<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/NCT02213107</url>
  </required_header>
  <id_info>
    <org_study_id>53018</org_study_id>
    <nct_id>NCT02213107</nct_id>
  </id_info>
  <brief_title>Enzalutamide &amp; Dutasteride/Finasteride as 1st Line Treatment for Patients =/&gt; 65 Years Old With Prostate Cancer.</brief_title>
  <official_title>A Phase II Study of Enzalutamide Plus Dutasteride/Finasteride as First Line Treatment for Vulnerable Patients ≥ 65 Years With Systemic Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine the effect of enzalutamide and dutasteride or finasteride on the time to&#xD;
      prostatic-specific antigen level increase in patients age 65 or older.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to determine the effect of enzalutamide and&#xD;
      dutasteride or finasteride on the time to prostatic-specific antigen progression in patients&#xD;
      aged 65 or older receiving this combination as first line treatment for systemic prostate&#xD;
      cancer.&#xD;
&#xD;
      To determine the safety and toxicities of the study drug combination.&#xD;
&#xD;
      To determine the time to prostatic-specific antigen nadir from the start of study treatment&#xD;
      and to evaluate the absolute prostatic-specific antigen nadir as a result of the study drug&#xD;
      combination&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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 Progression Free Survival</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Time (months) from initiation of study treatment to PSA progression, defined by Prostate Cancer Clinical Trials Working Group 2 criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in lowest PSA level compared to baseline PSA level (Absolute PSA response)</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Change in lowest PSA level at follow up compared to baseline PSA level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA Nadir</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Time (months) to achieve the lowest PSA value compared to baseline PSA level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who experience a treatment-related adverse events.</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Adverse events will be defined according to CTCAE version 4.0.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in bone density</measure>
    <time_frame>Week 1 to Week 97</time_frame>
    <description>Change in bone density at week 97 compared to baseline bone density, measured using DEXA study</description>
  </other_outcome>
  <other_outcome>
    <measure>mean quality of life</measure>
    <time_frame>Week 1 to approximately 36 months</time_frame>
    <description>Change in quality of life score at follow up compared to baseline score, using FACT-P survey. The FACT-P survey is a 39 item questionnaire with a score that ranges from 0-156 with higher scores indicating better quality of life.</description>
  </other_outcome>
  <other_outcome>
    <measure>Comprehensive geriatric assessment domains</measure>
    <time_frame>Week 1 to approximately 36 months</time_frame>
    <description>Change in comprehensive geriatric assessment domains at follow up compared to baseline evaluation.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Enzalutamide and dutasteride or finasteride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Use of either 1. Enzalutamide and dutasteride or 2. Enzalutamide and finasteride.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide and Dutasteride or finasteride</intervention_name>
    <description>Use of either two oral drugs together&#xD;
Enzalutamide by mouth daily and dutasteride by mouth daily or&#xD;
Enzalutamide by mouth daily and finasteride by mouth daily</description>
    <arm_group_label>Enzalutamide and dutasteride or finasteride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Histologically or cytologically confirmed adenocarcinoma of the prostate without&#xD;
        neuroendocrine differentiation or small cell features.&#xD;
&#xD;
        Patients with systemic prostate cancer as defined by either a) hormonal naïve metastatic&#xD;
        prostate cancer with radiographic evidence of visceral or osseous metastasis or b)&#xD;
        biochemical recurrence prostate cancer that fulfills all of the following criteria:&#xD;
&#xD;
        A minimum of three rising prostatic-specific antigen levels with an interval of =/&gt; 1 week&#xD;
        between each test, The prostatic-specific antigen (PSA) value at the screening visit should&#xD;
        be =/&gt; 2 ng/ml prostatic-specific antigen doubling time ≤ 9 months.&#xD;
&#xD;
        Patients should be 65 years or older. Patients who are deemed &quot;not fit&quot; by comprehensive&#xD;
