xml: <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/NCT06004661</url>
    </required_header>
    <id_info>
      <org_study_id>CAAA617A12202</org_study_id>
      <secondary_id>2023-503925-20-00</secondary_id>
      <nct_id>NCT06004661</nct_id>
    </id_info>
    <brief_title>Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function</brief_title>
    <official_title>An Open-label Dosimetry, Biodistribution, Tolerability and Safety Study of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Moderately and Severely Impaired and With Normal Renal Function.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novartis Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Novartis</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will address health authorities' requests to determine whether moderate and severe&#xD;
        renal impairment have an impact on the biodistribution, dosimetry and safety of lutetium&#xD;
        (177Lu) vipivotide tetraxetan (AAA617) administered to participants with progressive&#xD;
        PSMA-positive metastatic castration-resistant prostate cancer. The study will also&#xD;
        characterize the risk of QT prolongation of AAA617 in this participant population.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This open-label, non-randomized, multicenter, single arm phase II study in mCRPC participants&#xD;
        aims to better characterize the safety and tolerability of AAA617 in participants with&#xD;
        moderate and severe renal impairment compared with normal renal function. Since both severe&#xD;
        and moderate renal impairment have very low incidence within mCRPC participant population&#xD;
        compared to participants with normal renal function, the enrollment will occur in parallel&#xD;
        for the 3 cohorts; participants will be stratified in one of the three cohorts (A:normal, B:&#xD;
        moderate or C: severe) based on their eGFR at screening.&#xD;
  &#xD;
        All participants will undergo a 68Ga-PSMA-11 PET/CT scan at screening to confirm PSMA&#xD;
        positivity.&#xD;
  &#xD;
        Participants will receive a dose of 7.4 GBq (±10%) of AAA617 once every 6 weeks for a planned&#xD;
        6 cycles for cohorts A and B and for 3 cycles (and 3 additional cycles) for cohort C.&#xD;
  &#xD;
        After treatment period, participants will be asked to join a long term follow up (LTFU) study&#xD;
        to monitor their safety up to 10 years after the 1st dose of AAA617. In case of the LTFU&#xD;
        study is not available at the time of end of treatment period (safety follow-up visit),&#xD;
        participants will continue in Long Term Follow-up period in this study for up to one year&#xD;
        until they can roll over into the separate LTFU study.&#xD;
  &#xD;
        The primary outcome will be to determine the effect of radiation absorption in kidney and&#xD;
        other organs at risk as well as the concentration in blood and radioactivity in urine in&#xD;
        PSMA- positive mCRPC participants with moderate and severe renal impairment. In addition, the&#xD;
        study will assess the relationship between drug concentrations and QTcF.&#xD;
  &#xD;
        20 participants with 6 countries are expected to be included with at least 6 evaluable&#xD;
        participantts per cohort.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 29, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 20, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Participants confirmed for enrollment in IRT will be stratified in one of the three cohorts based on eGFR calculated (MDRD formula) at screening:&#xD;
  Cohort A: normal renal function eGFR &gt;= 90 mL/min,&#xD;
  Cohort B: moderate renal impairment eGFR &gt;= 30 to =&lt; 59 mL/min&#xD;
  Cohort C: severe renal impairment eGFR &gt;= 15 to =&lt; 29 mL/min.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Absorbed radiation dose in kidneys and selected organs</measure>
      <time_frame>Up to 36 weeks</time_frame>
      <description>The absorbed dose in kidneys and selected organs will be summarized with descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Concentrations of AAA617 in blood over time</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Blood concentration of [177Lu]Lu-PSMA-617 will be summarized with descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time of maximum observed drug concentration occurrence (Tmax) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Observed maximum plasma concentration (Cmax) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Terminal elimination half-life (T^1/2) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Total systemic clearance for intravenous administration (CL) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Volume of distribution during the terminal phase following intravenous elimination (Vz) of 177Lu-PSMA-617</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Renal clearance of 177Lu-PSMA-617</measure>
      <time_frame>Cycle 1 Day 1: end of infusion to 2 hours, 2 hours to 4 hours, 4 hours to 24 hours, 24 hours to 48 hours, 48 hours to 72 hours post infusion. Cycle = 6 weeks</time_frame>
