<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/NCT02215161</url>
  </required_header>
  <id_info>
    <org_study_id>14552</org_study_id>
    <secondary_id>NCI-2014-01936</secondary_id>
    <secondary_id>14-13390</secondary_id>
    <secondary_id>14552</secondary_id>
    <nct_id>NCT02215161</nct_id>
  </id_info>
  <brief_title>Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer</brief_title>
  <official_title>Phase II Single Agent Study of Selinexor (KPT-330) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Prior Therapy With Abiraterone and/or Enzalutamide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</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 California, San Francisco</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies selinexor in treating patients with prostate cancer that has&#xD;
      spread to other parts of the body (metastatic), keeps growing even when the amount of&#xD;
      testosterone in the body is reduced to very low levels (castration-resistant), and did not&#xD;
      respond to treatment (refractory) with abiraterone acetate and/or enzalutamide. Selinexor may&#xD;
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To describe radiographic progression free survival (rPFS) associated with selinexor in&#xD;
      patients with abiraterone (abiraterone acetate) refractory metastatic castration-resistant&#xD;
      prostate cancer (mCRPC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To measure prostate-specific antigen (PSA) changes at 12 weeks post-selinexor initiation.&#xD;
&#xD;
      II. To assess time to PSA progression. III. To measure time to development of &gt;= 2 new bone&#xD;
      lesions. IV. To compare the relationship of abiraterone-resistance status (primary vs&#xD;
      acquired) and treatment outcome.&#xD;
&#xD;
      V. To determine the effect of selinexor on persistent pain associated with bone metastasis&#xD;
      using the brief pain inventory (BPI) short form.&#xD;
&#xD;
      VI. To describe the safety profile of selinexor in patients with metastatic&#xD;
      castration-resistant prostate cancer.&#xD;
&#xD;
      VII. To determine the effect of selinexor on circulating leukocyte exportin 1 (XPO-1)&#xD;
      expression, leukocyte gene expression profile and macrophage inhibitory cytokine-1 (MIC-1)&#xD;
      messenger ribonucleic acid (mRNA) expression.&#xD;
&#xD;
      VIII. To assess serum selinexor trough levels as a function of dose and time since last dose.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To describe the relationship of XPO-1 expression to PSA decline. II. To describe the&#xD;
      expression profile of metastatic tumor and outcome. III. To describe the type of progression&#xD;
      (e.g. pain, bone etc). IV. To define XPO-1 expression in patients for whom pre- and&#xD;
      post-treatment biopsy is obtained.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive selinexor orally (PO) on days 1 and 3 of weeks 1-3. Courses repeat every 28&#xD;
      days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days and then every 6&#xD;
      months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Risk to benefit ratio is not acceptable&#xD;
  </why_stopped>
  <start_date type="Actual">September 2, 2014</start_date>
  <completion_date type="Actual">April 2, 2018</completion_date>
  <primary_completion_date type="Actual">February 15, 2017</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>Radiographic Progression Free Survival (rPFS)</measure>
    <time_frame>From study start up to 3 years</time_frame>
    <description>Defined as the time from study start until one of the following events occurs: &gt;= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Abiraterone Resistance Status (Primary Versus Acquired)</measure>
    <time_frame>At baseline</time_frame>
    <description>Comparison of radiographic progression free survival between patients with primary abiraterone resistance and acquired abiraterone resistance using a Cox proportional hazards model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA Progression</measure>
    <time_frame>Time between the first evaluation at which the response criteria are met and the first documentation of PSA progression or death or up to 3 years</time_frame>
    <description>Time between the first evaluation at which the response criteria are met and the first documentation of PSA (Prostate-Specific Antigen) progression or death. Progression is defined as a rise in PSA of 50% above nadir value or 25% above baseline if there is no decline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Non-serious Adverse Events</measure>
    <time_frame>Up to 3 years after treatment start</time_frame>
    <description>Incidence of non-serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment</measure>
    <time_frame>On days 1 and 15 of course 1 and on day 1 of courses 2 and 3</time_frame>
    <description>Total RNA isolated from leukocytes of patients will be used for quantitative polymerase chain reaction analysis (qPCR) in order to compare expression levels of XPO-1 and MIC-1 as a function of selinexor dose and total time on treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation</measure>
    <time_frame>At 12 weeks post therapy initiation</time_frame>
    <description>The number of patients experiencing a PSA decline from baseline of at least 50% in PSA at 12 weeks following the initiation of study therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Pain for Symptomatic Patients, Measured Using the Brief Pain Inventory (BPI), Short Form</measure>
    <time_frame>At baseline and day 1 of every following cycle until end of treatment or 3 years after study start</time_frame>
