<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/NCT03298087</url>
  </required_header>
  <id_info>
    <org_study_id>ONCA-013-16F</org_study_id>
    <nct_id>NCT03298087</nct_id>
  </id_info>
  <brief_title>Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer</brief_title>
  <official_title>Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</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 is a trial for patients with newly diagnosed metastatic prostate cancer with 5 or fewer&#xD;
      sites of metastases. The trial involves surgery (removal of the prostate) or radiation to the&#xD;
      prostate, six months of hormone therapy, and stereotactic body radiotherapy to the sites of&#xD;
      metastasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm Phase II clinical trial in patients with newly diagnosed M1a,b prostate&#xD;
      cancer and 1-5 radiographically visible metastases treated with radical prostatectomy (and&#xD;
      post-operative fractionated radiotherapy for pT 3a, pN1, or positive margins) or radiation to&#xD;
      the prostate, metastasis directed SBRT, and complete ADT with LHRH analog leuprolide,&#xD;
      abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of&#xD;
      systemic therapy. The primary endpoint of our study is the percent of patients achieving a&#xD;
      serum PSA of &lt;0.05 ng/mL six months after recovery of serum testosterone (for patients&#xD;
      undergoing radical prostatectomy) or PSA &lt;nadir+2 (for patients undergoing prostate&#xD;
      radiation).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</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>
    <intervention_model_description>Single arm Phase II clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PSA&lt;0.05ng/mL (radical prostatectomy) or PSA &lt;nadir+2ng/mL (prostate radiation)</measure>
    <time_frame>6 months after recovery of testosterone</time_frame>
    <description>PSA is a biomarker for disease burden in prostate adenocarcinoma and offers a non-invasive and sensitive assessment of disease control after treatment in the vast majority of patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>time to biochemical progression</measure>
    <time_frame>up to 5 years</time_frame>
    <description>biochemical, radiographic, or clinical</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to radiographic progression</measure>
    <time_frame>up to 5 years</time_frame>
    <description>per PCWG3 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to initiation of additional antineoplastic therapy</measure>
    <time_frame>up to 5 years</time_frame>
    <description>antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate cancer specific survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Prostate cancer specific survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcomes as assedded by Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire</measure>
    <time_frame>up to 5 years</time_frame>
    <description>This uses the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire. It assesses patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Items are rated on a 0 to 4 Likert type scale and combined to produce subscale scores for each domain and a global score, the higher the score, the better the quality of life. Range from 0-150 . Data will be aggregated per patient and over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by physician using CTCAE v4.0 criteria</measure>
    <time_frame>up to 5 years</time_frame>
    <description>CTCAE v4 criteria are a set of criteria for the standardized classification of adverse effects cancer therapy. The CTCAE system is a product of the US National Cancer Institute. The criteria are assessed by physician. The grades range from 0 to 5 (higher is worse). Data will be aggregated per patient and over time and classified by organ system (e.g., genitourinary, gastrointestinal, etc).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Newly Diagnosed Oligometastatic Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Experimental Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radical prostatectomy (and post-operative fractionated radiotherapy for pT=3a, pN1, or positive margins), metastasis directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>radical prostatectomy</intervention_name>
    <description>surgical removal of the prostate</description>
    <arm_group_label>Experimental Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>stereotactic body radiotherapy</intervention_name>
    <description>Highly targeted radiation</description>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>SBRT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leuprolide</intervention_name>
    <description>Lowers serum testosterone</description>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>ADT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>apalutamide</intervention_name>
    <description>antiandrogen</description>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>ARN-509</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>abiraterone</intervention_name>
    <description>Inhibits androgen synthesis</description>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>zytiga</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Biopsy confirmed diagnosis of prostate adenocarcinoma (primary small cell carcinoma of&#xD;
             the prostate is not allowed, however adenocarcinoma with neuroendocrine&#xD;
             differentiation is allowed)&#xD;
&#xD;
          2. Age 18&#xD;
&#xD;
          3. Presence of 1-5 visible metastases (by NaF PET-CT or PSMA PET-CT including diagnostic&#xD;
             CT of the chest, abdomen, and pelvis)&#xD;
&#xD;
               1. At least one metastasis must be M1a-b&#xD;
&#xD;
               2. Visceral metastases are not allowed&#xD;
&#xD;
               3. Patients may have any number of pelvic nodal metastases (but largest must be &lt;2&#xD;
