<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/NCT03828838</url>
  </required_header>
  <id_info>
    <org_study_id>NL62774.09L.r7</org_study_id>
    <nct_id>NCT03828838</nct_id>
  </id_info>
  <brief_title>Lutetium-177-PSMA-617 in Low Volume Metastatic Prostate Cancer</brief_title>
  <official_title>Pilot Study: Lutetium-177-PSMA-617 in Low Volume Metastatic Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</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>
      Radioligand therapy (RLT) using Lu-177 labelled PSMA is a promising new therapeutic approach&#xD;
      to treat metastatic prostate cancer. This tumor-specific treatment is directed against&#xD;
      prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer cells.&#xD;
      In the last few years, several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been&#xD;
      developed and are currently applied to treat metastatic castrate resistant prostate cancer&#xD;
      (mCRPC) patients. However, there are no prospective studies published so far using this&#xD;
      treatment approach in hormone sensitive setting. In this pilot study patients with hormone&#xD;
      sensitive prostate cancer who did not undergo hormonal treatment will be treated with Lu-177&#xD;
      PSMA-617.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Radioligand therapy (RLT) is a promising new therapeutic approach to treat metastatic&#xD;
      prostate cancer. This tumor-specific treatment is directed against prostate-specific membrane&#xD;
      antigen (PSMA), which is overexpressed in prostate cancer cells. In the last few years,&#xD;
      several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are&#xD;
      currently applied in nuclear medicine departments world-wide to treat metastatic castrate&#xD;
      resistant prostate cancer (mCRPC) patients.&#xD;
&#xD;
      A large retrospective study reported an overall biochemical response rate of 45% following&#xD;
      multiple 177Lu-PSMA RLT cycles in mCRPC patients, while 40% of patients already responded&#xD;
      after a single cycle. RLT with PSMA ligand PSMA-617 was generally well tolerated and 12% of&#xD;
      the patients suffered grade 3 to 4 hematological toxicity. In addition, mild and often&#xD;
      transient xerostomia occurred in 8%. These results were confirmed in a smaller scale&#xD;
      prospective study published recently.&#xD;
&#xD;
      Although these results are very promising, it is noteworthy that all currently&#xD;
      Lu-177-PSMA-617 RLT only has been evaluated in end stage prostate cancer patients to date. In&#xD;
      theory, RLT could be more effective in low volume disease because of the very high tumor&#xD;
      uptake of radioligands in small lesions. There are no published data so far evaluating the&#xD;
      therapeutic effect of Lu-177-PSMA-617 RLT in an earlier stage of the disease. Because of the&#xD;
      difference in tumor load between mCRPC patients and patients with low volume metastatic&#xD;
      disease, dosimetry and toxicity in these patients need evaluation. Here a clinical trial to&#xD;
      investigate the efficacy of Lu-177-PSMA-617 RLT in patients with low volume metastatic&#xD;
      prostate cancer, prior to the hormone insensitive state is proposed.&#xD;
&#xD;
      Objective: The aim of this study is to evaluate the dosimetry and toxicity of Lu-177-PSMA-617&#xD;
      RLT, in patients with low volume, hormone sensitive metastatic prostate cancer under&#xD;
      treatment condition. Ultimately, the goal of this study is to stabilize previously&#xD;
      progressive disease in these patients and to improve the quality of life by postponing the&#xD;
      need for androgen deprivation therapy (ADT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Actual">November 1, 2019</completion_date>
  <primary_completion_date type="Actual">November 1, 2019</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>Doses delivered to the tumors</measure>
    <time_frame>For cycle 1 (duration of one cycle is 56 days)</time_frame>
    <description>Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Doses delivered to the tumors</measure>
    <time_frame>For cycle 2 (duration of one cycle is 56 days)</time_frame>
    <description>Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Doses delivered to organs at risk</measure>
    <time_frame>For cycle 1 (duration of one cycle is 56 days)</time_frame>
    <description>Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Doses delivered to organs at risk</measure>
    <time_frame>For cycle 2 (duration of one cycle is 56 days)</time_frame>
    <description>Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PSA progression free survival</measure>
    <time_frame>Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle</time_frame>
    <description>PSA progression free survival, defined as the time from baseline to PSA progression, assessed using PCWG3 criteria on blood test results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uptake on prostate specific membrane antigen (PSMA) positron emission tomography (PET)</measure>
    <time_frame>Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle</time_frame>