    <description>The effect of selinexor on persistent pain associated with bone metastasis, measured using the Brief Pain Inventory (BPI), Short Form. 0 denotes ''no pain'' and 10, ''pain as bad as you can imagine&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Selinexor Levels</measure>
    <time_frame>At day 1 of course 1, each treatment day until end of treatment up to 3 years</time_frame>
    <description>Serum selinexor trough levels as a function of dose and time since last dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Confirmed Development of &gt;= 2 New Bone Lesions That Cannot be Attributable to Bone Scan Flare</measure>
    <time_frame>At week 8, 16, 24, and every 12 weeks thereafter up to 3 years after treatment start</time_frame>
    <description>Defined as time interval between the date of treatment initiation and the date of documented new lesions. Evaluation criteria is defined by the PSAWG2 (Prostate-Specific Antigen Working Group 2) criteria for bone scan evaluation. The time will be 'backdated' to when the &gt;= 2 new lesions were detected if a second scan is done to confirm progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Serious Adverse Events</measure>
    <time_frame>Up to 3 years after treatment start</time_frame>
    <description>Incidence of serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Castration Levels of Testosterone</condition>
  <condition>Hormone-Resistant Prostate Cancer</condition>
  <condition>Metastatic Prostate Carcinoma in the Soft Tissue</condition>
  <condition>Prostate Carcinoma Metastatic in the Bone</condition>
  <condition>PSA Progression</condition>
  <condition>Stage IV Prostate Adenocarcinoma AJCC v7</condition>
  <arm_group>
    <arm_group_label>Treatment (selinexor)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive selinexor PO on days 1 and 3 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selinexor</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (selinexor)</arm_group_label>
    <other_name>CRM1 Nuclear Export Inhibitor KPT-330</other_name>
    <other_name>KPT-330</other_name>
    <other_name>Selective Inhibitor of Nuclear Export KPT-330</other_name>
    <other_name>SINE KPT-330</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the prostate&#xD;
&#xD;
          -  Patients must have castrate levels of testosterone (&lt; 50 ng/dL) on&#xD;
             gonadotropin-releasing hormone (GnRH) analogues or have had prior orchiectomy; GnRH&#xD;
             analogues must be continued while on study&#xD;
&#xD;
          -  Tumor tissue submitted for molecular and genetic analysis through the companion&#xD;
             Stand-up 2 Cancer (SU2C) radiologically guided biopsy of abiraterone and/or&#xD;
             enzalutamide refractory mCRPC protocol&#xD;
&#xD;
               -  Patients who consent to participate in the companion biopsy protocol and are&#xD;
                  subsequently determined to be ineligible for biopsy are eligible to participate&#xD;
                  in the current protocol&#xD;
&#xD;
          -  Progressive disease as demonstrated by a rising PSA (at least two determinations)&#xD;
             prior to study entry, and/or radiographic evidence of tumor progression in soft tissue&#xD;
             according to modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria&#xD;
             or identification of new lesions by bone scan (i.e., &gt;= 2 new lesions)&#xD;
&#xD;
          -  Primary resistance or acquired resistance (i.e., acquired resistance will be defined&#xD;
             as disease progression following a period of response defined as &gt;= 50% decline in PSA&#xD;
             within 12 weeks of starting therapy and not otherwise meeting criteria for primary&#xD;
             resistance) to any of the following agents/combinations of therapy:&#xD;
&#xD;
          -  Abiraterone acetate; primary resistance to abiraterone will be defined as:&#xD;
&#xD;
               -  No PSA decline&#xD;
&#xD;
               -  PSA decline less than 50% after 12 weeks of abiraterone therapy&#xD;
&#xD;
               -  PSA progression within 12 weeks of abiraterone acetate (AA) treatment (by&#xD;
                  Prostate Cancer Working Group-2 [PCWG2] criteria), after initial response to&#xD;
                  therapy&#xD;
&#xD;
               -  Objective progression, by RECIST criteria for soft tissue lesions and by modified&#xD;
                  PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone treatment&#xD;
&#xD;
               -  Unequivocal clinical progression (per the treating provider's discretion) within&#xD;
                  12 weeks of starting abiraterone treatment&#xD;
&#xD;
          -  Enzalutamide; primary resistance to enzalutamide will be defined as:&#xD;
&#xD;
               -  No PSA decline&#xD;
&#xD;
               -  PSA decline less than 50% after 12 weeks of enzalutamide therapy&#xD;
&#xD;
               -  PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria),&#xD;
                  after initial response to therapy&#xD;
&#xD;
               -  Objective progression, by RECIST criteria for soft tissue lesions and by modified&#xD;
                  PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide&#xD;
                  treatment&#xD;
&#xD;
               -  Unequivocal clinical progression (per the treating provider's discretion) within&#xD;
                  12 weeks of starting enzalutamide treatment&#xD;
&#xD;
          -  Other second-generation investigational anti-androgen/androgen-receptor targeted&#xD;
