<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/NCT01703065</url>
  </required_header>
  <id_info>
    <org_study_id>7819</org_study_id>
    <secondary_id>NCI-2012-01898</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT01703065</nct_id>
  </id_info>
  <brief_title>Cabozantinib in Men With Castration-Resistant Prostate Cancer</brief_title>
  <official_title>A Pilot Study of the Effects of Cabozantinib (XL184) on Bone Turnover and the Microenvironment in Men With Non-Metastatic and Metastatic Castration-Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Prostate Cancer Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies cabozantinib in treating men with castration-resistant&#xD;
      prostate cancer. Cabozantinib may stop the growth of tumor cells by blocking some of the&#xD;
      enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Outcome Measure:&#xD;
&#xD;
        1. Change in urinary N-telopeptide (uNTX) from baseline to after 6 weeks of treatment with&#xD;
           cabozantinib in men with non-metastatic CRPC.&#xD;
&#xD;
           Secondary Outcome Measures:&#xD;
&#xD;
        2. Changes in serum markers of bone metabolism from baseline to after 6 weeks of treatment&#xD;
           with cabozantinib. Markers of bone metabolism in blood include bone specific alkaline&#xD;
           phosphatase, alkaline phosphatase, LDH.&#xD;
&#xD;
        3. Changes in biomarker expression in bone biopsy samples. To include MET, AKT, FASN and&#xD;
           VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and&#xD;
           prostate cancer cells. Will also include changes in markers of apoptosis, proliferation,&#xD;
           and angiogenesis.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive cabozantinib orally (PO) once daily (QD) in the absence of disease&#xD;
      progression or unacceptable toxicity. After completion of study treatment, patients are&#xD;
      followed up for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Closed 2017 for low accrual. Last data for primary outcome on 02Feb2015.&#xD;
  </why_stopped>
  <start_date type="Actual">June 18, 2013</start_date>
  <completion_date type="Actual">September 18, 2015</completion_date>
  <primary_completion_date type="Actual">February 2, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Two separate patient population arms (metastatic CRPC and non-metastatic CRPC) but both populations are given the same interventional treatment and the same safety assessments.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Treatment is open label and non-randomized. Split in to two patient populations - metastatic CRPC and non-metastatic CRPC.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Urinary N-telopeptide (uNTX) as a Marker of Bone Metabolism in Non-metastatic Patients</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Median percent change in Urinary N-Telopeptide from baseline compared to after 6 weeks of treatment with Cabozantinib in patients with non-metastatic prostate cancer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Bone Specific Alkaline Phosphatase as a Marker of Bone Metabolism</measure>
    <time_frame>Baseline and at 6 weeks</time_frame>
    <description>Median percent change in Bone Specific Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Alkaline Phosphatase as a Marker of Bone Metabolism</measure>
    <time_frame>Baseline, 6 weeks</time_frame>
    <description>Median percent change in Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Lactic Acid Dehydrogenase (LDH) as a Marker of Bone Metabolism</measure>
    <time_frame>Baseline and at 6 weeks</time_frame>
    <description>Median percent change in Lactic Acid Dehydrogenase (LDH) from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Biomarker Expression in Bone Biopsy Samples</measure>
    <time_frame>Baseline and at 6 weeks</time_frame>
    <description>To include MET, AKT, FASN and VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and prostate cancer cells. Will also include changes in markers of apoptosis, proliferation, and angiogenesis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Adenocarcinoma of the Prostate</condition>
  <condition>Castration-resistant Prostate Cancer</condition>
  <condition>Recurrent Prostate Cancer</condition>
  <condition>Stage III Prostate Cancer</condition>
  <condition>Stage IV Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Cabozantinib in metastatic CRPC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cabozantinib in non-metastatic CRPC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib</intervention_name>
    <description>Given orally once a day</description>
    <arm_group_label>Cabozantinib in metastatic CRPC</arm_group_label>
    <arm_group_label>Cabozantinib in non-metastatic CRPC</arm_group_label>
    <other_name>BMS-907351</other_name>
    <other_name>Cometriq</other_name>
    <other_name>XL184</other_name>
    <other_name>cabozantinib-s-malate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          1. The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may have&#xD;
             undergone prior surgery and/or radiation.&#xD;
&#xD;
          2. The subject must currently have castration resistant prostate cancer defined as 2&#xD;
             serial rising PSAs with a castrate level of testosterone (&lt;50 ng/dL).&#xD;
