<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/NCT03829930</url>
  </required_header>
  <id_info>
    <org_study_id>GWCC 1000</org_study_id>
    <nct_id>NCT03829930</nct_id>
  </id_info>
  <brief_title>Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer</brief_title>
  <official_title>A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>George Washington University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>George Washington University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine the safety and tolerability of Entinostat in combination with Enzalutamide in&#xD;
      metastatic castrate resistant prostate cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed to determine the safety and tolerability of Entinostat with&#xD;
      Enzalutamide for treatment of patients with castration-resistant prostate cancer. There will&#xD;
      be two dose levels of Entinostat in combination with same dose of Enzalutamide. Patients will&#xD;
      be followed during treatment and 1 month post discontinuation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor discontinued the drug&#xD;
  </why_stopped>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Actual">September 1, 2020</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>3+3 Design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of a suitable dose of Entinostat in combination with Enzalutamide</measure>
    <time_frame>18 months</time_frame>
    <description>Number of participants who experience an adverse event assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>3 years</time_frame>
    <description>Number of participants who survive without disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs</measure>
    <time_frame>18 months</time_frame>
    <description>Analysis of immunomodulatory effects of Entinostat</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Entinostat and Enzalutamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Entinostat and Enzalutamide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entinostat</intervention_name>
    <description>Entinostat is formulated for oral administration. A food effect is evident for entinostat; exposure is significantly reduced when entinostat is administered with a high fat meal. Accordingly, entinostat is to be administered on an empty stomach, at least 1 hour before and 2 hours after a meal. Entinostat tablets should not be split, crushed, or chewed. Consult the individual clinical protocols for specific dosing instructions.&#xD;
Dose level 1: 3mg PO weekly. Dose level 2: 5mg PO weekly.</description>
    <arm_group_label>Entinostat and Enzalutamide</arm_group_label>
    <other_name>SYND-275 amd MS-275</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide</intervention_name>
    <description>Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.</description>
    <arm_group_label>Entinostat and Enzalutamide</arm_group_label>
    <other_name>MDV3100</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Each patient must meet all of the following inclusion criteria to be enrolled in the study:&#xD;
&#xD;
          -  Age &gt;/= 18 years and are capable of giving informed consent. Voluntary written&#xD;
             informed consent before performance of any study-related procedure not part of normal&#xD;
             medical care, with the understanding that consent may be withdrawn by the subject at&#xD;
             any time without prejudice to future medical care.&#xD;
&#xD;
          -  Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma.&#xD;
             Features of neuroendocrine phenotype are allowed.&#xD;
&#xD;
          -  Patients must have evidence of castration resistant metastatic disease and eligible&#xD;
             for Enzalutamide per standard guidelines. Castration resistant non-metastatic disease&#xD;
             is allowed in phase I study if subject is candidate for Enzalutamide.&#xD;
&#xD;
          -  Patients must have and ECOG performance status of ≤ 2.(appendix D)&#xD;
&#xD;
          -  Patients must be on continuous LHRH agonist or antagonist treatment or surgically&#xD;
             castrated with castrate levels of testosterone (&lt; 20 ng/dl).&#xD;
&#xD;
          -  Any number of prior chemotherapy regimens are allowed. Chemotherapy naïve patients are&#xD;
             allowed.&#xD;
&#xD;
          -  If patient is already on Enzalutamide at a dose of 160mg daily, he is allowed if he&#xD;
             can have baseline image and PSA within 1 month of the start of entinostat.&#xD;
&#xD;
          -  Patients may have had androgen synthesis inhibitors or other investigational drugs.&#xD;
             Patient must have discontinued flutamide or nilutamide or other AR targeted agents&#xD;
             (including abiraterone) for at least 4 weeks and bicalutamide for at least 6 weeks&#xD;
             prior to day 1 of treatment.&#xD;
&#xD;
          -  Patients receiving treatment with bisphosphonates or denosumab must remain on&#xD;
             treatment during the study.&#xD;
&#xD;
          -  Patients must not require concurrent radiation or other chemotherapy while receiving&#xD;
             protocol therapy. Patients may have received previous radiation but must have&#xD;
             completed radiation at least 4 weeks (8 weeks for radiation to the brain) prior to&#xD;
             registration.&#xD;
&#xD;
          -  Patients must have recovered to grade ≤ 1 from all acute toxicity of previous&#xD;
             radiation, hormonal or chemotherapy treatments.&#xD;
&#xD;
          -  Patient agrees to use an acceptable method for contraception during the entire study&#xD;
             treatment period through 4 months after the last dose of entinostat.&#xD;
&#xD;
          -  Adequate renal function as defined by serum creatinine ≤ 1.5 x ULN. If creatinine &gt;1.5&#xD;
             x ULN, calculated or measured creatinine clearance must be ≥ 60 mL/minute&#xD;
             (Cockcroft-Gault).&#xD;
&#xD;
          -  ANC &gt; 1500/mm³, platelets &gt; 100,000/mm³, Hgb &gt; 9 g/dL.&#xD;
&#xD;
          -  Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)&lt; 1.5 x ULN. AST and/or ALT may be up&#xD;
             to 5X ULN in the setting of known liver metastasis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients meeting any of the following exclusion criteria are not to be enrolled in the&#xD;
        study:&#xD;
&#xD;
          -  Patient was treated and discontinued Enzalutamide previously for any reason.&#xD;
&#xD;
          -  Major surgery within 28 days or serious infection requiring IV antibiotics within 14&#xD;
             days preceding the first dose of study treatment&#xD;
&#xD;
          -  Patient has received other investigational drugs within 14 days before enrollment.&#xD;
