<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/NCT01685125</url>
  </required_header>
  <id_info>
    <org_study_id>4P-12-1</org_study_id>
    <secondary_id>NCI-2012-01485</secondary_id>
    <nct_id>NCT01685125</nct_id>
  </id_info>
  <brief_title>Abiraterone Acetate and Prednisone With or Without Dasatinib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer</brief_title>
  <official_title>A Randomized Phase II Trial of Dasatinib Plus Abiraterone Compared to Abiraterone Alone for Metastatic, Castration-Resistant Prostate Cancer Prior to Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well giving abiraterone acetate and prednisone with or&#xD;
      without dasatinib works in treating patients with metastatic, hormone-resistant prostate&#xD;
      cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as&#xD;
      abiraterone acetate, may lessen the amount of androgens made by the body. Dasatinib may stop&#xD;
      the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not&#xD;
      yet known whether abiraterone acetate and prednisone is more effective than abiraterone&#xD;
      acetate, prednisone, and dasatinib in treating prostate cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the progression-free survival of men with metastatic castration-resistant&#xD;
      prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men&#xD;
      treated with abiraterone alone.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To describe the toxicity profile of the combination, as well as the rate of&#xD;
      prostate-specific antigen (PSA) response, objective responses, and changes in circulating&#xD;
      tumor cell (CTC) numbers.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive&#xD;
      abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily&#xD;
      (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients&#xD;
      also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence&#xD;
      of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">March 2018</completion_date>
  <primary_completion_date type="Actual">March 2016</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 (PFS)</measure>
    <time_frame>From the start of abiraterone acetate until first evidence of disease progression or until death from any cause, whichever occurs first, assessed up to 3 years</time_frame>
    <description>PFS defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A one-sided, 0.05-level log rank test will be used to compare the two arms in terms of PFS. PFS will be estimated using the product-limit method of Kaplan and Meier.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Overall response defined as the percent of subjects whose best response is a complete response or partial response based on RECIST version 1.1. Exact 95% confidence intervals will be calculated for this estimate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA change response according to PSA Working Group Criteria 2</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>PSA changes will be summarized for each arm also using waterfall plots as well as standard descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From start of abiraterone acetate and/or dasatinib treatment until death due to any cause or time the patient was last known to be alive, assessed up to 3 years</time_frame>
    <description>Estimated using the product-limit method of Kaplan and Meier. The probability of remaining alive at 6, 12, 18 and 24 months, with the associated Greenwood's standard errors, will be summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intent-to-treat analysis</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Hormone-resistant Prostate Cancer</condition>
  <condition>Recurrent Prostate Cancer</condition>
  <condition>Stage IV Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A (abiraterone acetate, prednisone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Abiraterone acetate 1000 mg PO QD and Prednisone 5 mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (abiraterone acetate, prednisone, dasatinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Abiraterone acetate 1000 mg PO QD, Prednisone 5 mg PO BID, and dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks 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>Arm A (abiraterone acetate, prednisone)</arm_group_label>
    <arm_group_label>Arm B (abiraterone acetate, prednisone, dasatinib)</arm_group_label>
    <other_name>CB7630</other_name>
    <other_name>Zytiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dasatinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (abiraterone acetate, prednisone, dasatinib)</arm_group_label>
    <other_name>BMS-354825</other_name>
    <other_name>Sprycel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prednisone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (abiraterone acetate, prednisone)</arm_group_label>
    <arm_group_label>Arm B (abiraterone acetate, prednisone, dasatinib)</arm_group_label>
    <other_name>DeCortin</other_name>
    <other_name>Deltra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic, castration-resistant prostate cancer&#xD;
&#xD;
               -  Defined as evaluable radiographic disease with rising PSA x 2 (at least 1 week&#xD;
                  apart) or radiographic progression (new soft tissue/bone lesions or enlarging&#xD;
