<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/NCT04430192</url>
  </required_header>
  <id_info>
    <org_study_id>19_245</org_study_id>
    <nct_id>NCT04430192</nct_id>
  </id_info>
  <brief_title>Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy</brief_title>
  <acronym>LuTectomy</acronym>
  <official_title>Study of the Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Radionuclide Therapy Prior to Radical Prostatectomy in Men With High-risk Localised Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Movember Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical Research Future Fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Endocyte</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>E.J. Whitten Foundation Prostate Cancer Research Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peter MacCallum Cancer Centre, Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial will evaluate the dosimetry, efficacy and toxicity of Lu-PSMA in men with&#xD;
      high PSMA-expressing high-risk localized or locoregional advanced prostate cancer (HRCaP)&#xD;
      undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open label, phase I/II non-randomised clinical trial will evaluate the dosimetry,&#xD;
      efficacy and toxicity of Lu-PSMA in men with high PSMA-expressing high-risk localized or&#xD;
      locoregional advanced prostate cancer (HRCaP) undergoing radical prostatectomy (RP) and&#xD;
      pelvic lymph node dissection (PLND). Patients will receive one or two cycles of 177Lu-PSMA&#xD;
      followed by surgery. The primary objective is to determine the radiation absorbed dose in the&#xD;
      prostate and involved lymph nodes. Secondary objectives include evaluating imaging response&#xD;
      to therapy using PSMA-PET, biochemical response, pathological response, adverse effects of&#xD;
      Lu-PSMA and surgical safety, and health-related Quality of Life (QoL).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Actual">December 22, 2022</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>To determine the radiation absorbed dose in the prostate and involved lymph nodes following one or two administrations of Lu-PSMA in men with HRCaP prior to radical prostatectomy</measure>
    <time_frame>Determined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA</time_frame>
    <description>Establishing the absorbed radiation dose in the prostate and involved lymph nodes (Gy)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the imaging response to therapy using PSMA-PET</measure>
    <time_frame>6 weeks following final administration of Lu-PSMA</time_frame>
    <description>PSMA PET response to therapy (complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the biochemical response to therapy</measure>
    <time_frame>6 weeks following final administration of Lu-PSMA</time_frame>
    <description>PSA response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate pathologic response in the prostate following prostatectomy</measure>
    <time_frame>After prostatectomy, approximately 6 weeks from final Lu-PSMA administration</time_frame>
    <description>Pathological response (complete response, minimal residual disease)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate toxicity of Lu-PSMA</measure>
    <time_frame>Until 8 weeks after prostatectomy</time_frame>
    <description>Assessment of toxicity of Lu-PSMA using Common Terminology Criteria for Adverse Events (CTCAE) v5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the surgical safety of prostatectomy following Lu-PSMA</measure>
    <time_frame>Until 8 weeks after prostatectomy</time_frame>
    <description>Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate overall health-related Quality of Life (QoL)</measure>
    <time_frame>baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years</time_frame>
    <description>QoL indices will be scored using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate prostate cancer health-related Quality of Life (QoL)</measure>
    <time_frame>baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years</time_frame>
    <description>QoL indices will be scored using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate patient function and bother after prostatectomy</measure>
    <time_frame>baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years</time_frame>
    <description>Indices will be scored using the Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To determine the time to biochemical recurrence (BCR) [PSA&gt;0.2 ng/mL post-RP]</measure>
    <time_frame>To be determined as it is an exploratory endpoint up to 3 years</time_frame>