             therapies, including apalutamide (ARN-509); primary resistance will be defined as:&#xD;
&#xD;
               -  No PSA decline&#xD;
&#xD;
               -  PSA decline less than 50% after 12 weeks of enzalutamide therapy&#xD;
&#xD;
               -  PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria),&#xD;
                  after initial response to therapy&#xD;
&#xD;
               -  Objective progression, by RECIST criteria for soft tissue lesions and by modified&#xD;
                  PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide&#xD;
                  treatment&#xD;
&#xD;
               -  Unequivocal clinical progression (per the treating provider's discretion) within&#xD;
                  12 weeks of starting enzalutamide treatment&#xD;
&#xD;
          -  Combination therapy with abiraterone, enzalutamide and/or other second- generation&#xD;
             investigational anti-androgen/androgen-receptor targeted therapies, including ARN-509;&#xD;
             primary resistance to combination therapy will be defined as:&#xD;
&#xD;
               -  No PSA decline&#xD;
&#xD;
               -  PSA decline less than 50% after 12 weeks of abiraterone and enzalutamide therapy&#xD;
&#xD;
               -  PSA progression within 12 weeks of abiraterone and enzalutamide treatment (by&#xD;
                  PCWG2 criteria), after initial response to therapy&#xD;
&#xD;
               -  Objective progression, by RECIST criteria for soft tissue lesions and by modified&#xD;
                  PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone and&#xD;
                  enzalutamide treatment&#xD;
&#xD;
               -  Unequivocal clinical progression (per the treating provider?s discretion) within&#xD;
                  12 weeks of starting abiraterone and enzalutamide treatment&#xD;
&#xD;
          -  Sequenced therapy, including any of the following:&#xD;
&#xD;
               -  Abiraterone acetate followed by enzalutamide&#xD;
&#xD;
                    -  Primary resistance will be defined per criteria for abiraterone monotherapy&#xD;
                       primary resistance&#xD;
&#xD;
               -  Enzalutamide followed by abiraterone acetate&#xD;
&#xD;
                    -  Primary resistance will be defined per criteria for enzalutamide monotherapy&#xD;
                       primary resistance&#xD;
&#xD;
               -  Other second-generation investigational anti-androgen/androgen- receptor targeted&#xD;
                  therapies, including ARN-509&#xD;
&#xD;
                    -  Primary resistance will be defined per criteria for other investigational&#xD;
                       anti-androgen monotherapy primary resistance&#xD;
&#xD;
          -  Presence of 1 or more bone metastasis&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Prior and ongoing zoledronic acid or denosumab therapy is allowed&#xD;
&#xD;
          -  Prior therapy with radium-223 is allowed&#xD;
&#xD;
          -  Discontinuation of prior therapy for mCRPC: a washout period of 28 days for the&#xD;
             following therapies is required: abiraterone, enzalutamide, fluconazole, itraconazole,&#xD;
             flutamide, bicalutamide, nilutamide, and other experimental hormonal agents (ARN509,&#xD;
             orteronel [TAK-700], etc.), sipuleucel-T (Provenge), other experimental vaccines&#xD;
             (PROSTVAC-V/F, etc.), strontium-89, samarium, and radium-223 chloride&#xD;
&#xD;
          -  Leukocytes &gt; 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt; 125,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 5.59 mmol/L or 9 g/dL; up to 5% deviation is tolerated; transfusions and&#xD;
             growth factors are allowed&#xD;
&#xD;
          -  Total bilirubin within normal institutional limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) &lt; 3 X&#xD;
             institutional upper limit of normal&#xD;
&#xD;
          -  Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) &lt; 3 X&#xD;
             institutional upper limit of normal&#xD;
&#xD;
          -  Creatinine within normal institutional limits OR creatinine clearance &gt; 60 mL/min/1.73&#xD;
             m^2 for patients with creatinine levels above institutional normal&#xD;
&#xD;
          -  Ability to understand a written informed consent document, and the willingness to sign&#xD;
             it&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Able to swallow and retain oral medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Untreated brain metastases; brain metastases =&lt; 1 cm and not associated with any focal&#xD;
             neurologic deficits are allowed&#xD;
&#xD;
          -  Prior docetaxel or other chemotherapy for mCRPC; patients who have received docetaxel&#xD;
             for metastatic hormone-sensitive prostate cancer are eligible&#xD;
&#xD;
          -  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, or New&#xD;
             York Heart Association (NYHA) class II-IV heart disease or known cardiac ejection&#xD;
             fraction measurement of &lt; 50 % at baseline&#xD;
&#xD;
          -  Patients with significantly diseased or obstructed gastrointestinal tract or&#xD;
             uncontrolled vomiting or diarrhea or other gastrointestinal disorders (medical&#xD;
             disorders or extensive surgery) that may interfere with the absorption of the study&#xD;
             agents&#xD;
&#xD;
          -  Pure small cell carcinoma of the prostate or any mixed histology cancer of the&#xD;
             prostate (eg: neuroendocrine) that contains &lt; 50% adenocarcinoma, as observed on&#xD;
             biopsy obtained at the time of diagnosis or on any subsequent biopsies&#xD;
