<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/NCT03279250</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0527</org_study_id>
    <secondary_id>NCI-2018-01064</secondary_id>
    <secondary_id>2016-0527</secondary_id>
    <nct_id>NCT03279250</nct_id>
  </id_info>
  <brief_title>Apalutamide and Gonadotropin-Releasing Hormone Analog With or Without Abiraterone Acetate in Treating Participants With Prostate Cancer</brief_title>
  <official_title>A Pre-Operative Study to Assess the Effects of Apalutamide Plus LHRH Agonist or Apalutamide Plus Abiraterone Acetate Plus LHRH Agonist for Six Months for Prostate Cancer Patients at High Risk for Recurrence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well apalutamide and gonadotropin-releasing hormone analog&#xD;
      with or without abiraterone acetate work in treating participants with prostate cancer prior&#xD;
      to surgery. Apalutamide and abiraterone acetate may stop the growth of cancer cells either by&#xD;
      killing the cells or by blocking some of the enzymes needed for cell growth. Hormone therapy,&#xD;
      using gonadotropin-releasing hormone analog, may fight prostate cancer by lowering the amount&#xD;
      of testosterone the body makes. Giving apalutamide, gonadotropin-releasing hormone analog,&#xD;
      and abiraterone acetate may work better in treating participants with prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the rate of pathologic stage =&lt; pT2N0 at prostatectomy for Group A&#xD;
      (gonadotropin-releasing hormone analog [luteinizing hormone releasing hormone agonist&#xD;
      (LHRHa)] plus apalutamide 240 mg orally [PO] daily for 6 months as preoperative therapy) and&#xD;
      Group B (LHRHa plus apalutamide 240 mg PO daily plus abiraterone acetate 1000 mg PO daily and&#xD;
      prednisone 5 mg PO once daily [QD] for 6 months as preoperative therapy).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the tumor epithelium volume following treatment in groups A and B. II. To assess&#xD;
      the rate of positive surgical margins in Group A and Group B. III. To assess the time to&#xD;
      prostate specific antigen (PSA) recurrence (TTRPSA). IV. To assess the safety profile of the&#xD;
      two treatment arms (apalutamide with and without abiraterone acetate and low dose prednisone)&#xD;
      for six months in a preoperative setting.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Assessment of the steroid hormone metabolome in blood plasma and tissue by liquid&#xD;
      chromatography tandem mass spectrometry.&#xD;
&#xD;
      II. Assessment of androgen signaling (canonical and non-canonical) and candidate pathways of&#xD;
      resistance to androgen signaling inhibition by protein and ribonucleic acid (RNA) analysis.&#xD;
&#xD;
      III. Assessment of citrate intracellular tricarboxylic acid cycle (TCA) metabolite&#xD;
      concentrations with liquid chromatography-tandem mass spectrometry (LCMS/MS).&#xD;
&#xD;
      IV. Proportion of patients who achieve pathological complete response (CR). V. Hyperpolarized&#xD;
      1-13C-pyruvate imaging at study entry and at 3 months in Arm A and Arm B.&#xD;
&#xD;
      OUTLINE: Participants are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM A: Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or&#xD;
      triptorelin as determined by treating physician) intramuscularly (IM) once every 3 months and&#xD;
      apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of&#xD;
      disease progression or unacceptable toxicity. Beginning no less than 48 hours after&#xD;
      completion of therapy, participants undergo radical prostatectomy.&#xD;
&#xD;
      ARM B: Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm&#xD;
      A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to&#xD;
      6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less&#xD;
      than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
&#xD;
      After completion of study treatment, participants are followed for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Actual">May 11, 2021</completion_date>
  <primary_completion_date type="Actual">May 11, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Number of Participants With Rate of Pathologic Stage =&lt; pT2N0 at Prostatectomy</measure>
    <time_frame>At the time of radical prostatectomy</time_frame>
    <description>The study will provide a point estimate and 95% confidence interval of the proportion of patients with pathologic stage =&lt; pT2N0 at prostatectomy for each arm. Patient characteristics will be summarized using descriptive statistics for each arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Incidence of Adverse Events</measure>
    <time_frame>From screening up to 4 weeks post-surgery, an average of 7 months</time_frame>
    <description>Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Incidence of serious adverse events and 95% confidence interval will be provided overall as well as for each major affected organ category.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Epithelium Volume in the Surgical Specimen</measure>
    <time_frame>At the time of radical prostatectomy</time_frame>
    <description>Tumor volume will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Positive Surgical Margins in the Surgical Specimen</measure>
    <time_frame>At the time of radical prostatectomy</time_frame>
    <description>Presence of positive surgical margins will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Prostate Specific Antigen Recurrence (TTRPSA)</measure>