      <description>The volume of each urine collection will be measured and the radioactivity concentration (KBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of infusion until 72h.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in eGFR</measure>
      <time_frame>at screening and at every visit, assessed up to 1 year after last treatment</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose modifications for AAA617</measure>
      <time_frame>Up to 36 weeks</time_frame>
      <description>Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose intensity for AAA617</measure>
      <time_frame>Up to 36 weeks</time_frame>
      <description>Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in QTcF interval (ΔQTcF)</measure>
      <time_frame>During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relationship between drug concentrations and QTcF</measure>
      <time_frame>During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks</time_frame>
      <description>The relationship between 177Lu-PSMA-617 plasma concentrations and ΔQTcF will be investigated using a linear mixed-effects modeling approach with ΔQTcF as the dependent variable, time-matched 177Lu-PSMA-617 plasma concentration as the explanatory variable, centered baseline QTcF (i.e., baseline QTcF for individual patient minus the population mean baseline QTcF for all patients) as an additional covariate, a fixed intercept, and a random intercept and slope per patient, when applicable (Garnett et al1).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR)</measure>
      <time_frame>From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks</time_frame>
      <description>Objective response rate (ORR) (CR + PR) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions as per local review and according to PCWG3-modified RECIST v1.1. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks</time_frame>
      <description>Disease Control Rate (DCR) (CR + PR + stable disease [SD]) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions. DCR will be analyzed using the same analytical conventions as ORR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSA50 response</measure>
      <time_frame>From screening up to 1 year</time_frame>
      <description>PSA50 response is defined as the proportion of participants who have a &gt;= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement &gt;= 4 weeks later</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Metastatic Castration-Resistant Prostate Cancer (mCRPC)</condition>
    <arm_group>
      <arm_group_label>AAA617</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for 3 to 6 cycles according to eGFR calculation at screening and radiation absorbed dose results from Cycle1 Day1.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AAA617</intervention_name>
      <description>Administered intravenously once every cycles (1 cycle = 6 weeks)</description>
      <arm_group_label>AAA617</arm_group_label>
      <other_name>Pluvicto</other_name>
      <other_name>177Lu-Lu-PSMA-617</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>68Ga-PSMA-11</intervention_name>
      <description>Single intravenous dose of approximately 150 MBq</description>
      <arm_group_label>AAA617</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            1. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2&#xD;
  &#xD;
            2. 68Ga-PSMA-11 Positron emission tomography (PET)/CT scan positive, and eligible as&#xD;
               determined by the sponsor's central reader.&#xD;
  &#xD;
            3. A castrate level of serum/plasma testosterone (&lt; 50 ng/dL or &lt; 1.7 nmol/L).&#xD;
  &#xD;
            4. Documented progressive mCRPC will be based on at least 1 of the following criteria:&#xD;
  &#xD;
                 -  Serum/plasma Prostate-Specific Antigen (PSA) progression defined as 2 consecutive&#xD;
                    increases in PSA over a previous reference value measured at least 1 week prior.&#xD;
                    The minimal start value is 2.0 ng/mL&#xD;
  &#xD;
                 -  Soft-tissue progression defined as an increase &gt;= 20% in the sum of the diameter&#xD;
                    (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all&#xD;
                    target lesions based on the smallest SOD since treatment started or the&#xD;
                    appearance of one or more new lesions.&#xD;
  &#xD;
                 -  Progression of bone disease: evaluable disease or new bone lesions(s) by bone&#xD;
                    scan (2+2 PCWG3 criteria)&#xD;
  &#xD;
            5. Documented stable renal disease without evidence of renal progressive disease (stable&#xD;
               renal disease is defined as no significant change, such as a stable eGFR, within 4&#xD;
               weeks prior to study entry)&#xD;
  &#xD;
            6. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD)&#xD;
               equation:&#xD;
  &#xD;
                 -  Normal renal function: participants with eGFR &gt;= 90 mL/min&#xD;
  &#xD;
                 -  Moderate renal impairment: participants with eGFR &gt;= 30 to =&lt; 59 mL/min&#xD;
  &#xD;
