<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/NCT02218606</url>
  </required_header>
  <id_info>
    <org_study_id>14-046</org_study_id>
    <secondary_id>PCCTC LOI: c12-108</secondary_id>
    <nct_id>NCT02218606</nct_id>
  </id_info>
  <brief_title>Multicenter Trial of Abiraterone Acetate With or Without Cabazitaxel in Treatment of Metastatic Castration Resistant Prostate Cancer</brief_title>
  <official_title>An Exploratory Randomized Phase II Multicenter Trial of Abiraterone Acetate With or Without Cabazitaxel in Treatment of Metastatic Castration Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see what effects (good and bad) treatment with abiraterone&#xD;
      acetate (an oral hormonal agent) and prednisone (a steroid) with and without cabazitaxel (a&#xD;
      chemotherapy) have on the cancer and to find out more about whether specific laboratory tests&#xD;
      on tumor are useful in predicting how the patient will respond to treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</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>progression free survival (rPFS)</measure>
    <time_frame>1 year</time_frame>
    <description>using the RECIST criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PSA progression free survival (PSA PFS)</measure>
    <time_frame>1 year</time_frame>
    <description>For each patient, use a waterfall plot to report the percent change in PSA from baseline to 12 weeks (or earlier for those who discontinue therapy) and the maximum decline in PSA that occurs at any point after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>objective response rate (ORR)</measure>
    <time_frame>1 year</time_frame>
    <description>per RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>toxicity</measure>
    <time_frame>1 year</time_frame>
    <description>The NCI CTCAE version 4.0 will be used for recording and grading AEs.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1: Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 2: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abiraterone acetate 1000 mg po daily</intervention_name>
    <arm_group_label>Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID</arm_group_label>
    <arm_group_label>Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabazitaxel 25 mg/m2 IV</intervention_name>
    <arm_group_label>Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prednisone 5 mg po BID</intervention_name>
    <arm_group_label>Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID</arm_group_label>
    <arm_group_label>Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient needs to have a histologic or cytologic diagnosis of prostate cancer&#xD;
&#xD;
        Documented progressive metastatic CRPC based on at least one of the following criteria:&#xD;
&#xD;
          1. PSA progression defined as 25% increase over baseline value with an increase in the&#xD;
             absolute value of at least 2 ng/mL that is confirmed by another PSA level with a&#xD;
             minimum of a 1 week interval and a minimum PSA of 2 ng/mL.&#xD;
&#xD;
          2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the LD of all&#xD;
             target lesions based on the smallest sum LD since treatment started or the appearance&#xD;
             of one or more new lesions.&#xD;
&#xD;
          3. Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.&#xD;
&#xD;
               -  Agree to undergo a biopsy of at least one metastatic site or primary prostate for&#xD;
                  determination of the RB status. Adequate archival metastatic tissue can be used&#xD;
                  if available in lieu of a biopsy if done when patient had CRPC (within 6 months&#xD;
                  of treatment start).&#xD;
&#xD;
               -  ECOG performance status of 0-2.&#xD;
&#xD;
               -  Age ≥ 18 years.&#xD;
&#xD;
               -  Have testosterone &lt; 50 ng/dL. Patients must continue primary androgen deprivation&#xD;
                  with an LHRH/GnRH analogue (agonist or antagonist) if they have not undergone&#xD;
                  orchiectomy.&#xD;
&#xD;
               -  Patients on long term (&gt;6 months) anti-androgen therapy (e.g. flutamide,&#xD;
                  bicalutamide, nilutamide) will need to be off anti-androgen for 4 weeks (wash out&#xD;
                  period) and show evidence of disease progression off the anti-androgen. Patients&#xD;
                  that have been on an anti-androgen 6 months or less will need to discontinue&#xD;
                  anti-androgen therapy prior to treatment start (no wash out period required).&#xD;
&#xD;
               -  Patients must have adequate organ and marrow function as defined below obtained&#xD;
                  within 14 days prior to treatment start:&#xD;
&#xD;
               -  ANC &gt;=1,500/μl&#xD;
&#xD;
               -  Hemoglobin &gt;=9g/dL&#xD;
&#xD;
               -  Platelet count &gt;=100,000/μl&#xD;
&#xD;
               -  Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  Potassium &gt; 3.5 mmol/L (within institutional normal range)&#xD;
&#xD;
               -  Bilirubin ≤ ULN (unless documented Gilbert's disease)&#xD;
&#xD;
               -  SGOT (AST) &lt;=2.5 x ULN&#xD;
&#xD;
               -  SGPT (ALT) &lt;=2.5 x ULN&#xD;
&#xD;
               -  The effects of cabazitaxel and abiraterone acetate on the developing human fetus&#xD;
                  at the recommended therapeutic dose are unknown. Men must agree to use adequate&#xD;
                  contraception prior to study entry, for the duration of study participation and&#xD;
                  for at least 3 months thereafter.&#xD;
&#xD;
               -  Patients must be able to take oral medication without crushing, dissolving or&#xD;
                  chewing tablets.&#xD;
&#xD;
               -  Patients may have received prior radiation therapy or major surgery. However, at&#xD;
