<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/NCT03822845</url>
  </required_header>
  <id_info>
    <org_study_id>201810754</org_study_id>
    <nct_id>NCT03822845</nct_id>
  </id_info>
  <brief_title>Evaluating the Clinical Accuracy of Gallium-68 PSMA PET/CT Imaging in Patients With Biochemical Recurrence of Prostate Cancer</brief_title>
  <official_title>Clinical Accuracy Assessment of 68Ga PSMA-HBED-CC PET in Patients With Biochemical Recurrence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Michael Graham PhD, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Iowa</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>
      This study investigates if a new drug (PSMA) makes prostate cancer easier to identify in&#xD;
      positron-emission tomography (PET) imaging. If this works, prostate cancer treatments can be&#xD;
      prescribed that match the location of the disease. PSMA is radiolabeled with Gallium-68&#xD;
      (Ga-68). This means a participant receives a small dose of radiation from the drug - less&#xD;
      than the annual radiation limit for a medical worker.&#xD;
&#xD;
      To test this new drug, participants will receive an injection of Ga-68 PSMA and then have a&#xD;
      PET scan. This PET scan, and the reported results, will be entered into the medical record&#xD;
      and shared with the treating oncologists.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study evaluates PSMA-HBED-CC labelled with Gallium-68, abbreviated 68Ga PSMA. This is a&#xD;
      radiotracer that attaches to receptors in the membrane of prostate cancer cells. The 68Ga&#xD;
      PSMA is identified using a positron emission tomography (PET) scanner. It is believed that&#xD;
      68Ga PSMA will identify prostate cancer more precisely than normal imaging methods (MRI, CT,&#xD;
      or ultrasound). Imaging is key to successful treatment - disease must be identified to be&#xD;
      treated.&#xD;
&#xD;
      The 68Ga PSMA will be tested in men who have biochemical recurrence of prostate cancer after&#xD;
      surgery or radiation treatment. Participants undergo the 68Ga PSMA PET scan before further&#xD;
      treatment. Clinical information, including any MRI, CT, or ultrasound imaging and&#xD;
      biopsy/surgery information, will be used to determine if the 68Ga PSMA PET imaging was better&#xD;
      than the standard imaging. The study team will collect this information for about 1 year&#xD;
      after the PSMA scan.&#xD;
&#xD;
      Depending on findings, participants may be invited back for a second 68Ga PSMA scan. This is&#xD;
      done if the first scan showed positive lymph nodes or soft tissue metastases but a surgery or&#xD;
      biopsy result does not.&#xD;
&#xD;
      The results from these scans will be shared with the participant. Results will also be&#xD;
      entered into the participant's medical record and shared with the treating oncologists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine sensitivity on a per-patient basis of 68Ga PSMA PET scans for detection of tumor location [CT.gov: ref: NCT03389451 for all comments]</measure>
    <time_frame>Up to 12 months after the 68Ga PSMA PET scan</time_frame>
    <description>Sensitivity will be determined on a per-patient basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine sensitivity on a per-region basis of 68Ga PSMA PET scans for detection of tumor location</measure>
    <time_frame>Up to 12 months after the 68Ga PSMA PET scan</time_frame>
    <description>Sensitivity will be determined on a per-region basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine positive predictive value on a per-subject and per-region basis of 68Ga PSMA PET scans for detection of tumor location</measure>
    <time_frame>3 and 12 months after 68Ga PSMA PET scan</time_frame>
    <description>Positive predictive value will be determined on a per-subject basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine sensitivity on per-subject and per-region basis of 68Ga PSMA-HBED-CC PET/CT for detecting tumor location, confirming with histopathology.</measure>
    <time_frame>3 and 12 months after 68Ga PSMA PET scan</time_frame>
    <description>Sensitivity value will be determined on a per-subject basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine detection rates on a per-subject basis of 68Ga PSMA-HBED-CC PET/CT when stratified by PSA value</measure>
    <time_frame>3 and 12 months after 68Ga PSMA PET scan</time_frame>