    <time_frame>From the date of randomization up to 4 weeks post-surgery</time_frame>
    <description>TTRPSA will be summarized by Kaplan-Meier estimates and confidence intervals. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of Steroid Hormone Metabolome in Blood Plasma and Tissue</measure>
    <time_frame>At radical prostatectomy</time_frame>
    <description>Steroid hormone metabolome in blood plasma and tissue will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of Protein and Ribonucleic Acid (RNA) Analysis Results</measure>
    <time_frame>At radical prostatectomy</time_frame>
    <description>Assessment of protein and RNA analysis results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Citrate Intracellular Tricarboxylic Acid (TCA) Cycle Metabolite Concentrations</measure>
    <time_frame>At radical prostatectomy</time_frame>
    <description>Citrate intracellular TCA cycle metabolite concentrations will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pathological Response</measure>
    <time_frame>Up to 4 weeks post-surgery</time_frame>
    <description>Pathological response will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hyperpolarized 1-13C-pyruvate Imaging Results</measure>
    <time_frame>Up to 4 weeks post-surgery</time_frame>
    <description>Hyperpolarized 1-13C-pyruvate imaging results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Prostate Adenocarcinoma</condition>
  <condition>Stage IIB Prostate Cancer AJCC v8</condition>
  <condition>Stage IIC Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIA Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIC Prostate Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Arm A (LHRHa, apalutamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abiraterone Acetate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <other_name>CB7630</other_name>
    <other_name>Yonsa</other_name>
    <other_name>Zytiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apalutamide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (LHRHa, apalutamide)</arm_group_label>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <other_name>ARN 509</other_name>
    <other_name>ARN-509</other_name>
    <other_name>ARN509</other_name>
    <other_name>Erleada</other_name>
    <other_name>JNJ 56021927</other_name>
    <other_name>JNJ-56021927</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Gonadotropin-releasing Hormone Analog</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Arm A (LHRHa, apalutamide)</arm_group_label>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <other_name>GnRH Agonist</other_name>
    <other_name>GnRH Analog</other_name>
    <other_name>Gonadotropin-Releasing Hormone Agonist</other_name>
    <other_name>Gonadotropin-Releasing Hormone Analogue</other_name>
    <other_name>LH-RH agonist</other_name>
    <other_name>LH-RH Analogs</other_name>
    <other_name>LHRH Agonist</other_name>
    <other_name>luteinizing hormone-releasing hormone agonist</other_name>
    <other_name>Luteinizing Hormone-Releasing Hormone Analog</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <other_name>.delta.1-Cortisone</other_name>
    <other_name>1, 2-Dehydrocortisone</other_name>
    <other_name>Adasone</other_name>
    <other_name>Cortancyl</other_name>
    <other_name>Dacortin</other_name>
    <other_name>DeCortin</other_name>
    <other_name>Decortisyl</other_name>
    <other_name>Decorton</other_name>
    <other_name>Delta 1-Cortisone</other_name>
    <other_name>Delta-Dome</other_name>
    <other_name>Deltacortene</other_name>
    <other_name>Deltacortisone</other_name>
    <other_name>Deltadehydrocortisone</other_name>
    <other_name>Deltasone</other_name>
    <other_name>Deltison</other_name>
    <other_name>Deltra</other_name>
    <other_name>Econosone</other_name>
    <other_name>Lisacort</other_name>
    <other_name>Meprosona-F</other_name>
    <other_name>Metacortandracin</other_name>
    <other_name>Meticorten</other_name>
    <other_name>Ofisolona</other_name>
    <other_name>Orasone</other_name>
    <other_name>Panafcort</other_name>
    <other_name>Panasol-S</other_name>
    <other_name>Paracort</other_name>
    <other_name>Perrigo Prednisone</other_name>
    <other_name>PRED</other_name>
    <other_name>Predicor</other_name>
    <other_name>Predicorten</other_name>
    <other_name>Prednicen-M</other_name>
    <other_name>Prednicort</other_name>
    <other_name>Prednidib</other_name>
    <other_name>Prednilonga</other_name>
    <other_name>Predniment</other_name>
    <other_name>Prednisone Intensol</other_name>
    <other_name>Prednisonum</other_name>
    <other_name>Prednitone</other_name>
    <other_name>Promifen</other_name>
    <other_name>Rayos</other_name>
    <other_name>Servisone</other_name>
    <other_name>SK-Prednisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical Prostatectomy</intervention_name>
    <description>Undergo radical prostatectomy</description>
    <arm_group_label>Arm A (LHRHa, apalutamide)</arm_group_label>
    <arm_group_label>Arm B (LHRHa, apalutamide, abiraterone acetate)</arm_group_label>
    <other_name>Prostatovesiculectomy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed adenocarcinoma of the&#xD;
             prostate with no histological variants (such as small cell, sarcomatoid, pure ductal&#xD;
             cancer, transitional cell carcinoma).&#xD;
&#xD;
          -  Patients may have received one prior depot injection of LHRH agonist or LHRH&#xD;