        geriatric assessment or at high risk for side effects as determined by the treating&#xD;
        physician. A case report form will be used to document the specifics of why each eligible&#xD;
        patient is not considered an ideal candidate.&#xD;
&#xD;
        Serum testosterone level &gt; 1.7 nmol/L (50 ng/dL) at the screening visit (non- castrate).&#xD;
&#xD;
        Patients could have received hormonal therapy as part of definitive treatment for previous&#xD;
        localized prostate cancer. However, they should be off any hormonal therapy for greater&#xD;
        than six months prior to entry to clinical trial.&#xD;
&#xD;
        Eastern Cooperative Oncology Group performance status of 0 to 2. Able to swallow the study&#xD;
        drug and comply with study requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Severe concurrent disease or infection that, in the judgment of the investigator, would&#xD;
        make the patient inappropriate for enrollment.&#xD;
&#xD;
        Known brain metastases. Brain imaging studies are not required for eligibility if the&#xD;
        patient has no neurologic signs or symptoms suggestive of brain metastasis. However, if&#xD;
        brain imaging studies are performed, they must be negative for disease.&#xD;
&#xD;
        Patient is receiving treatment for another active malignancy excluding localized cutaneous&#xD;
        squamous or basal cell carcinoma.&#xD;
&#xD;
        Prior treatment for systemic prostate cancer. Prior treatment with enzalutamide. Treatment&#xD;
        with androgen receptor antagonists (bicalutamide, flutamide, nilutamide,), ketoconazole,&#xD;
        abiraterone, finasteride, dutasteride, estrogens, or chemotherapy in an adjuvant setting&#xD;
        within 6 months of enrollment (Day 1 visit) or plans to initiate treatment with any of&#xD;
        these treatments.&#xD;
&#xD;
        Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to&#xD;
        initiate treatment with any of these treatments during the study period.&#xD;
&#xD;
        Use of herbal products that may decrease prostatic-specific antigen levels (e.g., saw&#xD;
        palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of&#xD;
        prednisone/prednisolone per day within 4 weeks of enrollment (Day 1 visit) or plans to&#xD;
        initiate treatment with any of these treatments during the study.&#xD;
&#xD;
        Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and&#xD;
        radioisotope therapy within 8 weeks of enrollment (Day 1 visit).&#xD;
&#xD;
        Participation in a previous clinical trial of an investigational agent that blocks androgen&#xD;
        synthesis within six months.&#xD;
&#xD;
        Participation in a previous clinical trial of enzalutamide. Use of an investigational agent&#xD;
        within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with an&#xD;
        investigational agent during the study.&#xD;
&#xD;
        Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of&#xD;
        the study the following medications known to lower the seizure threshold or increase or&#xD;
        decrease the bioavailability of the drug.&#xD;
&#xD;
        Concomitant use of strong or moderately strong Cytochrome P450 isozyme inducers:&#xD;
&#xD;
        Strong Cytochrome P450 isoenzyme 2C8 inhibitors like gemfibrozil, Strong Cytochrome P450&#xD;
        isoenzyme 2C8 inducers like Rifampin, Strong Cytochrome P450 isoenzyme 3A4 inhibitors like&#xD;
        Itraconazole, Aminophylline/theophylline, Atypical antipsychotics (e.g., clozapine,&#xD;
        olanzapine, risperidone, ziprasidone), Bupropion, Class IA and Class III antiarrhythmics&#xD;
        (e.g., amiodarone, bretylium, disopyramide, ibutilide, procainamide, quinidine, sotalol);&#xD;
        Dolasetron, Droperidol, Lithium, Macrolide antibiotics (e.g., erythromycin,&#xD;
        clarithromycin); Pethidine, Phenothiazine antipsychotics (e.g., chlorpromazine,&#xD;
        mesoridazine, thioridazine); Pimozide, Tricyclic and tetracyclic antidepressants(e.g.,&#xD;
        amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).&#xD;
&#xD;
        History of seizure, including any febrile seizure, loss of consciousness, or transient&#xD;
        ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may&#xD;
        predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma&#xD;
        with loss of consciousness requiring hospitalization).&#xD;
&#xD;
        Clinically significant cardiovascular disease including:&#xD;
&#xD;
        Myocardial infarction within 6 months, Uncontrolled angina within 3 months, Congestive&#xD;
        heart failure New York Heart Association class 3 or 4, or patients with history of&#xD;
        congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram&#xD;