                  soft tissue lesions) despite medical or surgical castration&#xD;
&#xD;
               -  No limit on prior hormonal therapies (i.e. anti-androgens, ketoconazole) except&#xD;
                  that subject must not have received abiraterone previously&#xD;
&#xD;
               -  No limit on prior biologic therapies (i.e. immune therapy, antiangiogenic,&#xD;
                  targeted) except that patient should not have received dasatinib or other v-src&#xD;
                  sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (src)-targeted&#xD;
                  therapy&#xD;
&#xD;
          -  No prior chemotherapy for metastatic disease&#xD;
&#xD;
             * Subjects who have received chemotherapy in the neoadjuvant or adjuvant setting will&#xD;
             be eligible provided chemotherapy was completed &gt; 6 months prior to enrollment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) 0-2&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 times the institutional upper limit of normal (ULN) except for&#xD;
             Gilbert's syndrome&#xD;
&#xD;
          -  Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ) =&lt;&#xD;
             2.5 times the institutional ULN&#xD;
&#xD;
          -  Serum sodium (Na), potassium (K+), magnesium (Mg+), phosphate and calcium (Ca+) &gt;&#xD;
             lower limit of normal (LLN)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 time the institutional ULN&#xD;
&#xD;
          -  Hemoglobin (Hb) &gt;= 9&#xD;
&#xD;
          -  Platelets &gt;= 100,000&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000&#xD;
&#xD;
          -  Ability to take oral medication (study medications must be swallowed whole)&#xD;
&#xD;
          -  Men with fathering potential must agree to use contraception throughout study&#xD;
             treatment; acceptable methods include: condoms, sponge, intrauterine device (IUD),&#xD;
             oral contraceptives&#xD;
&#xD;
          -  Concomitant medications * Patient agrees to discontinue St. Johns wort while receiving&#xD;
             dasatinib therapy (discontinue St. Johns wort at least 5 days before starting&#xD;
             dasatinib)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hepatitis B or C or human immunodeficiency virus (HIV), regardless of viral load&#xD;
&#xD;
             * Testing for the purposes of enrollment is not mandatory, however a documented&#xD;
             history of these infections will be exclusionary due to concerns for drug-drug&#xD;
             interactions with antivirals and potential for increased risk of liver toxicity&#xD;
&#xD;
          -  Radiation for palliation of bony metastases within the preceding 2 weeks&#xD;
&#xD;
          -  Prior chemotherapy for metastatic castration-resistant prostate cancer (CRPC)&#xD;
&#xD;
             * Immune therapy with sipuleucel-T is allowed, provided the last infusion was &gt;= 28&#xD;
             days prior to study therapy and there has been at least one documented PSA value&#xD;
             rising after completion of sipuleucel-T therapy or progression of disease on imaging&#xD;
             after sipuleucel-T&#xD;
&#xD;
          -  Malignancy (aside from prostate cancer) which required radiotherapy or systemic&#xD;
             treatment within the past 5 years&#xD;
&#xD;
               -  Superficial bladder cancer treated with intravesical therapy and currently in&#xD;
                  remission will not be an exclusion&#xD;
&#xD;
               -  Skin cancers will not be an exclusion, except for melanoma with a thickness &gt; 1&#xD;
                  mm&#xD;
&#xD;
          -  Concurrent medical condition which may increase the risk of toxicity, including:&#xD;
&#xD;
               -  Pleural or pericardial effusion of any grade at the time of study entry&#xD;
&#xD;
               -  Cardiac symptoms; any of the following should be considered for exclusion: **&#xD;
                  Uncontrolled angina, congestive heart failure or myocardial infarction (MI)&#xD;
                  within (6 months)&#xD;
&#xD;
                    -  Diagnosed congenital long QT syndrome&#xD;
&#xD;
                    -  Any history of clinically significant ventricular arrhythmias (such as&#xD;
                       ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)&#xD;
                       ** Prolonged QTc/f interval on pre-entry electrocardiogram (&gt; 450 msec)&#xD;
&#xD;
                    -  Hypokalemia or hypomagnesemia if it cannot be corrected prior to abiraterone&#xD;
                       administration&#xD;
&#xD;
          -  History of significant bleeding disorder unrelated to cancer, including:&#xD;
&#xD;
               -  Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)&#xD;
&#xD;
               -  Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor&#xD;
                  VIII antibodies)&#xD;
&#xD;
               -  Ongoing or recent (=&lt; 3 months) significant gastrointestinal bleeding&#xD;
&#xD;
          -  Prohibited treatments and/or therapies&#xD;
&#xD;
               -  Should not be on any additional anti-cancer therapy except for luteinizing&#xD;
                  hormone-releasing hormone (LHRH) agonist/antagonist; specifically excluded&#xD;
                  medications include ketoconazole, estrogens, and anti-androgens&#xD;
&#xD;
               -  Category I drugs that are generally accepted to have a risk of causing Torsades&#xD;