                  least 21 days prior to treatment start must have elapsed since completion of&#xD;
                  radiation therapy or major surgery and patient must have recovered from all side&#xD;
                  effects at the time of randomization.&#xD;
&#xD;
               -  Ability to understand and the willingness to sign a written informed consent&#xD;
                  document that is approved by the local institutional review board.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents. Any prior&#xD;
             investigational therapeutic products must be stopped at least 28 days (4 week washout)&#xD;
             prior to treatment start.&#xD;
&#xD;
          -  No prior exposure to abiraterone acetate or other specific CYP-17 inhibitors.&#xD;
&#xD;
          -  No prior chemotherapy regimen. Prior isotope therapy with Strontium-89, Samarium or&#xD;
             RAD223 should be completed at least three months (12 weeks) prior to treatment start.&#xD;
&#xD;
          -  No ≥ grade 2 peripheral neuropathy&#xD;
&#xD;
          -  Patients who have had antifungal agents (itraconazole, fluconazole) within 4 weeks&#xD;
             prior to treatment start or those who have not recovered from AEs due to these agents&#xD;
             administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Patients with a history of pituitary or adrenal dysfunction, active or symptomatic&#xD;
             viral hepatitis or chronic liver disease are not eligible.&#xD;
&#xD;
          -  Patients with known symptomatic brain metastases should be excluded from this clinical&#xD;
             trial because of their poor prognosis and because they often develop progressive&#xD;
             neurologic dysfunction that would confound the evaluation of neurologic and other AEs.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to cabazitaxel or other drugs formulated with polysorbate 80; or&#xD;
             abiraterone acetate.&#xD;
&#xD;
          -  Patients may continue on a daily Multi-Vitamin, calcium and Vitamin D, but all other&#xD;
             herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort,&#xD;
             etc.) must be discontinued before treatment start. Patients must not be planning to&#xD;
             receive any concurrent cytotoxic chemotherapy, surgery for their prostate cancer, or&#xD;
             radiation therapy during protocol treatment.&#xD;
&#xD;
          -  Patients on stable doses of bisphosphonates or the RANK-L inhibitor, Denosumab, which&#xD;
             have been started no less than 4 weeks prior to treatment start, may continue on this&#xD;
             medication, however patients are not allowed to initiate bisphosphonate/Denosumab&#xD;
             therapy during the study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure (New York Heart Association Class III&#xD;
             and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric&#xD;
             illness/social situations that, in the opinion of the investigator, would limit&#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>Susan Slovin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Oncology Associates</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</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 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Abiraterone Acetate</keyword>
  <keyword>CABAZITAXEL</keyword>
  <keyword>CASTRATION RESISTANT</keyword>
  <keyword>14-046</keyword>
  <keyword>Prostate Cancer Clinical Trials Consortium</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>Prednisone</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/NCT02218606
org study id: 14-046
secondary id: PCCTC LOI: c12-108
nct id: NCT02218606
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to see what effects (good and bad) treatment with abiraterone
      acetate (an oral hormonal agent) and prednisone (a steroid) with and without cabazitaxel (a
      chemotherapy) have on the cancer and to find out more about whether specific laboratory tests
      on tumor are useful in predicting how the patient will respond to treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression free survival (rPFS)
time frame: 1 year
description: using the RECIST criteria
measure: PSA progression free survival (PSA PFS)
time frame: 1 year
description: For each patient, use a waterfall plot to report the percent change in PSA from baseline to 12 weeks (or earlier for those who discontinue therapy) and the maximum decline in PSA that occurs at any point after treatment.
measure: objective response rate (ORR)
time frame: 1 year
description: per RECIST criteria
measure: toxicity
time frame: 1 year
description: The NCI CTCAE version 4.0 will be used for recording and grading AEs.
arm group label: Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID
arm group type: Experimental
description: Arm 1: Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID
arm group label: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily
arm group type: Experimental
description: Arm 2: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID
intervention type: Drug
intervention name: Abiraterone acetate 1000 mg po daily
arm group label: Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID
arm group label: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily
intervention type: Drug
intervention name: Cabazitaxel 25 mg/m2 IV
arm group label: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily
intervention type: Drug
intervention name: prednisone 5 mg po BID
arm group label: Abiraterone acetate 1000 mg po daily + prednisone 5 mg po BID
arm group label: Cabazitaxel 25 mg/m2 IV + abiraterone acetate 1000 mg po daily
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Susan Slovin, MD, PhD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Abiraterone Acetate