<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/NCT01695473</url>
  </required_header>
  <id_info>
    <org_study_id>115516</org_study_id>
    <secondary_id>NCI-2013-01830</secondary_id>
    <nct_id>NCT01695473</nct_id>
  </id_info>
  <brief_title>Neoadjuvant BKM120 in High-risk Prostate Cancer</brief_title>
  <official_title>A Pharmacodynamic Study of Pre-prostatectomy BKM120 in Men With High-risk, Localized Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Won Kim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II, study of BKM120 in patients with high-risk, localized prostate cancer.&#xD;
      Eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy of the&#xD;
      prostate to confirm high-risk disease and collect prostate tissue for analysis. Two weeks&#xD;
      after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at&#xD;
      this dose level orally once daily for 14 days prior to radical prostatectomy at University of&#xD;
      California, San Francisco. Radical prostatectomy will be performed on the day of the last&#xD;
      dose of BKM120 at day 14. No further drug will be tken after the radical prostatectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, prospective, pharmacodynamic study of BKM120 in high-risk, localized&#xD;
      prostate cancer. After informed consent and central pathology review of the core prostate&#xD;
      biopsy, eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy&#xD;
      of the prostate to confirm high-risk disease and collect tissue for molecular analysis. Two&#xD;
      weeks after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given&#xD;
      at this dose level orally once daily for 14 days prior to radical prostatectomy at University&#xD;
      of California, San Francisco. Radical prostatectomy will be performed on the day of the last&#xD;
      dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy.&#xD;
&#xD;
      Up to 24 patients, or 21 evaluable patients, will be enrolled through the Department of&#xD;
      Urology or Genitourinary Medical Oncology at the University of California, San Francisco for&#xD;
      this pharmacodynamic study. Toxicity will be assessed during BKM120 administration, and will&#xD;
      involve a clinic visit on Day 14 ± 2 (i.e. before surgery). Follow-up with safety evaluations&#xD;
      will be at 90 ± 7 days post-operatively and involve a toxicity questionnaire, blood tests,&#xD;
      and clinic visit. Toxicity will be monitored and reported using NCI Common Toxicity Criteria&#xD;
      version 4.0 guidelines.&#xD;
&#xD;
      A patient symptom diary will be distributed to each patient at baseline for symptom&#xD;
      self-recording and BKM120 dose self-administration. In addition, a patient identifier card&#xD;
      (wallet-sized) will be distributed to each patient after informed consent and registration.&#xD;
      This information will contain the patient's age, study name and number, investigator and&#xD;
      study coordinator contact information, and expected adverse events that may be present as a&#xD;
      result of BKM120 administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">April 23, 2013</start_date>
  <completion_date type="Actual">February 5, 2015</completion_date>
  <primary_completion_date type="Actual">February 5, 2015</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>Percentage of Participants With Decrease in Phosphorylated S6 Immunohistochemistry (ICH) From Baseline</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Percentage of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration and defined as ≥ 60% decrease in phosphorylated S6 (pS6) from baseline by Immunohistochemistry (IHC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Decrease in 4E-binding protein1 (p4EBP1) Protein Phosphorylation From Baseline</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Percentage of men with downstream target inhibition of phosphatidylinositol 3-kinase (PI3K) in prostate tumor tissue as measured by 4E-binding protein1 (4EBP1) protein phosphorylation immunohistochemistry (IHC) using paired tumor biopsies from before and after drug administration and defined as &gt;= 60% decline in p4EBP1 IHC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Decrease in AKT Protein From Baseline</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>Proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by Protein kinase B (pAKT) IHC determined by a &gt;= 60% decline in pAKT IHC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Displaying Activity of Short Term BKM120 Administration</measure>
    <time_frame>1 Day, immediately prior to surgery</time_frame>
    <description>Activity of short term BKM120 administration in prostate cancer was determined by measured PSA response immediately prior to radical prostatectomy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>High Risk Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant BKM120</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in operating room (OR) scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BKM120</intervention_name>
    <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
    <arm_group_label>Neoadjuvant BKM120</arm_group_label>
    <other_name>Buparlisib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          1. Histologically confirmed adenocarcinoma of the prostate&#xD;
&#xD;
          2. Candidate for radical prostatectomy&#xD;
&#xD;
          3. Prostate cancer with the following pathological characteristics:&#xD;
&#xD;
               1. Gleason sum &gt; 8 AND at least 2 discrete core biopsies containing a minimum of 20%&#xD;
                  cancer or,&#xD;
&#xD;
               2. Gleason pattern 4 + 3 = 7 and greater than 50% of biopsies positive for prostate&#xD;