&#xD;
          -  Known GI disease or GI procedure that could impact drug absorption in the upper bowel,&#xD;
             or tolerance of Entinostat. Examples include but are not limited to partial&#xD;
             gastrectomy, small bowel resection, pancreatectomy, malabsorption or celiac disease&#xD;
&#xD;
          -  Ongoing nausea or vomiting of any severity without improvement after appropriate&#xD;
             treatment.&#xD;
&#xD;
          -  &gt; Grade 1 diarrhea, not controlled with appropriate treatment.&#xD;
&#xD;
          -  History of uncontrolled sleep apnea syndrome and other conditions that could result in&#xD;
             excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease&#xD;
             requiring supplemental oxygen.&#xD;
&#xD;
          -  Clinical and/or radiographic evidence of cerebral metastases. However, patients who&#xD;
             have a history of central nervous system (CNS) metastasis but who have no radiographic&#xD;
             or clinical evidence of residual tumor (eg, following complete surgical resection or&#xD;
             stereotactic radiosurgery) are not excluded from participation in this study.&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe&#xD;
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute&#xD;
             ischemia or active conduction system abnormalities. Prior to study entry, any EKG&#xD;
             abnormality at Screening has to be documented by the investigator as not medically&#xD;
             relevant.&#xD;
&#xD;
          -  Serious medical or psychiatric illness or laboratory abnormality that may increase the&#xD;
             risk associated with study participation or investigational product administration or&#xD;
             may interfere with the interpretation of study results and, in the judgment of the&#xD;
             investigator, would make the patient inappropriate for enrollment in this study.&#xD;
&#xD;
          -  Any other currently active malignancy (excluding controlled non-melanoma skin cancer).&#xD;
             Patients are considered NOT to have &quot;currently active&quot; malignancy if they have&#xD;
             completed any necessary therapy and are considered by their physician to be at less&#xD;
             than 30% risk of relapse.&#xD;
&#xD;
          -  Treatment with clinically significant enzyme inducers, such as the enzyme-inducing&#xD;
             antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin,&#xD;
             rifapentine or St. John's Wort within 14 days prior to the first dose of Entinostat&#xD;
             and during the study.&#xD;
&#xD;
          -  History of seizure and on active therapy for seizure&#xD;
&#xD;
          -  Known history of uncontrolled human immunodeficiency virus (HIV) infection. HIV&#xD;
             positive patients will be allowed if they are on treatment and have an adequate CD4&#xD;
             count (CD4 count &gt;200). Screening is not required in the absence of clinical findings&#xD;
             or suspicion.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianquig Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>George Washington Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>George Washington University - Medical Faculty Associates</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.gov/</url>
    <description>NCT00859472</description>
  </link>
  <link>
    <url>https://clinicaltrials.gov/</url>
    <description>NCT00878436</description>
  </link>
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  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 26, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>George Washington University</investigator_affiliation>
    <investigator_full_name>Jianqing Lin</investigator_full_name>
    <investigator_title>Medical Oncologist</investigator_title>
  </responsible_party>
  <keyword>Castration resistant prostate cancer</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>Entinostat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03829930
org study id: GWCC 1000
nct id: NCT03829930
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To determine the safety and tolerability of Entinostat in combination with Enzalutamide in
      metastatic castrate resistant prostate cancer
This study is designed to determine the safety and tolerability of Entinostat with
      Enzalutamide for treatment of patients with castration-resistant prostate cancer. There will
      be two dose levels of Entinostat in combination with same dose of Enzalutamide. Patients will
      be followed during treatment and 1 month post discontinuation.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: 3+3 Design
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of a suitable dose of Entinostat in combination with Enzalutamide
time frame: 18 months
description: Number of participants who experience an adverse event assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
measure: Progression Free Survival
time frame: 3 years
description: Number of participants who survive without disease progression
measure: Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs
time frame: 18 months
description: Analysis of immunomodulatory effects of Entinostat
arm group label: Entinostat and Enzalutamide
arm group type: Experimental
description: Entinostat and Enzalutamide
intervention type: Drug
intervention name: Entinostat
description: Entinostat is formulated for oral administration. A food effect is evident for entinostat; exposure is significantly reduced when entinostat is administered with a high fat meal. Accordingly, entinostat is to be administered on an empty stomach, at least 1 hour before and 2 hours after a meal. Entinostat tablets should not be split, crushed, or chewed. Consult the individual clinical protocols for specific dosing instructions.
Dose level 1: 3mg PO weekly. Dose level 2: 5mg PO weekly.
arm group label: Entinostat and Enzalutamide
other name: SYND-275 amd MS-275
intervention type: Drug
intervention name: Enzalutamide
description: Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.
arm group label: Entinostat and Enzalutamide
other name: MDV3100
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jianquig Lin, MD
role: Principal Investigator
affiliation: George Washington Cancer Center
facility: 
country: United States
url: https://clinicaltrials.gov/
description: NCT00859472
url: https://clinicaltrials.gov/
description: NCT00878436
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responsible party type: Principal Investigator
investigator affiliation: George Washington University
investigator full name: Jianqing Lin
investigator title: Medical Oncologist
mesh term: Prostatic Neoplasms
mesh term: Entinostat
sharing ipd: Undecided