<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/NCT03042468</url>
  </required_header>
  <id_info>
    <org_study_id>1609017542</org_study_id>
    <secondary_id>PSMA-617</secondary_id>
    <nct_id>NCT03042468</nct_id>
  </id_info>
  <brief_title>Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC</brief_title>
  <official_title>Phase I/ll Dose-escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Weill Medical College of Cornell University</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>
      The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617&#xD;
      that can be given without severe side effects for advanced prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be&#xD;
      performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose&#xD;
      [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels&#xD;
      (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to&#xD;
      further assess safety and tolerability and to obtain a preliminary assessment of efficacy.&#xD;
      The study will enroll adult males 18 years of age or older with documented progressive&#xD;
      metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT)&#xD;
      of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended&#xD;
      phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive&#xD;
      the following study interventions:&#xD;
&#xD;
        1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart&#xD;
           (Visit 1 and 2)&#xD;
&#xD;
        2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks&#xD;
           with standard imaging Subjects will be on this study from screening to end of study (day&#xD;
           85).&#xD;
&#xD;
      The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until&#xD;
      death for survival assessment. Patients removed from study for unacceptable adverse events&#xD;
      will be followed until resolution or stabilization of the adverse event. All tests and&#xD;
      procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC&#xD;
      PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples&#xD;
      (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</primary_completion_date>
  <phase>Phase 1/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>Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617</measure>
    <time_frame>Assessed throughout the DLT period, up to 92 days after starting study drug.</time_frame>
    <description>Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617</measure>
    <time_frame>from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days</time_frame>
    <description>This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen</measure>
    <time_frame>Duration of Phase I, up to 47 months</time_frame>
    <description>Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617</measure>
    <time_frame>from baseline visit to short term follow up visit, approximately 6 months</time_frame>
    <description>Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications</measure>
    <time_frame>From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria</measure>
    <time_frame>Duration of time on study, from baseline to last follow up visit, up to 54 months</time_frame>
    <description>Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CTC Count Responders</measure>
    <time_frame>Duration of study, from screening to EOS visit, up to 12 weeks</time_frame>
    <description>Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617.&#xD;
All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Following Fractionated 177Lu-PSMA-617</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Participants That Experience an Adverse Event</measure>
    <time_frame>From screening to end of study visit, up to 54 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>All subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)&#xD;
68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>177Lu-PSMA-617</intervention_name>
    <description>177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>68Ga-PSMA-HBED-CC</intervention_name>
    <description>68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed adenocarcinoma of prostate&#xD;
&#xD;
          2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3&#xD;
             (PCWG3) criteria, which includes at least one of the following criteria:&#xD;
&#xD;
               -  PSA progression&#xD;
&#xD;
               -  Objective radiographic progression in soft tissue&#xD;
&#xD;
               -  New bone lesions&#xD;
&#xD;
          3. ECOG performance status of 0-2&#xD;
&#xD;
          4. Have serum testosterone &lt; 50 ng/dL. Subjects must continue primary androgen&#xD;
             deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone&#xD;
             orchiectomy.&#xD;
&#xD;
          5. Have previously been treated with at least one of the following:&#xD;
&#xD;
               -  Androgen receptor signaling inhibitor (such as enzalutamide)&#xD;
&#xD;
               -  CYP 17 inhibitor (such as abiraterone acetate)&#xD;
&#xD;
          6. Have previously received taxane chemotherapy, been determined to be ineligible for&#xD;
             taxane chemotherapy by their physician, or refused taxane chemotherapy.&#xD;
&#xD;
          7. Age &gt; 18 years&#xD;
&#xD;
          8. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count &gt;2,000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1&#xD;
                  month prior to registration)&#xD;
&#xD;
               -  Platelet count &gt;150,000 x 109/uL (independent of transfusion and/or growth&#xD;
                  factors within 3 months prior to randomization)&#xD;
&#xD;
               -  Serum creatinine &lt;1.5 x upper limit of normal (ULN) or calculated creatinine&#xD;
                  clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault&#xD;
&#xD;
               -  Serum total bilirubin &lt;1.5 x ULN (unless due to Gilbert's syndrome in which case&#xD;
                  direct bilirubin must be normal&#xD;
&#xD;
               -  Serum AST and ALT &lt;1.5 x ULN&#xD;
&#xD;
          9. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of investigational drugs or implantation of investigational medical device ≤4&#xD;
             weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study&#xD;
&#xD;
          2. Prior systemic beta-emitting bone-seeking radioisotopes&#xD;
&#xD;
          3. Brain metastases or leptomeningeal disease&#xD;
&#xD;
          4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry&#xD;
&#xD;
          5. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or&#xD;
             hematological organ systems which might preclude completion of this study or interfere&#xD;
             with determination of causality of any adverse effects experienced in this study&#xD;
&#xD;
          6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1&#xD;
&#xD;
          7. Patients on stable dose of bisphosphonates or denosumab, which have been started no&#xD;
             less than 4 weeks prior to treatment start, may continue on this medication, however&#xD;
             patients are not allowed to initiate bisphosphonate/Denosumab therapy during the&#xD;
             DLT-assessment period of the study.&#xD;
&#xD;
          8. Having partners of childbearing potential and not willing to use a method of birth&#xD;
             control deemed acceptable by the principle investigator and chairperson during the&#xD;
             study and for 1 month after last study drug administration&#xD;
&#xD;
          9. Currently active other malignancy other than non-melanoma skin cancer. Patients are&#xD;
             considered not to have &quot;currently active&quot; malignancy if they have completed any&#xD;
             necessary therapy and are considered by their physician to be at less than 30% risk of&#xD;
             relapse.&#xD;
&#xD;
         10. Known history of known myelodysplastic syndrome&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott Tagawa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tulane Cancer Center Clinic</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <results_first_submitted>September 30, 2022</results_first_submitted>
