across North and South Carolina within the
      Levine Cancer Institute network. Enrollment is anticipated to be completed within 24 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PSA complete response rate
time frame: 12 month
measure: Serologic response rate
time frame: Duration of study participation, an average of 2 years
measure: Radiographic response rate
time frame: Duration of study participation, an average of 2-3 years
measure: Time to castrate resistance
time frame: Duration of study participation, an average of 2 years
measure: serologic progression free survival
time frame: Duration of study participation, an average of 2 years
measure: radiographic progression free survival
time frame: Duration of study participation, an average of 2-3 years
measure: overall survival
time frame: Duration of study participation, an average of 5 years
measure: time to treatment failure
time frame: Duration of study participation, an average of 2-3 years
measure: Treatment-related adverse events as assessed by CTCAE v4.0
time frame: Duration of study participation, an average of 5 years
arm group label: Single Arm
arm group type: Experimental
description: Docetaxel + Enzalutamide + Androgen Deprivation Therapy
intervention type: Drug
intervention name: ADT+Docetaxel+Enzalutamide
description: combination therapy as listed above
arm group label: Single Arm
other name: Taxotere
other name: Xtandi
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Earle Burgess, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Docetaxel
provided document: 
submitted: August 25, 2023