             antagonist (degarelix) within 30 days prior to study entry. Patients who have received&#xD;
             any other prior hormonal therapy or any chemotherapy for prostate cancer will be&#xD;
             excluded. (Patients who have discontinued finasteride or dutasteride or testosterone&#xD;
             supplement for at least 2 weeks will be allowed to enroll).&#xD;
&#xD;
          -  Be willing/able to adhere to the prohibitions and restrictions specified in this&#xD;
             protocol.&#xD;
&#xD;
          -  Have signed an informed consent document indicating that the subject understands the&#xD;
             purpose of and procedures required for the study and is willing to participate in the&#xD;
             study.&#xD;
&#xD;
          -  Written authorization for use and release of health and research study information has&#xD;
             been obtained.&#xD;
&#xD;
          -  Pathology review at Monroe Dunaway (MD) Anderson (Note: if patient's prostate biopsy&#xD;
             was not read at MD Anderson, it must be reviewed at the study site to confirm&#xD;
             eligibility).&#xD;
&#xD;
          -  Prostate biopsy. If previous biopsy has been performed within 3 months of screening,&#xD;
             second biopsy procedure will not be required, if archival biopsies and at least one&#xD;
             formalin fixed paraffin embedded biopsy tissue block containing tumor is available.&#xD;
&#xD;
          -  The following tumor stage and Gleason scores: a) clinical &gt;= stage T1c/T2 tumor with&#xD;
             Gleason score &gt;=8 b) clinical stage &gt;= T2b tumor with Gleason score &gt;= 7 and PSA &gt; 10&#xD;
             ng/ml.&#xD;
&#xD;
          -  Serum testosterone &gt; 150 ng/dL. For patients treated up to 1 month of LHRH agonist, a&#xD;
             testosterone measurement prior to the LHRH treatment will be used to determine&#xD;
             eligibility, and must have been &gt; 150 ng/dL. If no testosterone level is available&#xD;
             from before LHRHa injection up to 30 days prior to study entry, the patient will be&#xD;
             ineligible.&#xD;
&#xD;
          -  Patient is suitable for prostatectomy.&#xD;
&#xD;
          -  No evidence of metastatic disease as determined by imaging procedures.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL independent of transfusion.&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/uL.&#xD;
&#xD;
          -  Absolute peripheral neutrophil count (ANC) &gt; 1,000.&#xD;
&#xD;
          -  Creatinine clearance &gt;= 50 mL/min.&#xD;
&#xD;
          -  Serum potassium &gt;= 3.5 mmol/L.&#xD;
&#xD;
          -  Serum bilirubin =&lt; 1.5 x upper limit of normal (ULN).&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN.&#xD;
&#xD;
          -  Serum albumin &gt;= 3 g/dl.&#xD;
&#xD;
          -  Able to swallow the study drug whole as a tablet.&#xD;
&#xD;
          -  Patients must have normal coagulation profile and no history of substantial&#xD;
             non-iatrogenic bleeding diathesis.&#xD;
&#xD;
          -  Agrees to use a condom (even men with vasectomies) and another effective method of&#xD;
             birth control if he is having sex with a woman of childbearing potential or agrees to&#xD;
             use a condom if he is having sex with a woman who is pregnant while on study drug and&#xD;
             for 3 months following the last dose of study drug. Must also agree not to donate&#xD;
             sperm during the study and for 3 months after receiving the last dose of study drug.&#xD;
&#xD;
          -  Willing to take abiraterone acetate on an empty stomach; no food should be consumed at&#xD;
             least two hours before and for at least one hour after the dose of abiraterone acetate&#xD;
             is taken.&#xD;
&#xD;
          -  Life expectancy of greater than 12 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had any prior chemotherapy or radiotherapy for prostate cancer.&#xD;
&#xD;
          -  Patients who have had &gt; 1 LHRH agonist or antagonist depot injection or received depot&#xD;
             injection &gt; 30 days before study entry.&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents.&#xD;
&#xD;
          -  Patients may not be receiving the concomitant administration of any systemic therapy,&#xD;
             biologic therapy, or other agents with anti-tumor activity against prostate cancer&#xD;
             while the patients are on study.&#xD;
&#xD;
          -  Patients with known metastatic prostate cancer.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to leuprolide acetate, abiraterone acetate, prednisone or apalutamide or&#xD;
             other agents used in the study.&#xD;
&#xD;
          -  Uncontrolled intercurrent 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.&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral&#xD;
             therapy are ineligible because of the potential for pharmacokinetic interactions with&#xD;
             apalutamide and abiraterone. Appropriate studies will be undertaken in patients&#xD;
             receiving combination antiretroviral therapy when indicated.&#xD;
&#xD;
          -  Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a&#xD;
             strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing&#xD;
             frequency.&#xD;
&#xD;
          -  Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a&#xD;
             narrow therapeutic index. If an alternative treatment cannot be used, exercise caution&#xD;