                  cancer&#xD;
&#xD;
          4. Age &gt;= 18 years&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status &gt; 2&#xD;
&#xD;
          6. Ability to take oral medications (capsule must be swallowed with liquid)&#xD;
&#xD;
          7. Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) &gt;= 1.5 x&#xD;
             109/liter, Platelets ≥ 100 x 109/L, Hemoglobin &gt; 9 grams(g) /decilitre(dL)&#xD;
&#xD;
          8. Total calcium (corrected for serum albumin) within normal limits (biphosphonate use&#xD;
             for malignant hypercalcemia control is not allowed)&#xD;
&#xD;
          9. Magnesium &gt;= the lower limit of normal&#xD;
&#xD;
         10. Potassium within normal limits for the institution&#xD;
&#xD;
         11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal&#xD;
             range&#xD;
&#xD;
         12. Serum bilirubin within normal range (or total bilirubin &lt;= 3.0 x upper limit of normal&#xD;
             (ULN) with direct bilirubin within normal range in patients with well documented&#xD;
             Gilbert Syndrome)&#xD;
&#xD;
         13. Serum creatinine &lt;= 1.5 x upper limit of normal (ULN) or 24-hour clearance &gt;= 50&#xD;
             milliliter per min (mL/min)&#xD;
&#xD;
         14. Serum amylase &lt;= ULN&#xD;
&#xD;
         15. Serum lipase &lt;= ULN&#xD;
&#xD;
         16. Fasting plasma glucose &lt;= 120 mg/dL (6.7 mmol/L)&#xD;
&#xD;
         17. International Normalized Ratio (INR) &lt;= 2&#xD;
&#xD;
         18. Men of reproductive potential and their female partners must use highly effective&#xD;
             contraception during treatment, for 5 half-lives (8 days) after stopping treatment and&#xD;
             for additional 12 weeks (3 months in total after study drug discontinuation) and&#xD;
             should not father a child in this period The highly effective contraception is defined&#xD;
             as either:&#xD;
&#xD;
               1. True abstinence: When this is in line with the preferred and usual lifestyle of&#xD;
                  the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,&#xD;
                  post-ovulation methods) and withdrawal are not acceptable methods of&#xD;
                  contraception.&#xD;
&#xD;
               2. Sterilization: Female partners have had surgical bilateral oophorectomy (with or&#xD;
                  without hysterectomy) or tubal ligation at least six weeks ago. In case of&#xD;
                  oophorectomy alone, only when the reproductive status of the woman has been&#xD;
                  confirmed by follow up hormone level assessment.&#xD;
&#xD;
               3. Male participant sterilization (with the appropriate post-vasectomy documentation&#xD;
                  of the absence of sperm in the ejaculate).&#xD;
&#xD;
               4. Use of a combination of any two of the following (a+b):&#xD;
&#xD;
               5. Female partner with prior placement of an intrauterine device (IUD) or&#xD;
                  intrauterine system (IUS)&#xD;
&#xD;
               6. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or&#xD;
                  cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository •&#xD;
                  Oral contraception use by female partners, injected or implanted hormonal methods&#xD;
                  are not allowed as BKM120 potentially decreases the effectiveness of hormonal&#xD;
                  contraceptives.&#xD;
&#xD;
                    -  Fertile males, defined as all males physiologically capable of conceiving&#xD;
                       offspring must use condom during treatment, for 5 half-lives (8 days) after&#xD;
                       stopping treatment and for additional 12 weeks (3 months in total after&#xD;
                       study drug discontinuation) and should not father a child in this period.&#xD;
&#xD;
         19. Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          1. Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor&#xD;
&#xD;
          2. Known hypersensitivity to BKM120 or to its excipients&#xD;
&#xD;
          3. History of another malignancy within 3 years, except cured basal cell carcinoma of the&#xD;
             skin&#xD;
&#xD;
          4. Hormonal therapy with Gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists&#xD;
             or high dose bicalutamide within 1 month of enrollment unless serum testosterone is&#xD;
             within normal limits.&#xD;
&#xD;
          5. Following mood disorders as judged by the investigator and/or symptom management&#xD;
             service co-investigator, or as a result of patient's mood assessment questionnaire:&#xD;
&#xD;
             • Medically documented history of or active major depressive episode, bipolar disorder&#xD;
             (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt&#xD;
             or ideation, or homicidal ideation (immediate risk of doing harm to others)&#xD;
&#xD;
             • Current &gt;= NCI Common Terminology Criteria for Adverse Events (CTCAE) grade 3&#xD;
             anxiety&#xD;
&#xD;
             • Meets the cut-off score of &gt;= 10 in the Patient Health Questionnaire (PHQ-9) or a&#xD;
             cut-off of &gt;= 15 in the Generalized Anxiety Disorder (GAD-7) mood scale, respectively,&#xD;
             or selects a positive response of &quot;1, 2, or 3&quot; to question number 9 regarding&#xD;
             potential for suicidal thoughts in the PHQ-9 (independent of the total score of the&#xD;
             PHQ-9) will be excluded from the study&#xD;
&#xD;
          6. Current diarrhea &gt;= CTCAE grade 2&#xD;
&#xD;
          7. Active cardiac disease including any of the following:&#xD;
&#xD;