                  cm)&#xD;
&#xD;
               4. Metastases must be amenable to treatment with SBRT&#xD;
&#xD;
               5. Biopsy of one metastasis must be attempted, unless unsafe to perform. If biopsy&#xD;
                  is not diagnostic, or unsafe to perform, then a secondary imaging modality (for&#xD;
                  example, MRI) must also be consistent with metastatic disease (unless PSMA PET-CT&#xD;
                  was used as initial staging).&#xD;
&#xD;
          4. Patient must be fit to undergo radical prostatectomy, SBRT to all visible sites of&#xD;
             metastases, ADT,&#xD;
&#xD;
          5. Total testosterone &gt;200 ng/dL prior to ADT (optimal time to measure total testosterone&#xD;
             is between 8 and 9 am)&#xD;
&#xD;
          6. Adequate performance status (ECOG 0-1)&#xD;
&#xD;
          7. Clinical laboratory values at screening:&#xD;
&#xD;
               1. Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3&#xD;
                  months prior to randomization&#xD;
&#xD;
               2. Platelet count 100,000 x 109/ L independent of transfusion and/or growth factors&#xD;
                  within 3 months prior to randomization&#xD;
&#xD;
               3. Serum albumin 3.0 g/dL&#xD;
&#xD;
               4. GFR 45 mL/min&#xD;
&#xD;
               5. Serum potassium 3.5 mmol/L&#xD;
&#xD;
               6. Serum total bilirubin 1.5 ULN (Note: In subjects with Gilbert's syndrome, if&#xD;
                  total bilirubin is &gt;1.5 ULN, measure direct and indirect bilirubin and if direct&#xD;
                  bilirubin is 1.5 ULN, subject may be eligible)&#xD;
&#xD;
               7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &lt;2.5 ULN&#xD;
&#xD;
          8. Medications known to lower the seizure threshold (see list under prohibited&#xD;
             medications) must be discontinued or substituted at least 4 weeks prior to study&#xD;
             entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any evidence of spinal cord compression (radiological or clinical)&#xD;
&#xD;
          2. Prior pelvic malignancy&#xD;
&#xD;
          3. Prior pelvic radiation&#xD;
&#xD;
          4. Concurrent malignancy aside from superficial skin cancers or superficial bladder&#xD;
             tumors&#xD;
&#xD;
          5. Inability to undergo prostatectomy, radiotherapy, or ADT&#xD;
&#xD;
          6. Primary small cell carcinoma of the prostate (prostate adenocarcinoma with&#xD;
             neuroendocrine differentiation is allowed)&#xD;
&#xD;
          7. Inflammatory bowel disease or active collagen vascular disease&#xD;
&#xD;
          8. History of any of the following:&#xD;
&#xD;
               1. Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke&#xD;
                  within 1year to randomization, brain arteriovenous malformation, Schwannoma,&#xD;
                  meningioma, or other benign CNS or meningeal disease which may require treatment&#xD;
                  with surgery or radiation therapy)&#xD;
&#xD;
               2. Severe or unstable angina, myocardial infarction, symptomatic congestive heart&#xD;
                  failure, arterial or venous thromboembolic events (eg, pulmonary embolism,&#xD;
                  cerebrovascular accident including transient ischemic attacks), or clinically&#xD;
                  significant ventricular arrhythmias within 6 months prior to randomization&#xD;
&#xD;
          9. Current evidence of any of the following:&#xD;
&#xD;
               1. Uncontrolled hypertension&#xD;
&#xD;
               2. Gastrointestinal disorder affecting absorption&#xD;
&#xD;
               3. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)&#xD;
&#xD;
               4. Any chronic medical condition requiring a higher dose of corticosteroid than 10&#xD;
                  mg prednisone/prednisolone once daily&#xD;
&#xD;
               5. Any condition that in the opinion of the investigator would preclude&#xD;
                  participation in this study&#xD;
&#xD;
               6. Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be&#xD;
                  co-administered, abiraterone acetate dose frequency will be adjusted).&#xD;
&#xD;
               7. Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an&#xD;
                  alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate&#xD;
                  may be considered.&#xD;
&#xD;
               8. Baseline severe hepatic impairment (ChildPugh Class B &amp; C)&#xD;
&#xD;
         10. Presence of visceral metastases (i.e., stage M1c)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Prostate cancer only affects males.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicholas George Nickols, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Greater Los Angeles Healthcare System, West Los Angeles, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Long Beach Healthcare System, Long Beach, CA</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Greater Los Angeles Healthcare System, West Los Angeles, CA</name>
      <address>
        <city>West Los Angeles</city>
        <state>California</state>
        <zip>90073-1003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hunter Holmes McGuire VA Medical Center, Richmond, VA</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oligometastatic</keyword>
  <keyword>SBRT</keyword>
  <keyword>abiraterone</keyword>
  <keyword>apalutamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leuprolide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03298087
org study id: ONCA-013-16F
nct id: NCT03298087
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a trial for patients with newly diagnosed metastatic prostate cancer with 5 or fewer
      sites of metastases. The trial involves surgery (removal of the prostate) or radiation to the
      prostate, six months of hormone therapy, and stereotactic body radiotherapy to the sites of
      metastasis.