                 -  Severe renal impairment: participants with eGFR &gt;= 15 to =&lt; 29 mL/min&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            1. Previous treatment with PSMA-targeted radioligand therapy.&#xD;
  &#xD;
            2. Previous treatment with any of the following within 6 months of enrollment&#xD;
               confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or&#xD;
               hemi-body irradiation.&#xD;
  &#xD;
            3. Use of agents known to prolong the QT interval from start of screening to end of Cycle&#xD;
               1, unless they can be permanently discontinued for the duration of study.&#xD;
  &#xD;
            4. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any&#xD;
               level of urinary obstruction requiring indwelling/condom catheters. Participants with&#xD;
               postrenal impairment, like obstructions, retroperitoneal fibrosis (eg after&#xD;
               prostectomy) must be excluded or first resolved to ≤ Grade 1.&#xD;
  &#xD;
            5. History or current diagnosis of ECG abnormalities indicating significant risk of&#xD;
               safety for participants participating in the study such as:&#xD;
  &#xD;
                 -  Concomitant clinically significant cardiac arrhythmias, e.g. sustained&#xD;
                    ventricular tachycardia, and clinically significant second- or third-degree AV&#xD;
                    block without a pacemaker.&#xD;
  &#xD;
                 -  History of familial long QT syndrome or known family history of Torsades de&#xD;
                    Pointe.&#xD;
  &#xD;
                 -  Resting heart rate (physical exam or 12 lead ECG) &lt;60 bpm&#xD;
  &#xD;
          Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Prostate cancer</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Novartis Pharmaceuticals</last_name>
      <role>Study Director</role>
      <affiliation>Novartis Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>1-888-669-6682</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 29, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer</keyword>
    <keyword>Prostate-specific membrane antigen</keyword>
    <keyword>PSMA</keyword>
    <keyword>Metastatic Castration-Resistant Prostate Cancer</keyword>
    <keyword>mCRPC</keyword>
    <keyword>Renal impairment</keyword>
    <keyword>Moderately impaired renal function</keyword>
    <keyword>Severely impaired renal function</keyword>
    <keyword>Normal renal function</keyword>
    <keyword>lutetium (177Lu) vipivotide tetraxetan</keyword>
    <keyword>AAA617</keyword>
    <keyword>Dosimetry</keyword>
    <keyword>QTc prolongation</keyword>
    <keyword>post marketing requirement</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>Gallium 68 PSMA-11</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
  This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06004661
  org study id: CAAA617A12202
  secondary id: 2023-503925-20-00
  nct id: NCT06004661
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This study will address health authorities' requests to determine whether moderate and severe
        renal impairment have an impact on the biodistribution, dosimetry and safety of lutetium
        (177Lu) vipivotide tetraxetan (AAA617) administered to participants with progressive
        PSMA-positive metastatic castration-resistant prostate cancer. The study will also
        characterize the risk of QT prolongation of AAA617 in this participant population.
  This open-label, non-randomized, multicenter, single arm phase II study in mCRPC participants
        aims to better characterize the safety and tolerability of AAA617 in participants with
        moderate and severe renal impairment compared with normal renal function. Since both severe
        and moderate renal impairment have very low incidence within mCRPC participant population
        compared to participants with normal renal function, the enrollment will occur in parallel
        for the 3 cohorts; participants will be stratified in one of the three cohorts (A:normal, B:
        moderate or C: severe) based on their eGFR at screening.
  
        All participants will undergo a 68Ga-PSMA-11 PET/CT scan at screening to confirm PSMA
        positivity.
  
        Participants will receive a dose of 7.4 GBq (±10%) of AAA617 once every 6 weeks for a planned
        6 cycles for cohorts A and B and for 3 cycles (and 3 additional cycles) for cohort C.
  
        After treatment period, participants will be asked to join a long term follow up (LTFU) study
        to monitor their safety up to 10 years after the 1st dose of AAA617. In case of the LTFU
        study is not available at the time of end of treatment period (safety follow-up visit),
        participants will continue in Long Term Follow-up period in this study for up to one year
        until they can roll over into the separate LTFU study.
  
        The primary outcome will be to determine the effect of radiation absorption in kidney and
        other organs at risk as well as the concentration in blood and radioactivity in urine in
        PSMA- positive mCRPC participants with moderate and severe renal impairment. In addition, the
        study will assess the relationship between drug concentrations and QTcF.