             • History of left ventricular ejection fraction (LVEF) &lt; 50% as determined by Multiple&#xD;
             Grated acquisition (MUGA) scan or echocardiogram (ECHO)&#xD;
&#xD;
             • QTc &gt; 450 msec on screening electrocardiogram (ECG (using the QTcF formula)&#xD;
&#xD;
               -  Angina pectoris that requires the use of anti-anginal medication&#xD;
&#xD;
               -  History of ventricular arrhythmias except for benign premature ventricular&#xD;
                  contractions&#xD;
&#xD;
               -  Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled&#xD;
                  with medication&#xD;
&#xD;
               -  Conduction abnormality requiring a pacemaker&#xD;
&#xD;
               -  Valvular disease with documented compromise in cardiac function&#xD;
&#xD;
               -  Symptomatic pericarditis&#xD;
&#xD;
          8. History of cardiac dysfunction including any of the following:&#xD;
&#xD;
               -  Myocardial infarction within the last 6 months, documented by persistent elevated&#xD;
                  cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF&#xD;
                  function&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III-IV)&#xD;
&#xD;
               -  Documented cardiomyopathy&#xD;
&#xD;
          9. Poorly controlled diabetes mellitus or active, steroid-induced diabetes mellitus&#xD;
&#xD;
         10. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,&#xD;
             active or uncontrolled infection) that could cause unacceptable safety risks or&#xD;
             compromise compliance with the protocol&#xD;
&#xD;
         11. Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea,&#xD;
             vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with&#xD;
             unresolved diarrhea will be excluded as previously indicated&#xD;
&#xD;
         12. Treatment with any hematopoietic colony-stimulating growth factors (G-CSF or GM-CSF)&#xD;
             &lt;= 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if&#xD;
             initiated at least 2 weeks prior to enrollment, may be continued&#xD;
&#xD;
         13. Current treatment with medication with a known risk to prolong the QT interval or&#xD;
             inducing Torsades de Pointes and the treatment cannot either be discontinued or&#xD;
             switched to a different medication prior to starting study drug. Please refer to&#xD;
             section 10.2 for a list of prohibited QT prolonging drugs with risk of Torsades de&#xD;
             Pointes.&#xD;
&#xD;
         14. Current, chronic treatment with steroids or another immunosuppressive agent&#xD;
&#xD;
             • Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways&#xD;
             diseases), eye drops or local injections (e.g. intr-articular) are allowed. If a&#xD;
             patient stops corticosteroids prior to study participation, a 2-week washout is&#xD;
             required.&#xD;
&#xD;
         15. Taking herbal medications and certain fruits and juices within 7 days prior to&#xD;
             starting study drug. Herbal medications include, but are not limited to St. John's&#xD;
             wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe,&#xD;
             saw palmetto, and ginseng. Fruits and juice include the Cytochrome P450 3A (CYP3A)&#xD;
             inhibitors: Seville oranges, grapefruit, and pomelos.&#xD;
&#xD;
         16. Current treatment with drugs known to be moderate and strong inhibitors or inducers of&#xD;
             isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different&#xD;
             medication prior to starting study drug. Please refer to Section 10.2 for a list of&#xD;
             prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak&#xD;
             inhibitors of CYP3A is allowed)&#xD;
&#xD;
         17. Chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea,&#xD;
             antibodies or mitomycin-C) prior to starting study drug&#xD;
&#xD;
         18. Any continuous or intermittent small molecule therapeutics (excluding monoclonal&#xD;
             antibodies) &lt;= 5 effective half lives prior to starting study drug or patients who&#xD;
             have not recovered from side effects of such therapy 19 Major surgery &lt;= 2 weeks prior&#xD;
             to starting study drug or who have not recovered from side effects of such therapy&#xD;
&#xD;
        20. Current treatment with warfarin sodium or any other coumadin-derivative anticoagulant&#xD;
        21. Known diagnosis of human immunodeficiency virus (HIV) infection. Testing is not&#xD;
        required for participation.&#xD;
&#xD;
        22. Unable or unwilling to abide by the study protocol or cooperate fully with the&#xD;
        investigator&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Won Kim, 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>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>December 11, 2020</results_first_submitted>
  <results_first_submitted_qc>January 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 13, 2021</results_first_posted>
  <disposition_first_submitted>May 7, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>May 7, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 8, 2018</disposition_first_posted>
  <last_update_submitted>January 7, 2021</last_update_submitted>
  <last_update_submitted_qc>January 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Won Kim</investigator_full_name>
    <investigator_title>Prinicipal Investigator</investigator_title>
  </responsible_party>
  <keyword>Prostate cancer</keyword>
  <keyword>High-risk prostate cancer</keyword>
  <keyword>Radical prostatectomy</keyword>
  <keyword>BKM120</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Neoadjuvant BKM120</title>
