<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/NCT03821792</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0533</org_study_id>
    <secondary_id>NCI-2018-03599</secondary_id>
    <secondary_id>2018-0533</secondary_id>
    <nct_id>NCT03821792</nct_id>
  </id_info>
  <brief_title>Abiraterone Acetate, Prednisone, and Apalutamide in Treating Patients With Hormone-Naive Metastatic Prostate Cancer</brief_title>
  <official_title>A Phase 2 Course Determining Study for Men With Hormone-Naïve Metastatic Prostate Cancer (HNMPCa)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well abiraterone acetate, prednisone, and apalutamide work in&#xD;
      treating patients with hormone-naive prostate cancer that has spread to other places in the&#xD;
      body. Androgen can cause the growth of prostate cancer cells. Antihormone therapy, such as&#xD;
      abiraterone acetate and apalutamide may lessen the amount of androgen made by the body.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine if a baseline molecular-pathologic androgen receptor response (AR-response)&#xD;
      signature predicts efficacy to abiraterone plus apalutamide in patients with hormone-naive&#xD;
      metastatic prostate cancer (HNMPCa).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate the efficacy of abiraterone acetate plus apalutamide in patients with HNMPCa.&#xD;
&#xD;
      II. Evaluate the safety of abiraterone acetate plus apalutamide in patients with HNMPCa.&#xD;
&#xD;
      III. Explore the relationship between molecular markers and clinical efficacy outcomes.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patient receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and&#xD;
      apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and then for up to 6&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 22, 2019</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time on treatment</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Calculated as the time from start of protocol treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Time from starting treatment until progression, assessed up to 6 months</time_frame>
    <description>Median PFS and 95% confidence interval will be presented for all patients and by the androgen receptor molecular-pathologic responsiveness signature.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy assessed</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>prostate specific antigen, bone specific alkaline phosphatase, and urine n-telopeptides</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of candidate markers</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Candidate markers for different biologic domains by immunohistochemistry, mass spectrometry (for steroid metabolome) and genomic profiling. Markers will encompass bone remodeling (e.g. integrin signaling), steroid metabolome (e.g. glucocorticoid receptor) and tumor immunoprofile (e.g. PD-1, PDL-1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 6 months</time_frame>
    <description>Time from start of protocol treatment until death or last contact</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Metastatic Prostate Carcinoma</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <condition>Prostate Carcinoma Metastatic in the Bone</condition>
  <condition>Stage IV Prostate Cancer AJCC v8</condition>
  <condition>Stage IVA Prostate Cancer AJCC v8</condition>
  <condition>Stage IVB Prostate Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (abiraterone acetate, prednisone, apalutamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abiraterone Acetate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (abiraterone acetate, prednisone, apalutamide)</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>Treatment (abiraterone acetate, prednisone, apalutamide)</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>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (abiraterone acetate, prednisone, apalutamide)</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed adenocarcinoma of the prostate&#xD;
&#xD;
          -  At least 2 of the 3 following high-risk prognostic factors:&#xD;
&#xD;
               -  Gleason score of &gt;= 8&#xD;
&#xD;
               -  Presence of 3 or more lesions on bone scan&#xD;
&#xD;
               -  Presence of measurable visceral (excluding lymph node disease) metastasis on&#xD;
                  computed tomography (CT) or magnetic resonance imaging (MRI) (Response Evaluation&#xD;
                  Criteria in Solid Tumors [RECIST] 1.1)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 2&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL independent of transfusion and/or growth factors within 3&#xD;
             months prior to enrollment&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/uL independent of transfusion and/or growth factors within 3&#xD;
             months prior to enrollment&#xD;
&#xD;
          -  Serum albumin &gt;= 3.0 g/dL&#xD;
&#xD;
          -  Medications known to lower the seizure threshold must be discontinued or substituted&#xD;
             at least 4 weeks prior to study entry&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mm^3&#xD;
&#xD;
          -  Calculated creatinine clearance (Cockcroft-Gault equation) &gt;= 45 mL/min&#xD;
&#xD;
          -  Serum potassium &gt;= 3.5 mEg/L&#xD;
&#xD;
          -  Serum magnesium &gt;= 1.6 mg/dL&#xD;
&#xD;
          -  Serum bilirubin &lt; 1.5 x institutional upper limit of normal (IULN) (except for&#xD;
             patients with known Gilbert's disease if total bilirubin is &gt; 1.5 x ULN, measure&#xD;
             direct and indirect bilirubin and if direct bilirubin is =&lt; 1.5 x ULN, subject may be&#xD;