&#xD;
          -  Any ?currently active? second malignancy, other than non-melanoma skin cancer;&#xD;
             patients are not considered to have a &quot;currently active? malignancy, if they have&#xD;
             completed therapy and are considered by their physician to be at least less than 30%&#xD;
             risk of relapse over next year&#xD;
&#xD;
          -  Any condition, which in the opinion of the investigator, would preclude participation&#xD;
             in this trial&#xD;
&#xD;
          -  Active psychiatric illnesses/social situations that would limit compliance with&#xD;
             protocol requirements&#xD;
&#xD;
          -  Patients in whom urgent treatment with docetaxel is indicated, per clinician&#xD;
             discretion; this includes, but is not limited to patients with symptomatic visceral&#xD;
             metastatic disease&#xD;
&#xD;
          -  Uncontrolled infection or concomitant medical illness that is not adequately&#xD;
             controlled with current medical management, as determined per clinician discretion&#xD;
&#xD;
          -  Active bleeding disorders or evidence of evidence of chronic or acute disseminated&#xD;
             intravascular coagulation (DIC)&#xD;
&#xD;
          -  Severely compromised immunological state, including known human immunodeficiency virus&#xD;
             (HIV)&#xD;
&#xD;
          -  Any acute toxicities due to prior anti-cancer treatments and/or radiotherapy that have&#xD;
             not resolved to a National Cancer Institute (NCI) Common Terminology Criteria for&#xD;
             Adverse Events (CTCAE) grade of =&lt; 1 (except alopecia)&#xD;
&#xD;
          -  Prior radiation therapy completed &lt; 3 weeks or single fraction of palliative&#xD;
             radiotherapy &lt; 14 days prior to first dose of KPT-330 (selinexor)&#xD;
&#xD;
          -  Initiation of bisphosphonate therapy &lt; 4 weeks prior to first dose of KPT-330;&#xD;
             patients receiving bisphosphonate or denosumab therapy must be on stable doses for at&#xD;
             least 4 weeks prior to first dose of KPT-330&#xD;
&#xD;
          -  Men unable or unwilling to employ 2 forms of highly effective contraception throughout&#xD;
             the study and for 8 weeks after the end of study treatment&#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>Charles Ryan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <results_first_submitted>April 26, 2018</results_first_submitted>
  <results_first_submitted_qc>May 29, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 26, 2018</results_first_posted>
  <last_update_submitted>May 29, 2018</last_update_submitted>
  <last_update_submitted_qc>May 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2018</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>
  <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>April 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT02215161/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Selinexor)</title>
          <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
Ondansetron 8 mg PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
Olanzapine 5 mg PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Selinexor)</title>
          <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
Ondansetron 8 mg PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
Olanzapine 5 mg PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age Group</title>
              <category_list>
                <category>
                  <title>50 - 59</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>60 - 69</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>70 - 79</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Radiographic Progression Free Survival (rPFS)</title>
        <description>Defined as the time from study start until one of the following events occurs: &gt;= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.</description>
        <time_frame>From study start up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Progression Free Survival (rPFS)</title>
          <description>Defined as the time from study start until one of the following events occurs: &gt;= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" lower_limit="7" upper_limit="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Abiraterone Resistance Status (Primary Versus Acquired)</title>
        <description>Comparison of radiographic progression free survival between patients with primary abiraterone resistance and acquired abiraterone resistance using a Cox proportional hazards model.</description>
        <time_frame>At baseline</time_frame>
        <population>The study was terminated due to unacceptable toxicity. Data on resistance type was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Primary Abiraterone Resistance</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Aquired Abiraterone Resistance</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Abiraterone Resistance Status (Primary Versus Acquired)</title>
          <description>Comparison of radiographic progression free survival between patients with primary abiraterone resistance and acquired abiraterone resistance using a Cox proportional hazards model.</description>
          <population>The study was terminated due to unacceptable toxicity. Data on resistance type was not 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 PSA Progression</title>
        <description>Time between the first evaluation at which the response criteria are met and the first documentation of PSA (Prostate-Specific Antigen) progression or death. Progression is defined as a rise in PSA of 50% above nadir value or 25% above baseline if there is no decline.</description>