    <description>Detection rates will be evaluated on a per-subject basis, stratified by PSA values: 0.2 - &lt;0.5, 0.5 - &lt;1.0, 1.0 &lt;2.0, 2.0 - &lt;5.0, 5.0 or greater</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate adverse events of 68Ga PSMA PET scan</measure>
    <time_frame>through 24 hours post-injection of 68Ga PSMA</time_frame>
    <description>Adverse events will be determined through clinical assessment and categorized by CTCAE 4.03</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <condition>Prostatic Neoplasms, Castration-Resistant</condition>
  <arm_group>
    <arm_group_label>68Ga PSMA PET scan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ga-68 PSMA-HBED-CC PET/CT scan</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ga-68 PSMA-HBED-CC PET</intervention_name>
    <description>Ga-68 PSMA-HBED-CC is an investigational PET drug (radionuclide), that binds to the prostate specific receptors. The dose will be about 5mCi (range 3-7 mCi) and administered intravenously.</description>
    <arm_group_label>68Ga PSMA PET scan</arm_group_label>
    <other_name>Gallium-68 PSMA-HBED-CC PET scan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and willingness to provide informed consent.&#xD;
&#xD;
          -  Pathologically proven prostate adenocarcinoma.&#xD;
&#xD;
          -  Rising PSA after definitive therapy with a prostatectomy or radiation therapy&#xD;
             (external beam radiation therapy or brachytherapy).&#xD;
&#xD;
          -  If post-radical prostatectomy, a PSA level of &gt; 0.2 ng/mL measured more than 6 weeks&#xD;
             post-operatively with a second confirmatory persistent PSA &gt; 0.2 ng/mL.&#xD;
&#xD;
          -  If post-radiation therapy, a PSA level that is equal to, or greater than, a 2 mg/mL&#xD;
             rise above the lowest PSA value ('nadir').&#xD;
&#xD;
          -  A PSA level result within the last 2 months meeting criteria above.&#xD;
&#xD;
          -  Not receiving any other investigational agents (i.e., unlabeled drugs or drugs under&#xD;
             an IND for initial efficacy investigations).&#xD;
&#xD;
          -  No other malignancy within the past 2 years (skin basal cell or cutaneous superficial&#xD;
             squamous cell carcinoma or superficial bladder cancer are exempt from this criterion).&#xD;
&#xD;
          -  Karnofsky performance status greater than or equal to 50 (ECOG/WHO 0, 1, or 2) within&#xD;
             the last 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cannot receive furosemide.&#xD;
&#xD;
          -  History of Stevens-Johnson syndrome.&#xD;
&#xD;
          -  History or diagnosis of Paget's disease.&#xD;
&#xD;
          -  Malignancy other than current disease under study.&#xD;
&#xD;
          -  Allergy to sulfa or sulfa-containing medications.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#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>Michael M Graham, Ph.D., MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Iowa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Iowa Hospitals &amp; Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kubler H, Beer AJ, Schwaiger M, Eiber M. Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. J Urol. 2016 May;195(5):1436-1443. doi: 10.1016/j.juro.2015.12.025. Epub 2015 Dec 9.</citation>
    <PMID>26682756</PMID>
  </reference>
  <reference>
    <citation>van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, Stricker PD. Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int. 2017 Feb;119(2):209-215. doi: 10.1111/bju.13540. Epub 2016 Jun 18.</citation>
    <PMID>27207581</PMID>
  </reference>
  <reference>
    <citation>Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kubler H, Haberkorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M. Evaluation of Hybrid (6)(8)Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med. 2015 May;56(5):668-74. doi: 10.2967/jnumed.115.154153. Epub 2015 Mar 19. Erratum In: J Nucl Med. 2016 Aug;57(8):1325.</citation>
    <PMID>25791990</PMID>
  </reference>
  <reference>
    <citation>Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, Eisenhut M, Boxler S, Hadaschik BA, Kratochwil C, Weichert W, Kopka K, Debus J, Haberkorn U. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):197-209. doi: 10.1007/s00259-014-2949-6. Epub 2014 Nov 20.</citation>
    <PMID>25411132</PMID>
  </reference>
  <reference>