             and consider a dose reduction of the concomitant CYP2D6 substrate.&#xD;
&#xD;
          -  Patients receiving medications known to lower the seizure threshold are ineligible&#xD;
             unless discontinued or substituted at least 4 weeks prior to study entry. These&#xD;
             include: 1) aminophylline/theophylline; 2) atypical antipsychotics (e.g., clozapine,&#xD;
             olanzapine, risperidone, ziprasidone); 3) bupropion; 4) lithium; 5) pethidine; 6)&#xD;
             phenothiazine antipsychotics (e.g., prochlorperazine (compazine), chlorpromazine,&#xD;
             mesoridazine, thioridazine); 7) tricyclic and tetracyclic antidepressants (e.g.,&#xD;
             amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).&#xD;
&#xD;
          -  Chronically uncontrolled hypertension, defined conventionally as consistent systolic&#xD;
             pressures above 170 or diastolic pressures above 110 despite anti-hypertensive&#xD;
             therapy. Note that this is NOT a criterion related to particular blood pressure (BP)&#xD;
             results at the time of assessment for eligibility, nor does it apply to acute BP&#xD;
             excursions that are related to iatrogenic causes, acute pain or other transient,&#xD;
             reversible causes. (for example doctor's visit related stress i.e. &quot;white coat&#xD;
             syndrome&quot;.&#xD;
&#xD;
          -  Requirement for corticosteroids greater than the equivalent of 10 mg of prednisone&#xD;
             daily for more than 2 weeks.&#xD;
&#xD;
          -  Poorly controlled diabetes defined by hemoglobin A1C &gt; 9.0 at screening.&#xD;
&#xD;
          -  Active or symptomatic viral hepatitis or chronic liver disease.&#xD;
&#xD;
          -  Known history of pituitary or adrenal dysfunction.&#xD;
&#xD;
          -  Other malignancy, except non-melanoma skin cancer, that is active or has a &gt;= 30%&#xD;
             probability of recurrence within 12 months.&#xD;
&#xD;
          -  History of gastrointestinal disorders (medical disorders or extensive surgery) which&#xD;
             may interfere with the absorption of the study drug.&#xD;
&#xD;
          -  Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens,&#xD;
             ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or LHRH&#xD;
             agonists/antagonists (Note: LHRH allowed if begun within 1 month of day 1).&#xD;
&#xD;
          -  Prior systemic treatment with an azole drug within four weeks of cycle 1 day 1.&#xD;
&#xD;
          -  Current enrollment in an investigational drug or device study or participation in such&#xD;
             a study within 30 days of cycle 1 day 1.&#xD;
&#xD;
          -  Allergies, hypersensitivity, or intolerance to prednisone, LHRH analog or excipients&#xD;
             of prednisone LHRH analog, abiraterone acetate and apalutamide.&#xD;
&#xD;
          -  Previous use of abiraterone acetate or other investigational CYP17 inhibitor (e.g.,&#xD;
             TAK-700).&#xD;
&#xD;
          -  Previous investigational antiandrogens (e.g., apalutamide, enzalutamide, BMS-641988).&#xD;
&#xD;
          -  Condition or situation which, in the investigator's opinion, may put the patient at&#xD;
             significant risk, may confound the study results, or may interfere significantly with&#xD;
             patient's participation in the study.&#xD;
&#xD;
          -  Patients unable to tolerate transrectal ultrasound.&#xD;
&#xD;
          -  Anti-androgens (steroidal or non-steroidal) such as cyproterone acetate, flutamide,&#xD;
             nilutamide, bicalutamide, etc. other than assigned study drug unless given for =&lt; 4&#xD;
             weeks.&#xD;
&#xD;
          -  Estrogens, progestational agents such as megestrol, medroxyprogesterone,&#xD;
             diethylstilbestrol (DES), cyproterone, spironolactone &gt; 50 mg/kg, etc. unless&#xD;
             discontinued at least two weeks prior to randomization.&#xD;
&#xD;
          -  Androgens such as testosterone, dehydroepiandrosterone (DHEA), etc. unless&#xD;
             discontinued at least two weeks prior to randomization.&#xD;
&#xD;
          -  Herbal products that may decrease PSA levels (e.g., saw palmetto) unless discontinued&#xD;
             two weeks prior to randomization.&#xD;
&#xD;
          -  Active infection or other medical condition that would make prednisone/prednisolone&#xD;
             (corticosteroid) use contraindicated.&#xD;
&#xD;
          -  Severe hepatic impairment (Child-Pugh Class C).&#xD;
&#xD;
          -  History of significant bleeding disorder unrelated to cancer, including: 1) diagnosed&#xD;
             congenital bleeding disorders (e.g., von Willebrand's disease); 2) diagnosed acquired&#xD;
             bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of&#xD;
             screening visit; 3) history of gastrointestinal (GI) bleeding within 3 months of&#xD;
             screening visit requiring &gt;= 2 units packed red blood cells.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease including: 1) myocardial infarction&#xD;
             within 6 months of screening visit; 2) uncontrolled angina within 3 months of&#xD;
             screening visit; 3) congestive heart failure New York Heart Association (NYHA) class 3&#xD;
             or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the&#xD;
             past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless&#xD;
             a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within&#xD;