&#xD;
          3. A subject with non-metastatic CRPC may not have received prior chemotherapy unless in&#xD;
             the neoadjuvant or adjuvant setting &gt; 24 months ago and may not have received prior&#xD;
             zoledronic acid or denosumab.&#xD;
&#xD;
          4. A subject with metastatic CRPC must have bone metastases accessible for biopsy by CT&#xD;
             guidance.&#xD;
&#xD;
          5. The subject must be willing to undergo sequential biopsy of bone or bone metastases.&#xD;
&#xD;
          6. Subjects must have discontinued additional hormonal (eg bicalutamide, abiraterone,&#xD;
             estrogen) therapy prior to the first dose of cabozantinib. No antiandrogen withdrawal&#xD;
             period is required.&#xD;
&#xD;
          7. Subjects previously treated on another investigational agent must have a 2-week or&#xD;
             more washout before starting cabozantinib, depending on the agent, toxicity profile,&#xD;
             and half-life. However, such patients may begin tetracycline dosing after consent is&#xD;
             signed.&#xD;
&#xD;
          8. Subjects who are currently on GnRH agonists or antagonist therapy must continue&#xD;
             androgen suppression.&#xD;
&#xD;
          9. The subject is ≥18 years old on day of consent.&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.&#xD;
&#xD;
         11. Organ and marrow function as follows:&#xD;
&#xD;
               1. ANC ≥1500/mm3 without colony stimulating factor support.&#xD;
&#xD;
               2. Platelets ≥100,000/mm3.&#xD;
&#xD;
               3. Hemoglobin ≥9 g/dL.&#xD;
&#xD;
               4. Total bilirubin ≤1.5 x the upper limit of normal (ULN). For subjects with known&#xD;
                  Gilbert's disease, bilirubin≤3.0 mg/dL.&#xD;
&#xD;
               5. Serum albumin ≥2.8g/dL.&#xD;
&#xD;
               6. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance &gt;50 mL/min. The&#xD;
                  Cockcroft and Gault equation should be used: Male: CrCl (mL/min) = (140 - age) ×&#xD;
                  wt (kg) / (serum creatinine × 72).&#xD;
&#xD;
               7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN.&#xD;
&#xD;
               8. Lipase &lt;2.0 × ULN and no radiologic or clinical evidence of pancreatitis.&#xD;
&#xD;
               9. Serum testosterone level &lt;50 ng/dL.&#xD;
&#xD;
              10. Urine protein/creatinine (UPC) ratio ≤1.0 unless the patient has a neobladder.&#xD;
&#xD;
              11. Serum phosphorus, magnesium, calcium and potassium ≥ lower limit of normal (LLN).&#xD;
&#xD;
         12. The subject is capable of understanding and complying with the protocol requirements&#xD;
             and has signed the informed consent document.&#xD;
&#xD;
         13. Sexually active subjects and their partners must agree to use medically accepted&#xD;
             barrier methods of contraception (eg, male or female condom) during the course of the&#xD;
             study and for 4 months after the last dose of study drug(s), even if oral&#xD;
             contraceptives are also used. All subjects of reproductive potential must agree to use&#xD;
             both a barrier method and a second method of birth control during the course of the&#xD;
             study.&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          1. The subject has received cytotoxic chemotherapy (including investigational cytotoxic&#xD;
             chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or&#xD;
             nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment.&#xD;
&#xD;
          2. Prior treatment with cabozantinib and other met inhibitors.&#xD;
&#xD;
          3. Prior treatment with a small molecule kinase inhibitor or a hormonal therapy&#xD;
             (including investigational kinase inhibitors or hormones) within 14 days or five&#xD;
             half-lives of the compound or active metabolites, whichever is longer, or before the&#xD;
             first dose of study treatment.&#xD;
&#xD;
          4. The subject has received radiation therapy:&#xD;
&#xD;
               1. to the thoracic cavity or gastrointestinal tract within 3 months of the first&#xD;
                  dose of study treatment.&#xD;
&#xD;
               2. to bone or brain metastasis within 14 days of the first dose of study treatment.&#xD;
&#xD;
               3. to any other site(s) within 28 days of the first dose of study treatment.&#xD;
&#xD;
          5. The subject has received radionuclide treatment within 6 weeks of the first dose of&#xD;
             study treatment.&#xD;
&#xD;
          6. The subject has received any other type of investigational agent within 28 days before&#xD;
             the first dose of study treatment.&#xD;
&#xD;
          7. The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all&#xD;
             prior therapies except alopecia and other non-clinically significant AEs.&#xD;
&#xD;
          8. The subject has a primary brain tumor.&#xD;
&#xD;
          9. The subject has active brain metastases or epidural disease (Note: Subjects with brain&#xD;
             metastases previously treated with whole brain radiation or radiosurgery or subjects&#xD;
             with epidural disease previously treated with radiation or surgery who are&#xD;