        <time_frame>Time between the first evaluation at which the response criteria are met and the first documentation of PSA progression or death or up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to PSA Progression</title>
          <description>Time between the first evaluation at which the response criteria are met and the first documentation of PSA (Prostate-Specific Antigen) progression or death. Progression is defined as a rise in PSA of 50% above nadir value or 25% above baseline if there is no decline.</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="7" upper_limit="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Non-serious Adverse Events</title>
        <description>Incidence of non-serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
        <time_frame>Up to 3 years after treatment start</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Non-serious Adverse Events</title>
          <description>Incidence of non-serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anorexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypophosphatemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypocalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight loss</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>INR increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigations - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal distension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flatulence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Localized edema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood and lymphatic system disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bone pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain in extremity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arthralgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Musculoskeletal/connective tissue disorder, other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Presyncope</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypotension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hot flashes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blurred vision</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Night blindness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Watering eyes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lung infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Upper respiratory infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Psychosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cough</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Voice alteration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiac disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chest pain - cardiac</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alopecia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematuria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment</title>
        <description>Total RNA isolated from leukocytes of patients will be used for quantitative polymerase chain reaction analysis (qPCR) in order to compare expression levels of XPO-1 and MIC-1 as a function of selinexor dose and total time on treatment.</description>
        <time_frame>On days 1 and 15 of course 1 and on day 1 of courses 2 and 3</time_frame>
        <population>The study was terminated due to unacceptable toxicity. Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Selinexor Day 1, Course 1</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Selinexor Day 15, Course 1</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Selinexor Day 1, Course 2</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O4">
            <title>Selinexor Day 1, Course 3</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment</title>
          <description>Total RNA isolated from leukocytes of patients will be used for quantitative polymerase chain reaction analysis (qPCR) in order to compare expression levels of XPO-1 and MIC-1 as a function of selinexor dose and total time on treatment.</description>
          <population>The study was terminated due to unacceptable toxicity. Data was not 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 group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation</title>
        <description>The number of patients experiencing a PSA decline from baseline of at least 50% in PSA at 12 weeks following the initiation of study therapy.</description>
        <time_frame>At 12 weeks post therapy initiation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation</title>
          <description>The number of patients experiencing a PSA decline from baseline of at least 50% in PSA at 12 weeks following the initiation of study therapy.</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reduction in Pain for Symptomatic Patients, Measured Using the Brief Pain Inventory (BPI), Short Form</title>
        <description>The effect of selinexor on persistent pain associated with bone metastasis, measured using the Brief Pain Inventory (BPI), Short Form. 0 denotes ''no pain'' and 10, ''pain as bad as you can imagine&quot;.</description>
        <time_frame>At baseline and day 1 of every following cycle until end of treatment or 3 years after study start</time_frame>
        <population>The study was terminated due to unacceptable toxicity. Only baseline data was collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Pain at Baseline</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Pain at Day 1, Course 2 and Following Courses</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction in Pain for Symptomatic Patients, Measured Using the Brief Pain Inventory (BPI), Short Form</title>