  <results_first_submitted_qc>November 16, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 13, 2022</results_first_posted>
  <last_update_submitted>November 16, 2022</last_update_submitted>
  <last_update_submitted_qc>November 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gallium 68 PSMA-11</mesh_term>
    <mesh_term>177Lu-PSMA-617</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 28, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/68/NCT03042468/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment took place at at Weill Cornell Medicine New York Presbyterian and Tulane Medical Center.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>177Lu-PSMA-617 Cohort 1</title>
          <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="P2">
          <title>177Lu-PSMA-617 Cohort 2</title>
          <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="P3">
          <title>177Lu-PSMA-617 Cohort 3</title>
          <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="P4">
          <title>177Lu-PSMA-617 Cohort 4</title>
          <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="P5">
          <title>177Lu-PSMA-617 Cohort 5</title>
          <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="P6">
          <title>Dose Expansion Cohort</title>
          <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>177Lu-PSMA-617 Cohort 1</title>
          <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="B2">
          <title>177Lu-PSMA-617 Cohort 2</title>
          <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="B3">
          <title>177Lu-PSMA-617 Cohort 3</title>
          <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="B4">
          <title>177Lu-PSMA-617 Cohort 4</title>
          <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="B5">
          <title>177Lu-PSMA-617 Cohort 5</title>
          <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="B6">
          <title>Dose Expansion Cohort</title>
          <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
        </group>
        <group group_id="B7">
          <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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="21"/>
            <count group_id="B7" value="50"/>
          </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="17"/>
                    <measurement group_id="B7" value="40"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="21"/>
                    <measurement group_id="B7" value="50"/>
                  </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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="19"/>
                    <measurement group_id="B7" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617</title>
        <description>Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.</description>
        <time_frame>Assessed throughout the DLT period, up to 92 days after starting study drug.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617</title>
          <description>Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.</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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617</title>
        <description>This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.</description>
        <time_frame>from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617</title>
          <description>This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.</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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen</title>
        <description>Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.</description>
        <time_frame>Duration of Phase I, up to 47 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Phase 1 Subjects</title>
            <description>177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)&#xD;
68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging&#xD;
177Lu-PSMA-617: 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)&#xD;
68Ga-PSMA-HBED-CC: 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging</description>
          </group>
        </group_list>
        <measure>
          <title>Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen</title>
          <description>Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.</description>
          <units>mci</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617</title>
        <description>Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.</description>
        <time_frame>from baseline visit to short term follow up visit, approximately 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617</title>
          <description>Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.</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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications</title>
        <time_frame>From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months</time_frame>
        <population>Only evaluable subjects were analyzed for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications</title>
          <population>Only evaluable subjects were analyzed for this measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="1"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria</title>
        <description>Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.</description>
        <time_frame>Duration of time on study, from baseline to last follow up visit, up to 54 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria</title>
          <description>Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95" lower_limit="42" upper_limit="118"/>
                    <measurement group_id="O2" value="147" lower_limit="14" upper_limit="429"/>
                    <measurement group_id="O3" value="119" lower_limit="14" upper_limit="357"/>
                    <measurement group_id="O4" value="188" lower_limit="83" upper_limit="449"/>
                    <measurement group_id="O5" value="99" lower_limit="13" upper_limit="265"/>
                    <measurement group_id="O6" value="176" lower_limit="14" upper_limit="1145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of CTC Count Responders</title>
        <description>Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617.&#xD;
All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.</description>
        <time_frame>Duration of study, from screening to EOS visit, up to 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>77Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of CTC Count Responders</title>
          <description>Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617.&#xD;
All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.</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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival Following Fractionated 177Lu-PSMA-617</title>
        <description>Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expasnion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival Following Fractionated 177Lu-PSMA-617</title>
          <description>Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="385" lower_limit="156" upper_limit="554"/>
                    <measurement group_id="O2" value="607" lower_limit="57" upper_limit="1471"/>
                    <measurement group_id="O3" value="368" lower_limit="51" upper_limit="763"/>
                    <measurement group_id="O4" value="743" lower_limit="248" upper_limit="1595"/>
                    <measurement group_id="O5" value="409" lower_limit="84" upper_limit="751"/>
                    <measurement group_id="O6" value="478" lower_limit="110" upper_limit="1617"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants That Experience an Adverse Event</title>
        <time_frame>From screening to end of study visit, up to 54 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>177Lu-PSMA-617 Cohort 1</title>