             asymptomatic and do not require steroid treatment for at least 2 weeks before starting&#xD;
             study treatment are eligible. Neurosurgical resection of brain metastases or brain&#xD;
             biopsy is permitted if completed at least 3 months before starting study treatment.&#xD;
             Baseline brain scans are not required to confirm eligibility.)&#xD;
&#xD;
         10. The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial&#xD;
             thromboplastin time (PTT) test results at screening ≥ 1.3 x the laboratory ULN.&#xD;
&#xD;
         11. The subject requires concomitant treatment, in therapeutic doses, with anticoagulants&#xD;
             such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa&#xD;
             inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day),&#xD;
             low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH)&#xD;
             are permitted.&#xD;
&#xD;
         12. The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g.,&#xD;
             dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,&#xD;
             phenobarbital, and St. John's Wort). Because the lists of these agents are constantly&#xD;
             changing, it is important to regularly consult a frequently-updated list such as&#xD;
             http://medicine.iupui.edu/clinpharm/ddis/table.asp; medical reference texts such as&#xD;
             the Physicians' Desk Reference may also provide this information. As part of the&#xD;
             enrollment/informed consent procedures, the patient will be counseled on the risk of&#xD;
             interactions with other agents, and what to do if new medications need to be&#xD;
             prescribed or if the patient is considering a new over-the-counter medicine or herbal&#xD;
             product.&#xD;
&#xD;
         13. The subject has experienced any of the following:&#xD;
&#xD;
               1. clinically-significant gastrointestinal bleeding within 6 months before the first&#xD;
                  dose of study treatment.&#xD;
&#xD;
               2. hemoptysis of ≥0.5 teaspoon (2.5 mL) of red blood within 3 months before the&#xD;
                  first dose of study treatment.&#xD;
&#xD;
               3. any other signs indicative of pulmonary hemorrhage within 3 months before the&#xD;
                  first dose of study treatment.&#xD;
&#xD;
         14. The subject has radiographic evidence of cavitating pulmonary lesion(s).&#xD;
&#xD;
         15. The subject has tumor in contact with, invading or encasing major blood vessels.&#xD;
&#xD;
         16. The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or&#xD;
             large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor&#xD;
             within 28 days before the first dose of cabozantinib.&#xD;
&#xD;
         17. The subject has uncontrolled, significant intercurrent or recent illness including,&#xD;
             but not limited to, the following conditions:&#xD;
&#xD;
             a. Cardiovascular disorders including: i. Congestive heart failure (CHF): New York&#xD;
             Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of&#xD;
             screening.&#xD;
&#xD;
             ii. Concurrent uncontrolled hypertension defined as sustained BP &gt; 140 mm Hg systolic,&#xD;
             or &gt; 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days&#xD;
             before the first dose of study treatment.&#xD;
&#xD;
             iii. Any history of congenital long QT syndrome. iv. Any of the following within 6&#xD;
             months before the first dose of study treatment:&#xD;
&#xD;
               -  unstable angina pectoris&#xD;
&#xD;
               -  clinically-significant cardiac arrhythmias&#xD;
&#xD;
               -  stroke (including TIA, or other ischemic event)&#xD;
&#xD;
               -  myocardial infarction&#xD;
&#xD;
               -  thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a&#xD;
                  venous filter (e.g. vena cava filter) are not eligible for this study) b.&#xD;
                  Gastrointestinal disorders particularly those associated with a high risk of&#xD;
                  perforation or fistula formation including: i. Any of the following within 28&#xD;
                  days before the first dose of study treatment:&#xD;
&#xD;
               -  intra-abdominal tumor/metastases invading GI mucosa&#xD;
&#xD;
               -  active peptic ulcer disease&#xD;
&#xD;
               -  inflammatory bowel disease (including ulcerative colitis and Crohn's disease),&#xD;
                  diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis&#xD;
&#xD;
               -  malabsorption syndrome ii. Any of the following within 6 months before the first&#xD;
                  dose of study treatment:&#xD;
&#xD;
               -  abdominal fistula&#xD;
&#xD;
               -  gastrointestinal perforation&#xD;
&#xD;
               -  bowel obstruction or gastric outlet obstruction&#xD;
&#xD;
               -  intra-abdominal abscess. Note: Complete resolution of an intraabdominal abscess&#xD;
                  must be confirmed prior to initiating treatment with cabozantinib even if the&#xD;
                  abscess occurred more that 6 months before the first dose of study treatment.&#xD;
&#xD;