    <citation>Green MA, Eitel JA, Fletcher JW, Mathias CJ, Tann MA, Gardner T, Koch MO, Territo W, Polson H, Hutchins GD. Estimation of radiation dosimetry for 68Ga-HBED-CC (PSMA-11) in patients with suspected recurrence of prostate cancer. Nucl Med Biol. 2017 Mar;46:32-35. doi: 10.1016/j.nucmedbio.2016.11.002. Epub 2016 Nov 4.</citation>
    <PMID>28012435</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>March 1, 2023</last_update_submitted>
  <last_update_submitted_qc>March 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Iowa</investigator_affiliation>
    <investigator_full_name>Michael Graham PhD, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Nuclear scans</keyword>
  <keyword>PET imaging</keyword>
  <keyword>prostate cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Prostatic Neoplasms, Castration-Resistant</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Edetic Acid</mesh_term>
    <mesh_term>Gallium 68 PSMA-11</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Codified data will be archived and stored in an imaging repository with limited metadata for analysis. A data sharing contract for a HIPAA limited dataset will need to be executed prior to data sharing.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Reviewed upon request; may not be immediately available depending upon accrual and study's completion status. Data will be archived for research purposes.</ipd_time_frame>
    <ipd_access_criteria>Individuals seeking use of these data should contact the study chair. A contract may be necessary for data sharing.</ipd_access_criteria>
  </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/NCT03822845
org study id: 201810754
nct id: NCT03822845
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study investigates if a new drug (PSMA) makes prostate cancer easier to identify in
      positron-emission tomography (PET) imaging. If this works, prostate cancer treatments can be
      prescribed that match the location of the disease. PSMA is radiolabeled with Gallium-68
      (Ga-68). This means a participant receives a small dose of radiation from the drug - less
      than the annual radiation limit for a medical worker.

      To test this new drug, participants will receive an injection of Ga-68 PSMA and then have a
      PET scan. This PET scan, and the reported results, will be entered into the medical record
      and shared with the treating oncologists.
This study evaluates PSMA-HBED-CC labelled with Gallium-68, abbreviated 68Ga PSMA. This is a
      radiotracer that attaches to receptors in the membrane of prostate cancer cells. The 68Ga
      PSMA is identified using a positron emission tomography (PET) scanner. It is believed that
      68Ga PSMA will identify prostate cancer more precisely than normal imaging methods (MRI, CT,
      or ultrasound). Imaging is key to successful treatment - disease must be identified to be
      treated.

      The 68Ga PSMA will be tested in men who have biochemical recurrence of prostate cancer after
      surgery or radiation treatment. Participants undergo the 68Ga PSMA PET scan before further
      treatment. Clinical information, including any MRI, CT, or ultrasound imaging and
      biopsy/surgery information, will be used to determine if the 68Ga PSMA PET imaging was better
      than the standard imaging. The study team will collect this information for about 1 year
      after the PSMA scan.

      Depending on findings, participants may be invited back for a second 68Ga PSMA scan. This is
      done if the first scan showed positive lymph nodes or soft tissue metastases but a surgery or
      biopsy result does not.

      The results from these scans will be shared with the participant. Results will also be
      entered into the participant's medical record and shared with the treating oncologists.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Determine sensitivity on a per-patient basis of 68Ga PSMA PET scans for detection of tumor location [CT.gov: ref: NCT03389451 for all comments]
time frame: Up to 12 months after the 68Ga PSMA PET scan
description: Sensitivity will be determined on a per-patient basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.
measure: Determine sensitivity on a per-region basis of 68Ga PSMA PET scans for detection of tumor location
time frame: Up to 12 months after the 68Ga PSMA PET scan
description: Sensitivity will be determined on a per-region basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.