          <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </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>Neoadjuvant BKM120</title>
          <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" lower_limit="53" upper_limit="70"/>
                  </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="11"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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="0"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-treatment Prostate-specific antigen (PSA)</title>
          <units>nanograms per mililiter (ng/mL)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.7" lower_limit="5.7" upper_limit="146.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Decrease in Phosphorylated S6 Immunohistochemistry (ICH) From Baseline</title>
        <description>Percentage of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration and defined as ≥ 60% decrease in phosphorylated S6 (pS6) from baseline by Immunohistochemistry (IHC).</description>
        <time_frame>Up to 3 months</time_frame>
        <population>One patient did not have pretreatment tissue evaluable for IHC</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant BKM120</title>
            <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Decrease in Phosphorylated S6 Immunohistochemistry (ICH) From Baseline</title>
          <description>Percentage of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration and defined as ≥ 60% decrease in phosphorylated S6 (pS6) from baseline by Immunohistochemistry (IHC).</description>
          <population>One patient did not have pretreatment tissue evaluable for IHC</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Decrease in 4E-binding protein1 (p4EBP1) Protein Phosphorylation From Baseline</title>
        <description>Percentage of men with downstream target inhibition of phosphatidylinositol 3-kinase (PI3K) in prostate tumor tissue as measured by 4E-binding protein1 (4EBP1) protein phosphorylation immunohistochemistry (IHC) using paired tumor biopsies from before and after drug administration and defined as &gt;= 60% decline in p4EBP1 IHC</description>
        <time_frame>Up to 3 months</time_frame>
        <population>One patient did not have pretreatment tissue evaluable for IHC</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant BKM120</title>
            <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Decrease in 4E-binding protein1 (p4EBP1) Protein Phosphorylation From Baseline</title>
          <description>Percentage of men with downstream target inhibition of phosphatidylinositol 3-kinase (PI3K) in prostate tumor tissue as measured by 4E-binding protein1 (4EBP1) protein phosphorylation immunohistochemistry (IHC) using paired tumor biopsies from before and after drug administration and defined as &gt;= 60% decline in p4EBP1 IHC</description>
          <population>One patient did not have pretreatment tissue evaluable for IHC</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Decrease in AKT Protein From Baseline</title>
        <description>Proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by Protein kinase B (pAKT) IHC determined by a &gt;= 60% decline in pAKT IHC</description>
        <time_frame>Up to 3 months</time_frame>
        <population>One patient did not have pretreatment tissue evaluable for IHC</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant BKM120</title>
            <description>Twenty four men will receive 2 weeks of daily BKM120 prior to having radical prostatectomy&#xD;
BKM120: Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Decrease in AKT Protein From Baseline</title>
          <description>Proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by Protein kinase B (pAKT) IHC determined by a &gt;= 60% decline in pAKT IHC</description>
          <population>One patient did not have pretreatment tissue evaluable for IHC</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Displaying Activity of Short Term BKM120 Administration</title>
        <description>Activity of short term BKM120 administration in prostate cancer was determined by measured PSA response immediately prior to radical prostatectomy</description>
        <time_frame>1 Day, immediately prior to surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant BKM120</title>
            <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Displaying Activity of Short Term BKM120 Administration</title>
          <description>Activity of short term BKM120 administration in prostate cancer was determined by measured PSA response immediately prior to radical prostatectomy</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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 3 months</time_frame>
      <desc>All adverse events, with severity/grading as determined by the NCI Common Terminology Criteria for Adverse Events (CTCAE).</desc>
      <group_list>
        <group group_id="E1">
          <title>Neoadjuvant BKM120</title>
          <description>Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.</description>
        </group>
      </group_list>
      <serious_events>
        <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="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </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 closed early due to low accrual.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Won Kim, MD</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>877-827-3222</phone>
      <email>Won.Kim@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/NCT01695473
org study id: 115516
secondary id: NCI-2013-01830
nct id: NCT01695473
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II, study of BKM120 in patients with high-risk, localized prostate cancer.
      Eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy of the
      prostate to confirm high-risk disease and collect prostate tissue for analysis. Two weeks
      after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at
      this dose level orally once daily for 14 days prior to radical prostatectomy at University of
      California, San Francisco. Radical prostatectomy will be performed on the day of the last
      dose of BKM120 at day 14. No further drug will be tken after the radical prostatectomy.
This is a phase II, prospective, pharmacodynamic study of BKM120 in high-risk, localized
      prostate cancer. After informed consent and central pathology review of the core prostate
      biopsy, eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy
      of the prostate to confirm high-risk disease and collect tissue for molecular analysis. Two
      weeks after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given
      at this dose level orally once daily for 14 days prior to radical prostatectomy at University
      of California, San Francisco. Radical prostatectomy will be performed on the day of the last
      dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy.

      Up to 24 patients, or 21 evaluable patients, will be enrolled through the Department of
      Urology or Genitourinary Medical Oncology at the University of California, San Francisco for
      this pharmacodynamic study. Toxicity will be assessed during BKM120 administration, and will
      involve a clinic visit on Day 14 ± 2 (i.e. before surgery). Follow-up with safety evaluations
      will be at 90 ± 7 days post-operatively and involve a toxicity questionnaire, blood tests,
      and clinic visit. Toxicity will be monitored and reported using NCI Common Toxicity Criteria
      version 4.0 guidelines.

      A patient symptom diary will be distributed to each patient at baseline for symptom
      self-recording and BKM120 dose self-administration. In addition, a patient identifier card
      (wallet-sized) will be distributed to each patient after informed consent and registration.
      This information will contain the patient's age, study name and number, investigator and
      study coordinator contact information, and expected adverse events that may be present as a
      result of BKM120 administration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Decrease in Phosphorylated S6 Immunohistochemistry (ICH) From Baseline
time frame: Up to 3 months
description: Percentage of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration and defined as ≥ 60% decrease in phosphorylated S6 (pS6) from baseline by Immunohistochemistry (IHC).
measure: Percentage of Participants With Decrease in 4E-binding protein1 (p4EBP1) Protein Phosphorylation From Baseline
time frame: Up to 3 months
description: Percentage of men with downstream target inhibition of phosphatidylinositol 3-kinase (PI3K) in prostate tumor tissue as measured by 4E-binding protein1 (4EBP1) protein phosphorylation immunohistochemistry (IHC) using paired tumor biopsies from before and after drug administration and defined as >= 60% decline in p4EBP1 IHC
measure: Percentage of Participants With Decrease in AKT Protein From Baseline
time frame: Up to 3 months
description: Proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by Protein kinase B (pAKT) IHC determined by a >= 60% decline in pAKT IHC
measure: Number of Participants Displaying Activity of Short Term BKM120 Administration
time frame: 1 Day, immediately prior to surgery
description: Activity of short term BKM120 administration in prostate cancer was determined by measured PSA response immediately prior to radical prostatectomy
arm group label: Neoadjuvant BKM120
arm group type: Experimental
description: Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in operating room (OR) scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.
intervention type: Drug
intervention name: BKM120
description: Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.
arm group label: Neoadjuvant BKM120
other name: Buparlisib
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Won Kim, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Won Kim
investigator title: Prinicipal Investigator
mesh term: Prostatic Neoplasms
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was closed early due to low accrual.
point of contact: 