    <description>Comparing the changes on baseline PSMA PET and after each cycle (defined according to EORTC PET response criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic progression free survival</measure>
    <time_frame>Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle</time_frame>
    <description>Radiographic progression free survival - defined as the time from baseline to radiographic progression (assessed using Prostate Cancer Working Group 3 (PCWG3) criteria for bone lesions and RECIST 1.1 for soft tissue lesions)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle</time_frame>
    <description>Health-related quality of life, assessed using a composite of the European Organisation of Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C-30)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Prostate Neoplasm</condition>
  <arm_group>
    <arm_group_label>Lu-177 PSMA-617</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two cycles with 3 and 3-6 GBq Lu-177 PSMA-617 (including 3D-dosimetry)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lu-177 PSMA-617</intervention_name>
    <description>Two cycles of Lu-177 PSMA (3GBq and 3-6 GBq)</description>
    <arm_group_label>Lu-177 PSMA-617</arm_group_label>
    <other_name>Lutetium-177 Prostate Specific Membrane Antigen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological proven adenocarcinoma of the prostate&#xD;
&#xD;
          -  Prior local therapy for prostate cancer&#xD;
&#xD;
          -  Biochemical recurrence or clinical progression after local therapy (PSA &gt; 0.2 µg/l),&#xD;
&#xD;
          -  PSA-DT &lt; 6 months&#xD;
&#xD;
          -  Gallium-68 (68Ga)-PSMA-PET-CT positive metastases in bones and/or lymph nodes&#xD;
             (N1/M1ab): ≥1, maximally 10 metastases (at least 1 lesion with a lesion size of ≥1 cm&#xD;
             to enable adequate dosimetry studies)&#xD;
&#xD;
          -  Local treatment for oligo-metastases with radiotherapy or surgery appears to be no&#xD;
             option anymore (due to prior treatment or the location of the metastatic lesions)&#xD;
&#xD;
          -  No prior hormonal therapy or chemotherapy; testosteron &gt; 1.7 nmol/l. Exception: local&#xD;
             prostate cancer treated with local radiotherapy plus adjuvant ADT; these patients need&#xD;
             to be stopped with ADT at least 3 months&#xD;
&#xD;
          -  No visceral metastases&#xD;
&#xD;
          -  Laboratory values:&#xD;
&#xD;
               -  White blood cells &gt; 3.5 x 109/l&#xD;
&#xD;
               -  Platelet count &gt; 150 x 109/l&#xD;
&#xD;
               -  Hemoglobin &gt; 6 mmol/l&#xD;
&#xD;
               -  Alanine transaminase, aspartate aminotransferase &lt; 3 x upper limit of normal&#xD;
&#xD;
               -  Modification of Diet in Renal Disease Study glomerular filtration rate ≥ 60&#xD;
                  ml/min&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No detectable lesions on the Ga-68 PSMA PET/CT with an uptake level below the liver&#xD;
             uptake.&#xD;
&#xD;
          -  A known subtype other than prostate adenocarcinoma&#xD;
&#xD;
          -  Any medical condition present that in the opinion of the investigator will affect&#xD;
             patients' clinical status when participating in this trial.&#xD;
&#xD;
          -  Prior hip replacement surgery potentially influencing performance of PSMA PET/CT and&#xD;
             nano Magnet Resonance Tomography (nMRI)&#xD;
&#xD;
          -  Contra-indication for MRI imaging (claustrophobia, implanted electric and electronic&#xD;
             devices (heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators),&#xD;
             intracranial metal clips, metallic bodies in the eye)&#xD;
&#xD;
          -  Contra-indication for Buscopan (allergy to hyoscine or any other ingredients of this&#xD;
             medication, allergy to to other atropines (e.g. atropine, scopolamine), myasthenia&#xD;
             gravis, enlarged colon, glaucoma or obstructive prostatic hypertrophy)&#xD;
&#xD;
          -  Additional contra-indications for the intravenous injection form of Buscopan (taking&#xD;
             blood thinning medication (e.g. warfarin, heparin), narrowing of the gastrointestinal&#xD;
             tract, fast heartbeat, angina or heart failure)&#xD;
&#xD;
          -  Contra-indication to glucagon (pheochromocytoma)&#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>James Nagarajah, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboudumc, Nijmegen, Nederland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radiology and Nuclear Medicine</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6525GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>November 13, 2019</last_update_submitted>
  <last_update_submitted_qc>November 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2019</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>177Lu-PSMA-617</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03828838
org study id: NL62774.09L.r7
nct id: NCT03828838
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Radioligand therapy (RLT) using Lu-177 labelled PSMA is a promising new therapeutic approach
      to treat metastatic prostate cancer. This tumor-specific treatment is directed against
      prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer cells.