  
        20 participants with 6 countries are expected to be included with at least 6 evaluable
        participantts per cohort.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Participants confirmed for enrollment in IRT will be stratified in one of the three cohorts based on eGFR calculated (MDRD formula) at screening:
  Cohort A: normal renal function eGFR >= 90 mL/min,
  Cohort B: moderate renal impairment eGFR >= 30 to =< 59 mL/min
  Cohort C: severe renal impairment eGFR >= 15 to =< 29 mL/min.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Absorbed radiation dose in kidneys and selected organs
  time frame: Up to 36 weeks
  description: The absorbed dose in kidneys and selected organs will be summarized with descriptive statistics.
  measure: Concentrations of AAA617 in blood over time
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Blood concentration of [177Lu]Lu-PSMA-617 will be summarized with descriptive statistics.
  measure: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
  measure: Time of maximum observed drug concentration occurrence (Tmax) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
  measure: Observed maximum plasma concentration (Cmax) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
  measure: Terminal elimination half-life (T^1/2) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics
  measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
  measure: Total systemic clearance for intravenous administration (CL) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
  measure: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 177Lu-PSMA-617
  time frame: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (156-168 h post infusion). Cycle=6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
  measure: Renal clearance of 177Lu-PSMA-617
  time frame: Cycle 1 Day 1: end of infusion to 2 hours, 2 hours to 4 hours, 4 hours to 24 hours, 24 hours to 48 hours, 48 hours to 72 hours post infusion. Cycle = 6 weeks
  description: The volume of each urine collection will be measured and the radioactivity concentration (KBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of infusion until 72h.
  measure: Change from baseline in eGFR
  time frame: at screening and at every visit, assessed up to 1 year after last treatment
  measure: Dose modifications for AAA617
  time frame: Up to 36 weeks
  description: Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics.
  measure: Dose intensity for AAA617
  time frame: Up to 36 weeks
  description: Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.
  measure: Change from baseline in QTcF interval (ΔQTcF)
  time frame: During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks
  measure: Relationship between drug concentrations and QTcF
  time frame: During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks
  description: The relationship between 177Lu-PSMA-617 plasma concentrations and ΔQTcF will be investigated using a linear mixed-effects modeling approach with ΔQTcF as the dependent variable, time-matched 177Lu-PSMA-617 plasma concentration as the explanatory variable, centered baseline QTcF (i.e., baseline QTcF for individual patient minus the population mean baseline QTcF for all patients) as an additional covariate, a fixed intercept, and a random intercept and slope per patient, when applicable (Garnett et al1).
  measure: Overall Response Rate (ORR)
  time frame: From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks
  description: Objective response rate (ORR) (CR + PR) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions as per local review and according to PCWG3-modified RECIST v1.1. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.
  measure: Disease Control Rate (DCR)
  time frame: From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks
  description: Disease Control Rate (DCR) (CR + PR + stable disease [SD]) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions. DCR will be analyzed using the same analytical conventions as ORR.
  measure: PSA50 response
  time frame: From screening up to 1 year
  description: PSA50 response is defined as the proportion of participants who have a >= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement >= 4 weeks later
  arm group label: AAA617
  arm group type: Experimental
  description: Participants will receive a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for 3 to 6 cycles according to eGFR calculation at screening and radiation absorbed dose results from Cycle1 Day1.
  intervention type: Drug
  intervention name: AAA617
  description: Administered intravenously once every cycles (1 cycle = 6 weeks)
  arm group label: AAA617
  other name: Pluvicto
  other name: 177Lu-Lu-PSMA-617
  intervention type: Drug
  intervention name: 68Ga-PSMA-11
  description: Single intravenous dose of approximately 150 MBq
  arm group label: AAA617
  criteria: 
  gender: Male
  gender based: Yes
  gender description: Prostate cancer
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  role: Study Director
  affiliation: Novartis Pharmaceuticals
  last name: Novartis Pharmaceuticals
  phone: 1-888-669-6682
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  responsible party type: Sponsor
  mesh term: Prostatic Neoplasms
  mesh term: Gallium 68 PSMA-11
  sharing ipd: Yes
  ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
  This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com