This is a single arm Phase II clinical trial in patients with newly diagnosed M1a,b prostate
      cancer and 1-5 radiographically visible metastases treated with radical prostatectomy (and
      post-operative fractionated radiotherapy for pT 3a, pN1, or positive margins) or radiation to
      the prostate, metastasis directed SBRT, and complete ADT with LHRH analog leuprolide,
      abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of
      systemic therapy. The primary endpoint of our study is the percent of patients achieving a
      serum PSA of <0.05 ng/mL six months after recovery of serum testosterone (for patients
      undergoing radical prostatectomy) or PSA <nadir+2 (for patients undergoing prostate
      radiation).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm Phase II clinical trial
primary purpose: Treatment
masking: None (Open Label)
measure: PSA<0.05ng/mL (radical prostatectomy) or PSA <nadir+2ng/mL (prostate radiation)
time frame: 6 months after recovery of testosterone
description: PSA is a biomarker for disease burden in prostate adenocarcinoma and offers a non-invasive and sensitive assessment of disease control after treatment in the vast majority of patients.
measure: time to biochemical progression
time frame: up to 5 years
description: biochemical, radiographic, or clinical
measure: Time to radiographic progression
time frame: up to 5 years
description: per PCWG3 criteria
measure: Time to initiation of additional antineoplastic therapy
time frame: up to 5 years
description: antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy
measure: Prostate cancer specific survival
time frame: up to 5 years
description: Prostate cancer specific survival
measure: Patient reported outcomes as assedded by Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
time frame: up to 5 years
description: This uses the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire. It assesses patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Items are rated on a 0 to 4 Likert type scale and combined to produce subscale scores for each domain and a global score, the higher the score, the better the quality of life. Range from 0-150 . Data will be aggregated per patient and over time.
measure: Number of participants with treatment-related adverse events as assessed by physician using CTCAE v4.0 criteria
time frame: up to 5 years
description: CTCAE v4 criteria are a set of criteria for the standardized classification of adverse effects cancer therapy. The CTCAE system is a product of the US National Cancer Institute. The criteria are assessed by physician. The grades range from 0 to 5 (higher is worse). Data will be aggregated per patient and over time and classified by organ system (e.g., genitourinary, gastrointestinal, etc).
arm group label: Experimental Arm
arm group type: Experimental
description: Radical prostatectomy (and post-operative fractionated radiotherapy for pT=3a, pN1, or positive margins), metastasis directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy.
intervention type: Procedure
intervention name: radical prostatectomy
description: surgical removal of the prostate
arm group label: Experimental Arm
intervention type: Radiation
intervention name: stereotactic body radiotherapy
description: Highly targeted radiation
arm group label: Experimental Arm
other name: SBRT
intervention type: Drug
intervention name: Leuprolide
description: Lowers serum testosterone
arm group label: Experimental Arm
other name: ADT
intervention type: Drug
intervention name: apalutamide
description: antiandrogen
arm group label: Experimental Arm
other name: ARN-509
intervention type: Drug
intervention name: abiraterone
description: Inhibits androgen synthesis
arm group label: Experimental Arm
other name: zytiga
criteria: 
gender: Male
gender based: Yes
gender description: Prostate cancer only affects males.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicholas George Nickols, MD PhD
role: Principal Investigator
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Leuprolide
sharing ipd: No