             three months of the Screening visit results in a left ventricular ejection fraction&#xD;
             that is &gt;= 50%. 4) history of clinically significant ventricular arrhythmias (e.g.,&#xD;
             ventricular tachycardia, ventricular fibrillation, torsade de pointes). 5) prolonged&#xD;
             corrected QT interval by the Fridericia correction formula (QTcF) on the screening&#xD;
             electrocardiogram (ECG) &gt; 470 msec. 6) history of Mobitz II second degree or third&#xD;
             degree heart block without a permanent pacemaker in place. 7) hypotension (systolic&#xD;
             blood pressure &lt; 86 mmHg or bradycardia with a heart rate of &lt; 50 beats per minute on&#xD;
             the screening ECG, unless pharmaceutically induced and thus reversible (i.e. beta&#xD;
             blockers).&#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>Christopher Logothetis</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <results_first_submitted>May 11, 2022</results_first_submitted>
  <results_first_submitted_qc>July 14, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 10, 2022</results_first_posted>
  <last_update_submitted>July 14, 2022</last_update_submitted>
  <last_update_submitted_qc>July 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</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>Prednisone</mesh_term>
    <mesh_term>Cortisone</mesh_term>
    <mesh_term>Abiraterone Acetate</mesh_term>
    <mesh_term>Hormones</mesh_term>
    <mesh_term>Prolactin Release-Inhibiting Factors</mesh_term>
  </intervention_browse>
  <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>January 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03279250/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>86 participants signed consent, 18 participants were not randomized (10 screen failures, 3 Insurance complications, 5 consent withdrawn )</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm A (LHRHa, Apalutamide)</title>
          <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
        <group group_id="P2">
          <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
          <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Abiraterone Acetate: Given PO&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Prednisone: Given PO&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A (LHRHa, Apalutamide)</title>
          <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
        <group group_id="B2">
          <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
          <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Abiraterone Acetate: Given PO&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Prednisone: Given PO&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="34"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="68"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="34"/>
                    <count group_id="B2" value="34"/>
                    <count group_id="B3" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" lower_limit="54" upper_limit="75"/>
                    <measurement group_id="B2" value="62" lower_limit="43" upper_limit="77"/>
                    <measurement group_id="B3" value="63" lower_limit="43" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="34"/>
                    <count group_id="B2" value="34"/>
                    <count group_id="B3" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="34"/>
                    <count group_id="B2" value="34"/>
                    <count group_id="B3" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Number of Participants With Rate of Pathologic Stage =&lt; pT2N0 at Prostatectomy</title>
        <description>The study will provide a point estimate and 95% confidence interval of the proportion of patients with pathologic stage =&lt; pT2N0 at prostatectomy for each arm. Patient characteristics will be summarized using descriptive statistics for each arm.</description>
        <time_frame>At the time of radical prostatectomy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A (LHRHa, Apalutamide)</title>
            <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
          <group group_id="O2">
            <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
            <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Participants With Rate of Pathologic Stage =&lt; pT2N0 at Prostatectomy</title>
          <description>The study will provide a point estimate and 95% confidence interval of the proportion of patients with pathologic stage =&lt; pT2N0 at prostatectomy for each arm. Patient characteristics will be summarized using descriptive statistics for each arm.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Incidence of Adverse Events</title>
        <description>Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Incidence of serious adverse events and 95% confidence interval will be provided overall as well as for each major affected organ category.</description>
        <time_frame>From screening up to 4 weeks post-surgery, an average of 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A (LHRHa, Apalutamide)</title>
            <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
          <group group_id="O2">
            <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
            <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Incidence of Adverse Events</title>