                  c. Other disorders associated with a high risk of fistula formation including PEG&#xD;
                  tube placement within 3 months before the first dose of study therapy.&#xD;
&#xD;
                  d. Other clinically significant disorders such as: i. active infection requiring&#xD;
                  systemic treatment within 28 days before the first dose of study treatment ii.&#xD;
                  serious non-healing wound/ulcer/bone fracture within 28 days before the first&#xD;
                  dose of study treatment iii. history of organ transplant iv. concurrent&#xD;
                  uncompensated hypothyroidism or thyroid dysfunction within 7 days before the&#xD;
                  first dose of study treatment v. history of major surgery as follows:&#xD;
&#xD;
               -  Major surgery within 3 months of the first dose of cabozantinib if there were no&#xD;
                  wound healing complications or within 6 months of the first dose of cabozantinib&#xD;
                  if there were wound complications&#xD;
&#xD;
               -  Minor surgery within 1 months of the first dose of cabozantinib if there were no&#xD;
                  wound healing complications or within 3 months of the first dose of cabozantinib&#xD;
                  if there were wound complications In addition, complete wound healing from prior&#xD;
                  surgery must be confirmed at least 28 days before the first dose of cabozantinib&#xD;
                  irrespective of the time from surgery&#xD;
&#xD;
         18. The subject is unable to swallow tablets.&#xD;
&#xD;
         19. The subject has a corrected QT interval calculated by the Fridericia formula (QTcF)&#xD;
             &gt;500 ms within 28 days before Day 1 of Cycle 1. Note: if initial QTcF is found to be &gt;&#xD;
             500 ms, two additional EKGs separated by at least 3 minutes should be performed. If&#xD;
             the average of these three consecutive results for QTcF is ≤500 ms, the subject meets&#xD;
             eligibility in this regard.&#xD;
&#xD;
         20. The subject has a previously identified allergy or hypersensitivity to components of&#xD;
             the study treatment formulation.&#xD;
&#xD;
         21. The subject is unable or unwilling to abide by the study protocol or cooperate fully&#xD;
             with the investigator or designee.&#xD;
&#xD;
         22. For disease specific studies: The subject has had evidence within 2 years of the start&#xD;
             of study treatment of another malignancy which required systemic treatment.&#xD;
&#xD;
         23. The subject has a known allergy to tetracycline.&#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>Celestia S Higano, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance/University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 5, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <results_first_submitted>August 3, 2018</results_first_submitted>
  <results_first_submitted_qc>November 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 4, 2018</results_first_posted>
  <disposition_first_submitted>October 16, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>November 25, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 5, 2017</disposition_first_posted>
  <last_update_submitted>November 6, 2018</last_update_submitted>
  <last_update_submitted_qc>November 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Celestia Higano</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Prostate cancer</keyword>
  <keyword>Bone metastases</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>
    <ipd_description>We do not plan to make individual participant data (IPD) available to other researchers.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cabozantinib in Metastatic CRPC</title>
          <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
        <group group_id="P2">
          <title>Cabozantinib in Non-metastatic CRPC</title>
          <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>0 nmCRPC patients enrolled, so 0 nmCRPC patients analyzed.</population>
      <group_list>
        <group group_id="B1">
          <title>Cabozantinib in Metastatic CRPC</title>
          <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
        <group group_id="B2">
          <title>Cabozantinib in Non-metastatic CRPC</title>
          <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="9"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B3" 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 group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </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="9"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Urinary N-telopeptide (uNTX) as a Marker of Bone Metabolism in Non-metastatic Patients</title>
        <description>Median percent change in Urinary N-Telopeptide from baseline compared to after 6 weeks of treatment with Cabozantinib in patients with non-metastatic prostate cancer.</description>
        <time_frame>Baseline and 6 weeks</time_frame>
        <population>Of 9 total patients enrolled, 0 had non-metastatic CRPC, therefore this outcome was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib in Non-metastatic CRPC</title>