            <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O2">
            <title>177Lu-PSMA-617 Cohort 2</title>
            <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O3">
            <title>177Lu-PSMA-617 Cohort 3</title>
            <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O4">
            <title>177Lu-PSMA-617 Cohort 4</title>
            <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O5">
            <title>177Lu-PSMA-617 Cohort 5</title>
            <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
          </group>
          <group group_id="O6">
            <title>Dose Expansion Cohort</title>
            <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants That Experience an Adverse Event</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events collected during the duration of the study, from start of study to end of study, up to 5 years.</time_frame>
      <desc>Patients who passed away during the follow up period were also included.</desc>
      <group_list>
        <group group_id="E1">
          <title>177Lu-PSMA-617 Cohort 1</title>
          <description>Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="E2">
          <title>177Lu-PSMA-617 Cohort 2</title>
          <description>Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="E3">
          <title>177Lu-PSMA-617 Cohort 3</title>
          <description>Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="E4">
          <title>177Lu-PSMA-617 Cohort 4</title>
          <description>Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="E5">
          <title>177Lu-PSMA-617 Cohort 5</title>
          <description>Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment</description>
        </group>
        <group group_id="E6">
          <title>Dose Expansion Cohort</title>
          <description>Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment.</description>
        </group>
      </group_list>
      <serious_events>
        <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, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="19" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bacteremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death due to disease progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Lower Extremity Weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="21" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" events="17" subjects_affected="17" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>AST increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>High Creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>ALP increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>ALT increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoalbuminenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Leukopenia (white blood cell count decreased)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dry eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Xerostemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" events="14" subjects_affected="14" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" events="19" subjects_affected="19" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" events="19" subjects_affected="19" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="14" subjects_affected="14" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bells palsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Death due to progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysguesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Facial trauma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nocturia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgias</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Muscle weakness LL</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Peritendinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr. Scott Tagawa</name_or_title>
      <organization>Weill Cornell Medicine</organization>
      <phone>646-962-2027</phone>
      <email>stt2007@med.cornell.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/NCT03042468
org study id: 1609017542
secondary id: PSMA-617
nct id: NCT03042468
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617
      that can be given without severe side effects for advanced prostate cancer.
Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be
      performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose
      [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels
      (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to
      further assess safety and tolerability and to obtain a preliminary assessment of efficacy.
      The study will enroll adult males 18 years of age or older with documented progressive
      metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT)
      of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended
      phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive
      the following study interventions:

        1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart
           (Visit 1 and 2)

        2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks
           with standard imaging Subjects will be on this study from screening to end of study (day
           85).

      The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until
      death for survival assessment. Patients removed from study for unacceptable adverse events
      will be followed until resolution or stabilization of the adverse event. All tests and
      procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC
      PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples
      (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617
time frame: Assessed throughout the DLT period, up to 92 days after starting study drug.
description: Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.
measure: Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617
time frame: from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days
description: This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.
measure: Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen
time frame: Duration of Phase I, up to 47 months
description: Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.
measure: The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617
time frame: from baseline visit to short term follow up visit, approximately 6 months
description: Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.
measure: Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications
time frame: From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months
measure: Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria
time frame: Duration of time on study, from baseline to last follow up visit, up to 54 months
description: Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.
measure: Number of CTC Count Responders
time frame: Duration of study, from screening to EOS visit, up to 12 weeks
description: Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617.
All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.
measure: Overall Survival Following Fractionated 177Lu-PSMA-617
time frame: Up to 5 years
description: Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.
measure: Count of Participants That Experience an Adverse Event
time frame: From screening to end of study visit, up to 54 months
arm group label: All subjects
arm group type: Experimental
description: 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging
intervention type: Drug
intervention name: 177Lu-PSMA-617
description: 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
arm group label: All subjects
intervention type: Drug
intervention name: 68Ga-PSMA-HBED-CC
description: 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging
arm group label: All subjects
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Scott Tagawa, MD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Gallium 68 PSMA-11
mesh term: 177Lu-PSMA-617
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 