             eligible)&#xD;
&#xD;
          -  Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &lt; 2.5 x IULN&#xD;
             for patients without liver metastases. (Note: In subjects with Gilbert's syndrome, if&#xD;
             total bilirubin is &gt; 1.5 x ULN, measure direct and indirect bilirubin and if direct&#xD;
             bilirubin is =&lt; 1.5 x ULN, subject may be eligible. For patients with liver metastases&#xD;
             AST or ALT &lt; 4 x IULN is allowed)&#xD;
&#xD;
          -  Able to swallow study drugs whole as a tablet/capsule&#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;
          -  Patients must agree to tissue collection for correlative studies at the specified time&#xD;
             points&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Small cell prostate cancer&#xD;
&#xD;
          -  Treatment within 28 days of cycle 1 day 1: Any prior pharmacotherapy, radiation&#xD;
             therapy, or surgery for metastatic prostate cancer. The following exceptions are&#xD;
             permitted:&#xD;
&#xD;
               -  Up to 3 months of antiandrogen therapy (ADT) with LHRH agonists or antagonists or&#xD;
                  orchiectomy with or without concurrent anti-androgens prior to cycle 1 day 1.&#xD;
                  Anti-androgens (flutamide, bicalutamide or nilutamide) for subjects receiving an&#xD;
                  LHRH agonist must be discontinued within 2 weeks of cycle 1 day 1, or subjects&#xD;
                  may have one course of palliative radiation or surgical therapy to treat symptoms&#xD;
                  resulting from metastatic disease (e.g., impending cord compression or&#xD;
                  obstructive symptoms) if it was administered at least 28 days prior to cycle 1&#xD;
                  day 1. All adverse events associated with these procedures must be resolved at&#xD;
                  least to grade 1 by cycle 1 day 1, or&#xD;
&#xD;
          -  Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg&#xD;
             prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and topical&#xD;
             steroids are acceptable, as is a short course (i.e. =&lt; 1 day) of corticosteroids to&#xD;
             prevent a reaction to the intravenous (IV) contrast used for CT scans&#xD;
&#xD;
          -  Active infection (requiring oral or IV antibiotics or antiviral therapy) or other&#xD;
             medical condition that would make prednisone/prednisolone (corticosteroid) use&#xD;
             contraindicated. Known history of testing positive for human immunodeficiency virus&#xD;
             (HIV) or known acquired immunodeficiency syndrome (AIDS)&#xD;
&#xD;
          -  A malignancy (other than the one treated in this study) which required radiotherapy or&#xD;
             systemic treatment within the past 5 years, or has a &gt;= 30% probability of recurrence&#xD;
             within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)&#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;
          -  Prolonged corrected QT interval by Fridericia's formula (QTcF) interval on pre-entry&#xD;
             electrocardiogram (&gt;= 450 msec)&#xD;
&#xD;
          -  Known active or symptomatic viral hepatitis or chronic liver disease&#xD;
&#xD;
          -  Clinically significant heart disease as evidenced by myocardial infarction, or&#xD;
             arterial thrombotic events in the past 6 months, severe or unstable angina, history of&#xD;
             clinically significant ventricular arrhythmias (such as ventricular tachycardia,&#xD;
             ventricular fibrillation, or Torsade de pointes), New York Heart Association class&#xD;
             III-IV heart disease or cardiac ejection fraction measurement of &lt; 40% at baseline&#xD;
&#xD;
          -  Patients who have had a history of illness which put them at current risk for bowel&#xD;
             perforation such as acute diverticulitis, intra-abdominal abscess, gastrointestinal&#xD;
             (GI) obstruction and abdominal carcinomatosis&#xD;
&#xD;
          -  Baseline moderate and severe hepatic impairment (Child Pugh class B &amp; C)&#xD;
&#xD;
          -  Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1&#xD;
             year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or&#xD;
             other benign central nervous system [CNS] or meningeal disease which may require&#xD;
             treatment with surgery or radiation therapy)&#xD;
&#xD;
          -  Gastrointestinal disorder affecting absorption&#xD;
&#xD;
          -  Untreated symptomatic spinal cord compression&#xD;
&#xD;
          -  Any underlying medical or psychiatric condition, which in the opinion of the&#xD;
             investigator, will make the administration of study drug hazardous or obscure the&#xD;
             interpretation of adverse events&#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>Paul Corn</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>M Anderson Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <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>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03821792
org study id: 2018-0533
secondary id: NCI-2018-03599
secondary id: 2018-0533
nct id: NCT03821792
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well abiraterone acetate, prednisone, and apalutamide work in
      treating patients with hormone-naive prostate cancer that has spread to other places in the
      body. Androgen can cause the growth of prostate cancer cells. Antihormone therapy, such as
      abiraterone acetate and apalutamide may lessen the amount of androgen made by the body.
PRIMARY OBJECTIVES:

      I. Determine if a baseline molecular-pathologic androgen receptor response (AR-response)
      signature predicts efficacy to abiraterone plus apalutamide in patients with hormone-naive
      metastatic prostate cancer (HNMPCa).

      SECONDARY OBJECTIVES:

      I. Evaluate the efficacy of abiraterone acetate plus apalutamide in patients with HNMPCa.

      II. Evaluate the safety of abiraterone acetate plus apalutamide in patients with HNMPCa.

      III. Explore the relationship between molecular markers and clinical efficacy outcomes.

      OUTLINE:

      Patient receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and
      apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then for up to 6
      months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time on treatment
time frame: Up to 6 months
description: Calculated as the time from start of protocol treatment
measure: Progression free survival (PFS)
time frame: Time from starting treatment until progression, assessed up to 6 months
description: Median PFS and 95% confidence interval will be presented for all patients and by the androgen receptor molecular-pathologic responsiveness signature.
measure: Incidence of adverse events
time frame: Up to 6 months
description: Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
measure: Efficacy assessed
time frame: Up to 6 months
description: prostate specific antigen, bone specific alkaline phosphatase, and urine n-telopeptides
measure: Expression of candidate markers
time frame: Up to 6 months
description: Candidate markers for different biologic domains by immunohistochemistry, mass spectrometry (for steroid metabolome) and genomic profiling. Markers will encompass bone remodeling (e.g. integrin signaling), steroid metabolome (e.g. glucocorticoid receptor) and tumor immunoprofile (e.g. PD-1, PDL-1).
measure: Overall survival
time frame: up to 6 months
description: Time from start of protocol treatment until death or last contact
arm group label: Treatment (abiraterone acetate, prednisone, apalutamide)
arm group type: Experimental
description: Patient receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Abiraterone Acetate
description: Given PO
arm group label: Treatment (abiraterone acetate, prednisone, apalutamide)
other name: CB7630
other name: Yonsa
other name: Zytiga
intervention type: Drug
intervention name: Apalutamide
description: Given PO
arm group label: Treatment (abiraterone acetate, prednisone, apalutamide)
other name: ARN 509
other name: ARN-509
other name: ARN509
other name: Erleada
other name: JNJ 56021927
other name: JNJ-56021927
intervention type: Drug
intervention name: Prednisone
description: Given PO
arm group label: Treatment (abiraterone acetate, prednisone, apalutamide)
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
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Corn
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: M Anderson Cancer Center
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Cortisone
mesh term: Abiraterone Acetate