          <description>Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Incidence of serious adverse events and 95% confidence interval will be provided overall as well as for each major affected organ category.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Serious</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non Serious</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Epithelium Volume in the Surgical Specimen</title>
        <description>Tumor volume will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>At the time of radical prostatectomy</time_frame>
        <population>Tumor epithelium volume in the surgical specimen analysis is unavailable due to no data collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A (LHRHa, Apalutamide)</title>
            <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
          <group group_id="O2">
            <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
            <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Epithelium Volume in the Surgical Specimen</title>
          <description>Tumor volume will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
          <population>Tumor epithelium volume in the surgical specimen analysis is unavailable due to no data collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Positive Surgical Margins in the Surgical Specimen</title>
        <description>Presence of positive surgical margins will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>At the time of radical prostatectomy</time_frame>
        <population>Assessment of positive surgical margins in the surgical specimen analysis is not available due to no data collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A (LHRHa, Apalutamide)</title>
            <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
          <group group_id="O2">
            <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
            <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Positive Surgical Margins in the Surgical Specimen</title>
          <description>Presence of positive surgical margins will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
          <population>Assessment of positive surgical margins in the surgical specimen analysis is not available due to no data collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Prostate Specific Antigen Recurrence (TTRPSA)</title>
        <description>TTRPSA will be summarized by Kaplan-Meier estimates and confidence intervals. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>From the date of randomization up to 4 weeks post-surgery</time_frame>
        <population>Time to prostate specific antigen recurrence (TTRPSA) analysis is not available due to no data collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A (LHRHa, Apalutamide)</title>
            <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
          <group group_id="O2">
            <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
            <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Prostate Specific Antigen Recurrence (TTRPSA)</title>
          <description>TTRPSA will be summarized by Kaplan-Meier estimates and confidence intervals. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
          <population>Time to prostate specific antigen recurrence (TTRPSA) analysis is not available due to no data collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Assessment of Steroid Hormone Metabolome in Blood Plasma and Tissue</title>
        <description>Steroid hormone metabolome in blood plasma and tissue will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>At radical prostatectomy</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Assessment of Protein and Ribonucleic Acid (RNA) Analysis Results</title>
        <description>Assessment of protein and RNA analysis results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>At radical prostatectomy</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Citrate Intracellular Tricarboxylic Acid (TCA) Cycle Metabolite Concentrations</title>
        <description>Citrate intracellular TCA cycle metabolite concentrations will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>At radical prostatectomy</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pathological Response</title>
        <description>Pathological response will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>Up to 4 weeks post-surgery</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hyperpolarized 1-13C-pyruvate Imaging Results</title>
        <description>Hyperpolarized 1-13C-pyruvate imaging results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.</description>
        <time_frame>Up to 4 weeks post-surgery</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening up to 4 weeks post-surgery, an average of 7 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A (LHRHa, Apalutamide)</title>
          <description>Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
        <group group_id="E2">
          <title>Arm B (LHRHa, Apalutamide, Abiraterone Acetate)</title>
          <description>Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.&#xD;
Abiraterone Acetate: Given PO&#xD;
Apalutamide: Given PO&#xD;
Gonadotropin-releasing Hormone Analog: Given IM&#xD;
Prednisone: Given PO&#xD;
Radical Prostatectomy: Undergo radical prostatectomy</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.03)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.03)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="28" subjects_affected="21" subjects_at_risk="34"/>