                  de pointes including: (Patients must discontinue drug 7 days prior to starting&#xD;
                  dasatinib)&#xD;
&#xD;
                    -  Quinidine, procainamide, disopyramide&#xD;
&#xD;
                    -  Amiodarone, sotalol, ibutilide, dofetilide&#xD;
&#xD;
                    -  Erythromycin, clarithromycin&#xD;
&#xD;
                    -  Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide&#xD;
&#xD;
                    -  Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,&#xD;
                       domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,&#xD;
                       lidoflazine&#xD;
&#xD;
          -  Prisoners or subjects who are involuntarily incarcerated&#xD;
&#xD;
          -  Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (eg, infectious disease) illness&#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>Tanya Dorff</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <last_update_submitted>July 5, 2017</last_update_submitted>
  <last_update_submitted_qc>July 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2017</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>Dasatinib</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/NCT01685125
org study id: 4P-12-1
secondary id: NCI-2012-01485
nct id: NCT01685125
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II trial studies how well giving abiraterone acetate and prednisone with or
      without dasatinib works in treating patients with metastatic, hormone-resistant prostate
      cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as
      abiraterone acetate, may lessen the amount of androgens made by the body. Dasatinib may stop
      the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not
      yet known whether abiraterone acetate and prednisone is more effective than abiraterone
      acetate, prednisone, and dasatinib in treating prostate cancer
PRIMARY OBJECTIVES:

      I. To compare the progression-free survival of men with metastatic castration-resistant
      prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men
      treated with abiraterone alone.

      SECONDARY OBJECTIVES:

      I. To describe the toxicity profile of the combination, as well as the rate of
      prostate-specific antigen (PSA) response, objective responses, and changes in circulating
      tumor cell (CTC) numbers.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive
      abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily
      (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or
      unacceptable toxicity.

      ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients
      also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence
      of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS)
time frame: From the start of abiraterone acetate until first evidence of disease progression or until death from any cause, whichever occurs first, assessed up to 3 years
description: PFS defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A one-sided, 0.05-level log rank test will be used to compare the two arms in terms of PFS. PFS will be estimated using the product-limit method of Kaplan and Meier.
measure: Overall response
time frame: Up to 3 years
description: Overall response defined as the percent of subjects whose best response is a complete response or partial response based on RECIST version 1.1. Exact 95% confidence intervals will be calculated for this estimate.
measure: PSA change response according to PSA Working Group Criteria 2
time frame: Baseline and 12 weeks
description: PSA changes will be summarized for each arm also using waterfall plots as well as standard descriptive statistics.
measure: Overall survival
time frame: From start of abiraterone acetate and/or dasatinib treatment until death due to any cause or time the patient was last known to be alive, assessed up to 3 years
description: Estimated using the product-limit method of Kaplan and Meier. The probability of remaining alive at 6, 12, 18 and 24 months, with the associated Greenwood's standard errors, will be summarized.
measure: Intent-to-treat analysis
time frame: Up to 3 years
arm group label: Arm A (abiraterone acetate, prednisone)
arm group type: Active Comparator
description: Abiraterone acetate 1000 mg PO QD and Prednisone 5 mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
arm group label: Arm B (abiraterone acetate, prednisone, dasatinib)
arm group type: Experimental
description: Abiraterone acetate 1000 mg PO QD, Prednisone 5 mg PO BID, and dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: abiraterone acetate
description: Given PO
arm group label: Arm A (abiraterone acetate, prednisone)
arm group label: Arm B (abiraterone acetate, prednisone, dasatinib)
other name: CB7630
other name: Zytiga
intervention type: Drug
intervention name: dasatinib
description: Given PO
arm group label: Arm B (abiraterone acetate, prednisone, dasatinib)
other name: BMS-354825
other name: Sprycel
intervention type: Drug
intervention name: prednisone
description: Given PO
arm group label: Arm A (abiraterone acetate, prednisone)
arm group label: Arm B (abiraterone acetate, prednisone, dasatinib)
other name: DeCortin
other name: Deltra
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tanya Dorff
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Dasatinib
mesh term: Abiraterone Acetate