    <description>Biochemical recurrence (BCR) will be measured from the time of surgery to the first rise of the PSA to ≥0.2 ng/mL</description>
  </other_outcome>
  <other_outcome>
    <measure>To determine the relationship between PSMA PET imaging parameters and absorbed dose</measure>
    <time_frame>baseline PSMA PET within 45 days of Lu-PSMA administration</time_frame>
    <description>Determination of the relationship between screening PSMA PET imaging parameters including molecular tumour volume parameters and absorbed dose in the prostate and involved lymph nodes</description>
  </other_outcome>
  <other_outcome>
    <measure>To identify tissue and blood and serum biomarkers associated with clinical outcomes</measure>
    <time_frame>To be determined as it is an exploratory endpoint up to 3 years</time_frame>
    <description>Determination of relevant predictive biomarkers associated with treatment outcomes and response</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>177Lu-PSMA-617 followed by prostatectomy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>177Lu-PSMA-617 followed by prostatectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>177Lu-PSMA-617</intervention_name>
    <description>Patients 1-10 will be given 5GBq of 177Lu-PSMA. Patients 11-20 will be given 2 cycles of 5GBq of 177Lu-PSMA, separated by 6 weeks.</description>
    <arm_group_label>177Lu-PSMA-617 followed by prostatectomy</arm_group_label>
    <other_name>177Lu-PSMA</other_name>
    <other_name>[177Lu]Lu-PSMA-617</other_name>
    <other_name>Lu-PSMA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has provided written informed consent.&#xD;
&#xD;
          -  Male patient aged 18 or over at the time of screening&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the prostate, in a patient scheduled for RP&#xD;
             and PLND with curative intent&#xD;
&#xD;
          -  High or high-intermediate risk localised or locoregional prostate cancer (HRCaP) by&#xD;
             European Association of Urology (EAU) criteria, including any of the following:&#xD;
&#xD;
               -  PSA &gt; 20 ng/mL&#xD;
&#xD;
               -  ISUP grade group 3-5&#xD;
&#xD;
               -  Clinical T-stage by digital rectal examination (DRE) of T2c or higher&#xD;
&#xD;
               -  N1 disease (involvement of lymph nodes at or below the bifurcation of the common&#xD;
                  iliac arteries)&#xD;
&#xD;
               -  defined radiologically (CT/ MRI, or PSMA PET).&#xD;
&#xD;
          -  High PSMA avidity on 68Ga-PSMA PET/CT, defined as an SUVmax of ≥ 20&#xD;
&#xD;
          -  Normal baseline haematological function; haemoglobin 13.5-17.5g/dl), total white blood&#xD;
             cell count (4-11 x 109/l), platelets (150-400 x 109/l), neutrophils (2-7.5 x 109/l)&#xD;
             and lymphocytes (1-4 x 109/l)&#xD;
&#xD;
          -  Normal baseline serum biochemistry; sodium 135-145 nmol/l, potassium 3.5-5 nmol/l,&#xD;
             chloride 98-108 nmol/l, urea 3-9.2 nmol/l, creatinine 60-120μmol/l&#xD;
&#xD;
          -  Willing and able to comply with all study requirements including all treatments and&#xD;
             required assessments including follow up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prostate cancer with significant neuroendocrine or other rare variant pathology&#xD;
&#xD;
          -  Prior treatment for prostate cancer including radiotherapy and/or androgen deprivation&#xD;
             therapy.&#xD;
&#xD;
          -  Evidence of metastatic disease involving bone, viscera, or lymph nodes superior to the&#xD;
             common iliac bifurcation based on CT, MRI, WBBS or PSMA PET/CT.&#xD;
&#xD;
          -  Renal impairment [GFR &lt; 60mL/min].&#xD;
&#xD;
          -  Sjogren's syndrome.&#xD;
&#xD;
          -  A history of or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the patient's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the patient to participate, in the opinion of the treating investigator.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Declan Murphy</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael S Hofman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Violet</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>177Lu-PSMA</keyword>
  <keyword>Prostate Cancer</keyword>
  <keyword>Radionuclide Therapy</keyword>
  <keyword>Theranostics</keyword>
  <keyword>prostate specific membrane antigen</keyword>
  <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>177Lu-PSMA-617</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04430192
org study id: 19_245
nct id: NCT04430192
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This clinical trial will evaluate the dosimetry, efficacy and toxicity of Lu-PSMA in men with