            <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Urinary N-telopeptide (uNTX) as a Marker of Bone Metabolism in Non-metastatic Patients</title>
          <description>Median percent change in Urinary N-Telopeptide from baseline compared to after 6 weeks of treatment with Cabozantinib in patients with non-metastatic prostate cancer.</description>
          <population>Of 9 total patients enrolled, 0 had non-metastatic CRPC, therefore this outcome was not analyzed.</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>Change in Bone Specific Alkaline Phosphatase as a Marker of Bone Metabolism</title>
        <description>Median percent change in Bone Specific Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
        <time_frame>Baseline and at 6 weeks</time_frame>
        <population>Bone Specific Alkaline Phosphate was analyzed in blood samples from 8 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 1 participant did not provide a 6 week sample, and was therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib in Metastatic CRPC</title>
            <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
          <group group_id="O2">
            <title>Cabozantinib in Non-metastatic CRPC</title>
            <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Bone Specific Alkaline Phosphatase as a Marker of Bone Metabolism</title>
          <description>Median percent change in Bone Specific Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
          <population>Bone Specific Alkaline Phosphate was analyzed in blood samples from 8 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 1 participant did not provide a 6 week sample, and was therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
          <units>percent change</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="42.83" lower_limit="-45.10" upper_limit="269.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alkaline Phosphatase as a Marker of Bone Metabolism</title>
        <description>Median percent change in Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
        <time_frame>Baseline, 6 weeks</time_frame>
        <population>Alkaline Phosphatase was analyzed in blood samples from 7 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 2 participants did not provide a 6 week sample and were therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib in Metastatic CRPC</title>
            <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
          <group group_id="O2">
            <title>Cabozantinib in Non-metastatic CRPC</title>
            <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alkaline Phosphatase as a Marker of Bone Metabolism</title>
          <description>Median percent change in Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
          <population>Alkaline Phosphatase was analyzed in blood samples from 7 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 2 participants did not provide a 6 week sample and were therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
          <units>percent change</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.88" lower_limit="-28.92" upper_limit="272.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Lactic Acid Dehydrogenase (LDH) as a Marker of Bone Metabolism</title>
        <description>Median percent change in Lactic Acid Dehydrogenase (LDH) from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
        <time_frame>Baseline and at 6 weeks</time_frame>
        <population>Lactic Acid Dehydrogenase (LDH) was analyzed in blood samples from 8 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 1 participant did not provide a 6 week sample and was therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib in Metastatic CRPC</title>
            <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
          <group group_id="O2">
            <title>Cabozantinib in Non-metastatic CRPC</title>
            <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Lactic Acid Dehydrogenase (LDH) as a Marker of Bone Metabolism</title>
          <description>Median percent change in Lactic Acid Dehydrogenase (LDH) from baseline compared to after 6 weeks of treatment with Cabozantinib.</description>
          <population>Lactic Acid Dehydrogenase (LDH) was analyzed in blood samples from 8 patients with metastatic CRPC at baseline and following 6 weeks of treatment. 1 participant did not provide a 6 week sample and was therefore excluded from this analysis. 0 participants were enrolled in the non-metastatic CRPC arm.</population>
          <units>percent change</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="65.27" lower_limit="12.59" upper_limit="120.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Biomarker Expression in Bone Biopsy Samples</title>
        <description>To include MET, AKT, FASN and VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and prostate cancer cells. Will also include changes in markers of apoptosis, proliferation, and angiogenesis.</description>
        <time_frame>Baseline and at 6 weeks</time_frame>
        <population>No nmCRCP patients enrolled, so no bone samples analyzed for this cohort. The purpose of biopsies in mCRPC cohort was to compare with those in nmCRPC cohort. Since no data to compare to, bone biopsy samples obtained were not analyzed. Only 1 patient with day 43 biopsy had specimen collected in both formalin and ethanol at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib in Metastatic CRPC</title>