                <counts group_id="E2" events="19" subjects_affected="15" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>HbA1c increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>TSH increased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hypothyrodism</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>GERD</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="36" subjects_affected="30" subjects_at_risk="34"/>
                <counts group_id="E2" events="27" subjects_affected="24" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALT increase</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="14" subjects_affected="8" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>AST increase</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="14" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Lipase increase</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="17" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decrease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Amylase increase</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="13" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>White blood cell decrease</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="16" subjects_at_risk="34"/>
                <counts group_id="E2" events="15" subjects_affected="13" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>ACTH increase</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Insulin increase</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>LDH increase</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Vitamin D decrease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="34"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Personality change</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="34"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="40" subjects_affected="31" subjects_at_risk="34"/>
                <counts group_id="E2" events="31" subjects_affected="25" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="14" subjects_affected="9" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Christopher Logothetis, MD-Professor, Genitourinary Medical Oncology</name_or_title>
      <organization>UT MD Anderson Cancer Center</organization>
      <phone>(713) 563-7210</phone>
      <email>clogothe@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03279250
org study id: 2016-0527
secondary id: NCI-2018-01064
secondary id: 2016-0527
nct id: NCT03279250
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well apalutamide and gonadotropin-releasing hormone analog
      with or without abiraterone acetate work in treating participants with prostate cancer prior
      to surgery. Apalutamide and abiraterone acetate may stop the growth of cancer cells either by
      killing the cells or by blocking some of the enzymes needed for cell growth. Hormone therapy,
      using gonadotropin-releasing hormone analog, may fight prostate cancer by lowering the amount
      of testosterone the body makes. Giving apalutamide, gonadotropin-releasing hormone analog,
      and abiraterone acetate may work better in treating participants with prostate cancer.
PRIMARY OBJECTIVES:

      I. To assess the rate of pathologic stage =< pT2N0 at prostatectomy for Group A
      (gonadotropin-releasing hormone analog [luteinizing hormone releasing hormone agonist
      (LHRHa)] plus apalutamide 240 mg orally [PO] daily for 6 months as preoperative therapy) and
      Group B (LHRHa plus apalutamide 240 mg PO daily plus abiraterone acetate 1000 mg PO daily and
      prednisone 5 mg PO once daily [QD] for 6 months as preoperative therapy).

      SECONDARY OBJECTIVES:

      I. To assess the tumor epithelium volume following treatment in groups A and B. II. To assess
      the rate of positive surgical margins in Group A and Group B. III. To assess the time to
      prostate specific antigen (PSA) recurrence (TTRPSA). IV. To assess the safety profile of the
      two treatment arms (apalutamide with and without abiraterone acetate and low dose prednisone)
      for six months in a preoperative setting.

      EXPLORATORY OBJECTIVES:

      I. Assessment of the steroid hormone metabolome in blood plasma and tissue by liquid
      chromatography tandem mass spectrometry.

      II. Assessment of androgen signaling (canonical and non-canonical) and candidate pathways of
      resistance to androgen signaling inhibition by protein and ribonucleic acid (RNA) analysis.

      III. Assessment of citrate intracellular tricarboxylic acid cycle (TCA) metabolite
      concentrations with liquid chromatography-tandem mass spectrometry (LCMS/MS).

      IV. Proportion of patients who achieve pathological complete response (CR). V. Hyperpolarized
      1-13C-pyruvate imaging at study entry and at 3 months in Arm A and Arm B.

      OUTLINE: Participants are randomized to 1 of 2 arms.

      ARM A: Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or
      triptorelin as determined by treating physician) intramuscularly (IM) once every 3 months and
      apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of
      disease progression or unacceptable toxicity. Beginning no less than 48 hours after
      completion of therapy, participants undergo radical prostatectomy.

      ARM B: Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm
      A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to
      6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less
      than 48 hours after completion of therapy, participants undergo radical prostatectomy.