        or multigated acquisition scan performed within 3 months results in a left ventricular&#xD;
        ejection fraction that is =/&gt; 45%, hypotension (systolic blood pressure &lt; 86 millimeters of&#xD;
        mercury [mmHg] or bradycardia with a heart rate &lt; 50 beats per minute, uncontrolled&#xD;
        hypertension as indicated by a resting systolic blood pressure of 170 mmHg or diastolic&#xD;
        blood pressure &gt; 105 mmHg at the Screening or Study Day 1 visit.&#xD;
&#xD;
        Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer&#xD;
        within last 3 months).&#xD;
&#xD;
        Major surgery within 4 weeks prior to enrollment (Day 1 visit). Absolute neutrophil count &lt;&#xD;
        1,500/µL, platelet count &lt; 100,000/µL, and hemoglobin &lt; 5.6 mmol/L (9 g/dL) at the&#xD;
        Screening visit; (NOTE: patients may not have received any growth factors or blood&#xD;
        transfusions within 7 days of the hematologic laboratory values obtained at the Screening&#xD;
        visit).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chunkit Fung, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconscin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</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 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Chunkit Fung</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>prostate</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>Finasteride</mesh_term>
    <mesh_term>Dutasteride</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/NCT02213107
org study id: 53018
nct id: NCT02213107
lead sponsor: 
has dmc: Yes
Determine the effect of enzalutamide and dutasteride or finasteride on the time to
      prostatic-specific antigen level increase in patients age 65 or older.
The primary objective of this study is to determine the effect of enzalutamide and
      dutasteride or finasteride on the time to prostatic-specific antigen progression in patients
      aged 65 or older receiving this combination as first line treatment for systemic prostate
      cancer.

      To determine the safety and toxicities of the study drug combination.

      To determine the time to prostatic-specific antigen nadir from the start of study treatment
      and to evaluate the absolute prostatic-specific antigen nadir as a result of the study drug
      combination
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PSA Progression Free Survival
time frame: up to approximately 36 months
description: Time (months) from initiation of study treatment to PSA progression, defined by Prostate Cancer Clinical Trials Working Group 2 criteria.
measure: Change in lowest PSA level compared to baseline PSA level (Absolute PSA response)
time frame: up to approximately 36 months
description: Change in lowest PSA level at follow up compared to baseline PSA level
measure: Time to PSA Nadir
time frame: up to approximately 36 months
description: Time (months) to achieve the lowest PSA value compared to baseline PSA level
measure: Number of participants who experience a treatment-related adverse events.
time frame: up to approximately 36 months
description: Adverse events will be defined according to CTCAE version 4.0.
measure: Change in bone density
time frame: Week 1 to Week 97
description: Change in bone density at week 97 compared to baseline bone density, measured using DEXA study
measure: mean quality of life
time frame: Week 1 to approximately 36 months
description: Change in quality of life score at follow up compared to baseline score, using FACT-P survey. The FACT-P survey is a 39 item questionnaire with a score that ranges from 0-156 with higher scores indicating better quality of life.
measure: Comprehensive geriatric assessment domains
time frame: Week 1 to approximately 36 months
description: Change in comprehensive geriatric assessment domains at follow up compared to baseline evaluation.
arm group label: Enzalutamide and dutasteride or finasteride
arm group type: Experimental
description: Use of either 1. Enzalutamide and dutasteride or 2. Enzalutamide and finasteride.
intervention type: Drug
intervention name: Enzalutamide and Dutasteride or finasteride
description: Use of either two oral drugs together
Enzalutamide by mouth daily and dutasteride by mouth daily or
Enzalutamide by mouth daily and finasteride by mouth daily
arm group label: Enzalutamide and dutasteride or finasteride
criteria: 
gender: All
minimum age: 65 Years
maximum age: 85 Years
healthy volunteers: No
last name: Chunkit Fung, M.D.
role: Principal Investigator
affiliation: University of Rochester
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Chunkit Fung
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms
mesh term: Finasteride
mesh term: Dutasteride