            <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
          <group group_id="O2">
            <title>Cabozantinib in Non-metastatic CRPC</title>
            <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Biomarker Expression in Bone Biopsy Samples</title>
          <description>To include MET, AKT, FASN and VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and prostate cancer cells. Will also include changes in markers of apoptosis, proliferation, and angiogenesis.</description>
          <population>No nmCRCP patients enrolled, so no bone samples analyzed for this cohort. The purpose of biopsies in mCRPC cohort was to compare with those in nmCRPC cohort. Since no data to compare to, bone biopsy samples obtained were not analyzed. Only 1 patient with day 43 biopsy had specimen collected in both formalin and ethanol at baseline.</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_list>

    <reported_events>
      <time_frame>Adverse event data were collected for each patient from first dose of study treatment through 30 days after the last dose of study treatment.</time_frame>
      <desc>Adverse events were recorded for patients in the metastatic arm. There were no patients enrolled in the non-metastatic arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cabozantinib in Metastatic CRPC</title>
          <description>Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
        <group group_id="E2">
          <title>Cabozantinib in Non-metastatic CRPC</title>
          <description>Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.&#xD;
Cabozantinib: Given orally once a day</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Refractory MultiFocal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>increased triglycerides</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated TSH</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Mouth sore</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Laringeal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Heart burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Loose stools</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>GERD</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Mucositis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dry heaving</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chest pain, non-cardiac</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sacral pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hemorrhoidal bleeding</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hand-Foot syndrome</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Runny nose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Body aches</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Right upper arm bruising</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pharingitis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>ALT increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>AST increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Left hip pain</sub_title>
                <description>Pain from biopsy</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Low back pain increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Right shoulder pain - muscle</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Polyartralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Right hip pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bilateral leg pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pelvis pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Right scapular pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Cervical and lumbar spine pain</sub_title>
                <description>post-traumatic</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Left heel pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Muscle cramp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bilateral knee pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Right hand neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dark colored urine</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Seborrheic dermatitis, right ear</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash, right groin</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyperpigmented papules</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Telangiectasia cheeks</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Enrollment goal was 34 evaluable patients. A total of 9 patients were consented and enrolled, 0 non-metastatic and 9 metastatic. Given that fewer patients enrolled than expected, some endpoints are not-evaluable or inconclusive.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Celestia Higano, MD</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-606-1152</phone>
      <email>thigano@u.washington.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/NCT01703065
org study id: 7819
secondary id: NCI-2012-01898
secondary id: P30CA015704
nct id: NCT01703065
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
This pilot clinical trial studies cabozantinib in treating men with castration-resistant
      prostate cancer. Cabozantinib may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth.