      In the last few years, several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been
      developed and are currently applied to treat metastatic castrate resistant prostate cancer
      (mCRPC) patients. However, there are no prospective studies published so far using this
      treatment approach in hormone sensitive setting. In this pilot study patients with hormone
      sensitive prostate cancer who did not undergo hormonal treatment will be treated with Lu-177
      PSMA-617.
Radioligand therapy (RLT) is a promising new therapeutic approach to treat metastatic
      prostate cancer. This tumor-specific treatment is directed against prostate-specific membrane
      antigen (PSMA), which is overexpressed in prostate cancer cells. In the last few years,
      several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are
      currently applied in nuclear medicine departments world-wide to treat metastatic castrate
      resistant prostate cancer (mCRPC) patients.

      A large retrospective study reported an overall biochemical response rate of 45% following
      multiple 177Lu-PSMA RLT cycles in mCRPC patients, while 40% of patients already responded
      after a single cycle. RLT with PSMA ligand PSMA-617 was generally well tolerated and 12% of
      the patients suffered grade 3 to 4 hematological toxicity. In addition, mild and often
      transient xerostomia occurred in 8%. These results were confirmed in a smaller scale
      prospective study published recently.

      Although these results are very promising, it is noteworthy that all currently
      Lu-177-PSMA-617 RLT only has been evaluated in end stage prostate cancer patients to date. In
      theory, RLT could be more effective in low volume disease because of the very high tumor
      uptake of radioligands in small lesions. There are no published data so far evaluating the
      therapeutic effect of Lu-177-PSMA-617 RLT in an earlier stage of the disease. Because of the
      difference in tumor load between mCRPC patients and patients with low volume metastatic
      disease, dosimetry and toxicity in these patients need evaluation. Here a clinical trial to
      investigate the efficacy of Lu-177-PSMA-617 RLT in patients with low volume metastatic
      prostate cancer, prior to the hormone insensitive state is proposed.

      Objective: The aim of this study is to evaluate the dosimetry and toxicity of Lu-177-PSMA-617
      RLT, in patients with low volume, hormone sensitive metastatic prostate cancer under
      treatment condition. Ultimately, the goal of this study is to stabilize previously
      progressive disease in these patients and to improve the quality of life by postponing the
      need for androgen deprivation therapy (ADT).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Doses delivered to the tumors
time frame: For cycle 1 (duration of one cycle is 56 days)
description: Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors
measure: Doses delivered to the tumors
time frame: For cycle 2 (duration of one cycle is 56 days)
description: Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors
measure: Doses delivered to organs at risk
time frame: For cycle 1 (duration of one cycle is 56 days)
description: Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk
measure: Doses delivered to organs at risk
time frame: For cycle 2 (duration of one cycle is 56 days)
description: Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk
measure: PSA progression free survival
time frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
description: PSA progression free survival, defined as the time from baseline to PSA progression, assessed using PCWG3 criteria on blood test results.
measure: Uptake on prostate specific membrane antigen (PSMA) positron emission tomography (PET)
time frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
description: Comparing the changes on baseline PSMA PET and after each cycle (defined according to EORTC PET response criteria)
measure: Radiographic progression free survival
time frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
description: Radiographic progression free survival - defined as the time from baseline to radiographic progression (assessed using Prostate Cancer Working Group 3 (PCWG3) criteria for bone lesions and RECIST 1.1 for soft tissue lesions)
measure: Health-related quality of life
time frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
description: Health-related quality of life, assessed using a composite of the European Organisation of Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C-30)
arm group label: Lu-177 PSMA-617
arm group type: Experimental
description: Two cycles with 3 and 3-6 GBq Lu-177 PSMA-617 (including 3D-dosimetry)
intervention type: Drug
intervention name: Lu-177 PSMA-617
description: Two cycles of Lu-177 PSMA (3GBq and 3-6 GBq)
arm group label: Lu-177 PSMA-617
other name: Lutetium-177 Prostate Specific Membrane Antigen
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James Nagarajah, Prof.
role: Principal Investigator
affiliation: Radboudumc, Nijmegen, Nederland
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: 177Lu-PSMA-617
sharing ipd: Undecided