      After completion of study treatment, participants are followed for 4 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Number of Participants With Rate of Pathologic Stage =< pT2N0 at Prostatectomy
time frame: At the time of radical prostatectomy
description: The study will provide a point estimate and 95% confidence interval of the proportion of patients with pathologic stage =< pT2N0 at prostatectomy for each arm. Patient characteristics will be summarized using descriptive statistics for each arm.
measure: Number of Participants With Incidence of Adverse Events
time frame: From screening up to 4 weeks post-surgery, an average of 7 months
description: Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Incidence of serious adverse events and 95% confidence interval will be provided overall as well as for each major affected organ category.
measure: Tumor Epithelium Volume in the Surgical Specimen
time frame: At the time of radical prostatectomy
description: Tumor volume will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Assessment of Positive Surgical Margins in the Surgical Specimen
time frame: At the time of radical prostatectomy
description: Presence of positive surgical margins will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Time to Prostate Specific Antigen Recurrence (TTRPSA)
time frame: From the date of randomization up to 4 weeks post-surgery
description: TTRPSA will be summarized by Kaplan-Meier estimates and confidence intervals. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Secondary categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Assessment of Steroid Hormone Metabolome in Blood Plasma and Tissue
time frame: At radical prostatectomy
description: Steroid hormone metabolome in blood plasma and tissue will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Assessment of Protein and Ribonucleic Acid (RNA) Analysis Results
time frame: At radical prostatectomy
description: Assessment of protein and RNA analysis results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Citrate Intracellular Tricarboxylic Acid (TCA) Cycle Metabolite Concentrations
time frame: At radical prostatectomy
description: Citrate intracellular TCA cycle metabolite concentrations will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Pathological Response
time frame: Up to 4 weeks post-surgery
description: Pathological response will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
measure: Hyperpolarized 1-13C-pyruvate Imaging Results
time frame: Up to 4 weeks post-surgery
description: Hyperpolarized 1-13C-pyruvate imaging results will be summarized descriptively and graphically. Comparisons between two the arms or patient subgroups will use a t-test or non-parametric alternative as indicated. Exploratory categorical endpoints will be summarized using proportions with 95% confidence intervals. Comparisons between the two arms will use a chi-square test or Fisher's exact if indicated.
arm group label: Arm A (LHRHa, apalutamide)
arm group type: Experimental
description: Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
arm group type: Experimental
description: Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.
intervention type: Drug
intervention name: Abiraterone Acetate
description: Given PO
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
other name: CB7630
other name: Yonsa
other name: Zytiga
intervention type: Drug
intervention name: Apalutamide
description: Given PO
arm group label: Arm A (LHRHa, apalutamide)
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
other name: ARN 509
other name: ARN-509
other name: ARN509
other name: Erleada
other name: JNJ 56021927
other name: JNJ-56021927
intervention type: Biological
intervention name: Gonadotropin-releasing Hormone Analog
description: Given IM
arm group label: Arm A (LHRHa, apalutamide)
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
other name: GnRH Agonist
other name: GnRH Analog
other name: Gonadotropin-Releasing Hormone Agonist
other name: Gonadotropin-Releasing Hormone Analogue
other name: LH-RH agonist
other name: LH-RH Analogs
other name: LHRH Agonist
other name: luteinizing hormone-releasing hormone agonist
other name: Luteinizing Hormone-Releasing Hormone Analog
intervention type: Drug
intervention name: Prednisone
description: Given PO
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
other name: .delta.1-Cortisone
other name: 1, 2-Dehydrocortisone
other name: Adasone
other name: Cortancyl
other name: Dacortin
other name: DeCortin
other name: Decortisyl
other name: Decorton
other name: Delta 1-Cortisone
other name: Delta-Dome
other name: Deltacortene
other name: Deltacortisone
other name: Deltadehydrocortisone
other name: Deltasone
other name: Deltison
other name: Deltra
other name: Econosone
other name: Lisacort
other name: Meprosona-F
other name: Metacortandracin
other name: Meticorten
other name: Ofisolona
other name: Orasone
other name: Panafcort
other name: Panasol-S
other name: Paracort
other name: Perrigo Prednisone
other name: PRED
other name: Predicor
other name: Predicorten
other name: Prednicen-M
other name: Prednicort
other name: Prednidib
other name: Prednilonga
other name: Predniment
other name: Prednisone Intensol
other name: Prednisonum
other name: Prednitone
other name: Promifen
other name: Rayos
other name: Servisone
other name: SK-Prednisone
intervention type: Procedure
intervention name: Radical Prostatectomy
description: Undergo radical prostatectomy
arm group label: Arm A (LHRHa, apalutamide)
arm group label: Arm B (LHRHa, apalutamide, abiraterone acetate)
other name: Prostatovesiculectomy
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Logothetis
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Cortisone
mesh term: Abiraterone Acetate
mesh term: Hormones
mesh term: Prolactin Release-Inhibiting Factors
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 