          <description>The effect of selinexor on persistent pain associated with bone metastasis, measured using the Brief Pain Inventory (BPI), Short Form. 0 denotes ''no pain'' and 10, ''pain as bad as you can imagine&quot;.</description>
          <population>The study was terminated due to unacceptable toxicity. Only baseline data was collected.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.34" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Selinexor Levels</title>
        <description>Serum selinexor trough levels as a function of dose and time since last dose</description>
        <time_frame>At day 1 of course 1, each treatment day until end of treatment up to 3 years</time_frame>
        <population>The study was terminated due to unacceptable toxicity. Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Selinexor Levels</title>
          <description>Serum selinexor trough levels as a function of dose and time since last dose</description>
          <population>The study was terminated due to unacceptable toxicity. Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Confirmed Development of &gt;= 2 New Bone Lesions That Cannot be Attributable to Bone Scan Flare</title>
        <description>Defined as time interval between the date of treatment initiation and the date of documented new lesions. Evaluation criteria is defined by the PSAWG2 (Prostate-Specific Antigen Working Group 2) criteria for bone scan evaluation. The time will be 'backdated' to when the &gt;= 2 new lesions were detected if a second scan is done to confirm progression.</description>
        <time_frame>At week 8, 16, 24, and every 12 weeks thereafter up to 3 years after treatment start</time_frame>
        <population>The study was terminated due to unacceptable toxicity. Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Confirmed Development of &gt;= 2 New Bone Lesions That Cannot be Attributable to Bone Scan Flare</title>
          <description>Defined as time interval between the date of treatment initiation and the date of documented new lesions. Evaluation criteria is defined by the PSAWG2 (Prostate-Specific Antigen Working Group 2) criteria for bone scan evaluation. The time will be 'backdated' to when the &gt;= 2 new lesions were detected if a second scan is done to confirm progression.</description>
          <population>The study was terminated due to unacceptable toxicity. Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Serious Adverse Events</title>
        <description>Incidence of serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
        <time_frame>Up to 3 years after treatment start</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Selinexor)</title>
            <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
8mg Ondansetron PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
5mg Olanzapine PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- 60mg Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Serious Adverse Events</title>
          <description>Incidence of serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye disorders - Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years, 6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Selinexor)</title>
          <description>BID: twice a day D: day PO: oral 1 cycle = 4 weeks, 28 days&#xD;
Premedication:&#xD;
Ondansetron 8 mg PO every 8 hours on day prior to and day of dosing (D0-D3)&#xD;
Olanzapine 5 mg PO at bedtime or 2.5 mg PO BID on day of dosing (D1, D3)&#xD;
Study drug:&#xD;
- Selinexor PO on D1 and D3 of weeks 1-3 of each cycle. Drug holiday on week 4. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="13" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Night blindness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Psychosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Voice alteration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="14"/>
              </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>
    <limitations_and_caveats>The study was terminated due to unacceptable toxicity.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Charles Ryan, MD</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>877-827-3222</phone>
      <email>clinicaltrials@ucsf.edu</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/NCT02215161
org study id: 14552
secondary id: NCI-2014-01936
secondary id: 14-13390
secondary id: 14552
nct id: NCT02215161
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase II trial studies selinexor in treating patients with prostate cancer that has
      spread to other parts of the body (metastatic), keeps growing even when the amount of
      testosterone in the body is reduced to very low levels (castration-resistant), and did not
      respond to treatment (refractory) with abiraterone acetate and/or enzalutamide. Selinexor may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:

      I. To describe radiographic progression free survival (rPFS) associated with selinexor in
      patients with abiraterone (abiraterone acetate) refractory metastatic castration-resistant
      prostate cancer (mCRPC).

      SECONDARY OBJECTIVES:

      I. To measure prostate-specific antigen (PSA) changes at 12 weeks post-selinexor initiation.

      II. To assess time to PSA progression. III. To measure time to development of >= 2 new bone
      lesions. IV. To compare the relationship of abiraterone-resistance status (primary vs
      acquired) and treatment outcome.