Primary Outcome Measure:

        1. Change in urinary N-telopeptide (uNTX) from baseline to after 6 weeks of treatment with
           cabozantinib in men with non-metastatic CRPC.

           Secondary Outcome Measures:

        2. Changes in serum markers of bone metabolism from baseline to after 6 weeks of treatment
           with cabozantinib. Markers of bone metabolism in blood include bone specific alkaline
           phosphatase, alkaline phosphatase, LDH.

        3. Changes in biomarker expression in bone biopsy samples. To include MET, AKT, FASN and
           VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and
           prostate cancer cells. Will also include changes in markers of apoptosis, proliferation,
           and angiogenesis.

      OUTLINE:

      Patients receive cabozantinib orally (PO) once daily (QD) in the absence of disease
      progression or unacceptable toxicity. After completion of study treatment, patients are
      followed up for 4 weeks.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Two separate patient population arms (metastatic CRPC and non-metastatic CRPC) but both populations are given the same interventional treatment and the same safety assessments.
primary purpose: Treatment
masking: None (Open Label)
masking description: Treatment is open label and non-randomized. Split in to two patient populations - metastatic CRPC and non-metastatic CRPC.
measure: Change in Urinary N-telopeptide (uNTX) as a Marker of Bone Metabolism in Non-metastatic Patients
time frame: Baseline and 6 weeks
description: Median percent change in Urinary N-Telopeptide from baseline compared to after 6 weeks of treatment with Cabozantinib in patients with non-metastatic prostate cancer.
measure: Change in Bone Specific Alkaline Phosphatase as a Marker of Bone Metabolism
time frame: Baseline and at 6 weeks
description: Median percent change in Bone Specific Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.
measure: Change in Alkaline Phosphatase as a Marker of Bone Metabolism
time frame: Baseline, 6 weeks
description: Median percent change in Alkaline Phosphatase from baseline compared to after 6 weeks of treatment with Cabozantinib.
measure: Change in Lactic Acid Dehydrogenase (LDH) as a Marker of Bone Metabolism
time frame: Baseline and at 6 weeks
description: Median percent change in Lactic Acid Dehydrogenase (LDH) from baseline compared to after 6 weeks of treatment with Cabozantinib.
measure: Changes in Biomarker Expression in Bone Biopsy Samples
time frame: Baseline and at 6 weeks
description: To include MET, AKT, FASN and VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and prostate cancer cells. Will also include changes in markers of apoptosis, proliferation, and angiogenesis.
arm group label: Cabozantinib in metastatic CRPC
arm group type: Experimental
description: Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.
arm group label: Cabozantinib in non-metastatic CRPC
arm group type: Experimental
description: Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cabozantinib
description: Given orally once a day
arm group label: Cabozantinib in metastatic CRPC
arm group label: Cabozantinib in non-metastatic CRPC
other name: BMS-907351
other name: Cometriq
other name: XL184
other name: cabozantinib-s-malate
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Celestia S Higano, MD
role: Principal Investigator
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Celestia Higano
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms
sharing ipd: No
ipd description: We do not plan to make individual participant data (IPD) available to other researchers.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Enrollment goal was 34 evaluable patients. A total of 9 patients were consented and enrolled, 0 non-metastatic and 9 metastatic. Given that fewer patients enrolled than expected, some endpoints are not-evaluable or inconclusive.
point of contact: 