      high PSMA-expressing high-risk localized or locoregional advanced prostate cancer (HRCaP)
      undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND)
This open label, phase I/II non-randomised clinical trial will evaluate the dosimetry,
      efficacy and toxicity of Lu-PSMA in men with high PSMA-expressing high-risk localized or
      locoregional advanced prostate cancer (HRCaP) undergoing radical prostatectomy (RP) and
      pelvic lymph node dissection (PLND). Patients will receive one or two cycles of 177Lu-PSMA
      followed by surgery. The primary objective is to determine the radiation absorbed dose in the
      prostate and involved lymph nodes. Secondary objectives include evaluating imaging response
      to therapy using PSMA-PET, biochemical response, pathological response, adverse effects of
      Lu-PSMA and surgical safety, and health-related Quality of Life (QoL).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the radiation absorbed dose in the prostate and involved lymph nodes following one or two administrations of Lu-PSMA in men with HRCaP prior to radical prostatectomy
time frame: Determined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA
description: Establishing the absorbed radiation dose in the prostate and involved lymph nodes (Gy)
measure: To evaluate the imaging response to therapy using PSMA-PET
time frame: 6 weeks following final administration of Lu-PSMA
description: PSMA PET response to therapy (complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease)
measure: To evaluate the biochemical response to therapy
time frame: 6 weeks following final administration of Lu-PSMA
description: PSA response
measure: To evaluate pathologic response in the prostate following prostatectomy
time frame: After prostatectomy, approximately 6 weeks from final Lu-PSMA administration
description: Pathological response (complete response, minimal residual disease)
measure: To evaluate toxicity of Lu-PSMA
time frame: Until 8 weeks after prostatectomy
description: Assessment of toxicity of Lu-PSMA using Common Terminology Criteria for Adverse Events (CTCAE) v5
measure: To evaluate the surgical safety of prostatectomy following Lu-PSMA
time frame: Until 8 weeks after prostatectomy
description: Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications
measure: To evaluate overall health-related Quality of Life (QoL)
time frame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
description: QoL indices will be scored using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
measure: To evaluate prostate cancer health-related Quality of Life (QoL)
time frame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
description: QoL indices will be scored using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire
measure: To evaluate patient function and bother after prostatectomy
time frame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
description: Indices will be scored using the Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire
measure: To determine the time to biochemical recurrence (BCR) [PSA>0.2 ng/mL post-RP]
time frame: To be determined as it is an exploratory endpoint up to 3 years
description: Biochemical recurrence (BCR) will be measured from the time of surgery to the first rise of the PSA to ≥0.2 ng/mL
measure: To determine the relationship between PSMA PET imaging parameters and absorbed dose
time frame: baseline PSMA PET within 45 days of Lu-PSMA administration
description: Determination of the relationship between screening PSMA PET imaging parameters including molecular tumour volume parameters and absorbed dose in the prostate and involved lymph nodes
measure: To identify tissue and blood and serum biomarkers associated with clinical outcomes
time frame: To be determined as it is an exploratory endpoint up to 3 years
description: Determination of relevant predictive biomarkers associated with treatment outcomes and response
arm group label: 177Lu-PSMA-617 followed by prostatectomy
arm group type: Experimental
description: 177Lu-PSMA-617 followed by prostatectomy
intervention type: Drug
intervention name: 177Lu-PSMA-617
description: Patients 1-10 will be given 5GBq of 177Lu-PSMA. Patients 11-20 will be given 2 cycles of 5GBq of 177Lu-PSMA, separated by 6 weeks.
arm group label: 177Lu-PSMA-617 followed by prostatectomy
other name: 177Lu-PSMA
other name: [177Lu]Lu-PSMA-617
other name: Lu-PSMA
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Declan Murphy
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
last name: Michael S Hofman
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
last name: John Violet
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: 177Lu-PSMA-617
sharing ipd: No