      V. To determine the effect of selinexor on persistent pain associated with bone metastasis
      using the brief pain inventory (BPI) short form.

      VI. To describe the safety profile of selinexor in patients with metastatic
      castration-resistant prostate cancer.

      VII. To determine the effect of selinexor on circulating leukocyte exportin 1 (XPO-1)
      expression, leukocyte gene expression profile and macrophage inhibitory cytokine-1 (MIC-1)
      messenger ribonucleic acid (mRNA) expression.

      VIII. To assess serum selinexor trough levels as a function of dose and time since last dose.

      TERTIARY OBJECTIVES:

      I. To describe the relationship of XPO-1 expression to PSA decline. II. To describe the
      expression profile of metastatic tumor and outcome. III. To describe the type of progression
      (e.g. pain, bone etc). IV. To define XPO-1 expression in patients for whom pre- and
      post-treatment biopsy is obtained.

      OUTLINE:

      Patients receive selinexor orally (PO) on days 1 and 3 of weeks 1-3. Courses repeat every 28
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days and then every 6
      months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Radiographic Progression Free Survival (rPFS)
time frame: From study start up to 3 years
description: Defined as the time from study start until one of the following events occurs: >= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.
measure: Abiraterone Resistance Status (Primary Versus Acquired)
time frame: At baseline
description: Comparison of radiographic progression free survival between patients with primary abiraterone resistance and acquired abiraterone resistance using a Cox proportional hazards model.
measure: Time to PSA Progression
time frame: Time between the first evaluation at which the response criteria are met and the first documentation of PSA progression or death or up to 3 years
description: Time between the first evaluation at which the response criteria are met and the first documentation of PSA (Prostate-Specific Antigen) progression or death. Progression is defined as a rise in PSA of 50% above nadir value or 25% above baseline if there is no decline.
measure: Incidence of Non-serious Adverse Events
time frame: Up to 3 years after treatment start
description: Incidence of non-serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
measure: Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment
time frame: On days 1 and 15 of course 1 and on day 1 of courses 2 and 3
description: Total RNA isolated from leukocytes of patients will be used for quantitative polymerase chain reaction analysis (qPCR) in order to compare expression levels of XPO-1 and MIC-1 as a function of selinexor dose and total time on treatment.
measure: PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation
time frame: At 12 weeks post therapy initiation
description: The number of patients experiencing a PSA decline from baseline of at least 50% in PSA at 12 weeks following the initiation of study therapy.
measure: Reduction in Pain for Symptomatic Patients, Measured Using the Brief Pain Inventory (BPI), Short Form
time frame: At baseline and day 1 of every following cycle until end of treatment or 3 years after study start
description: The effect of selinexor on persistent pain associated with bone metastasis, measured using the Brief Pain Inventory (BPI), Short Form. 0 denotes ''no pain'' and 10, ''pain as bad as you can imagine".
measure: Serum Selinexor Levels
time frame: At day 1 of course 1, each treatment day until end of treatment up to 3 years
description: Serum selinexor trough levels as a function of dose and time since last dose
measure: Time to Confirmed Development of >= 2 New Bone Lesions That Cannot be Attributable to Bone Scan Flare
time frame: At week 8, 16, 24, and every 12 weeks thereafter up to 3 years after treatment start
description: Defined as time interval between the date of treatment initiation and the date of documented new lesions. Evaluation criteria is defined by the PSAWG2 (Prostate-Specific Antigen Working Group 2) criteria for bone scan evaluation. The time will be 'backdated' to when the >= 2 new lesions were detected if a second scan is done to confirm progression.
measure: Incidence of Serious Adverse Events
time frame: Up to 3 years after treatment start
description: Incidence of serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
arm group label: Treatment (selinexor)
arm group type: Experimental
description: Patients receive selinexor PO on days 1 and 3 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Selinexor
description: Given PO
arm group label: Treatment (selinexor)
other name: CRM1 Nuclear Export Inhibitor KPT-330
other name: KPT-330
other name: Selective Inhibitor of Nuclear Export KPT-330
other name: SINE KPT-330
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charles Ryan, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Prostatic Neoplasms
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated due to unacceptable toxicity.
point of contact: 