measure: Determine positive predictive value on a per-subject and per-region basis of 68Ga PSMA PET scans for detection of tumor location
time frame: 3 and 12 months after 68Ga PSMA PET scan
description: Positive predictive value will be determined on a per-subject basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.
measure: Determine sensitivity on per-subject and per-region basis of 68Ga PSMA-HBED-CC PET/CT for detecting tumor location, confirming with histopathology.
time frame: 3 and 12 months after 68Ga PSMA PET scan
description: Sensitivity value will be determined on a per-subject basis of 68Ga PSMA PET scan for detection of tumor sites, confirming against imaging, clinical follow-up, and histopathology when available.
measure: Determine detection rates on a per-subject basis of 68Ga PSMA-HBED-CC PET/CT when stratified by PSA value
time frame: 3 and 12 months after 68Ga PSMA PET scan
description: Detection rates will be evaluated on a per-subject basis, stratified by PSA values: 0.2 - <0.5, 0.5 - <1.0, 1.0 <2.0, 2.0 - <5.0, 5.0 or greater
measure: Evaluate adverse events of 68Ga PSMA PET scan
time frame: through 24 hours post-injection of 68Ga PSMA
description: Adverse events will be determined through clinical assessment and categorized by CTCAE 4.03
arm group label: 68Ga PSMA PET scan
arm group type: Experimental
description: Ga-68 PSMA-HBED-CC PET/CT scan
intervention type: Drug
intervention name: Ga-68 PSMA-HBED-CC PET
description: Ga-68 PSMA-HBED-CC is an investigational PET drug (radionuclide), that binds to the prostate specific receptors. The dose will be about 5mCi (range 3-7 mCi) and administered intravenously.
arm group label: 68Ga PSMA PET scan
other name: Gallium-68 PSMA-HBED-CC PET scan
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael M Graham, Ph.D., MD
role: Study Chair
affiliation: University of Iowa
facility: 
country: United States
citation: Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kubler H, Beer AJ, Schwaiger M, Eiber M. Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. J Urol. 2016 May;195(5):1436-1443. doi: 10.1016/j.juro.2015.12.025. Epub 2015 Dec 9.
PMID: 26682756
citation: van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, Stricker PD. Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int. 2017 Feb;119(2):209-215. doi: 10.1111/bju.13540. Epub 2016 Jun 18.
PMID: 27207581
citation: Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kubler H, Haberkorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M. Evaluation of Hybrid (6)(8)Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med. 2015 May;56(5):668-74. doi: 10.2967/jnumed.115.154153. Epub 2015 Mar 19. Erratum In: J Nucl Med. 2016 Aug;57(8):1325.
PMID: 25791990
citation: Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, Eisenhut M, Boxler S, Hadaschik BA, Kratochwil C, Weichert W, Kopka K, Debus J, Haberkorn U. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):197-209. doi: 10.1007/s00259-014-2949-6. Epub 2014 Nov 20.
PMID: 25411132
citation: Green MA, Eitel JA, Fletcher JW, Mathias CJ, Tann MA, Gardner T, Koch MO, Territo W, Polson H, Hutchins GD. Estimation of radiation dosimetry for 68Ga-HBED-CC (PSMA-11) in patients with suspected recurrence of prostate cancer. Nucl Med Biol. 2017 Mar;46:32-35. doi: 10.1016/j.nucmedbio.2016.11.002. Epub 2016 Nov 4.
PMID: 28012435
responsible party type: Sponsor-Investigator
investigator affiliation: University of Iowa
investigator full name: Michael Graham PhD, MD
investigator title: Professor
mesh term: Neoplasms
mesh term: Prostatic Neoplasms
mesh term: Prostatic Neoplasms, Castration-Resistant
mesh term: Recurrence
mesh term: Edetic Acid
mesh term: Gallium 68 PSMA-11
sharing ipd: Yes
ipd description: Codified data will be archived and stored in an imaging repository with limited metadata for analysis. A data sharing contract for a HIPAA limited dataset will need to be executed prior to data sharing.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Reviewed upon request; may not be immediately available depending upon accrual and study's completion status. Data will be archived for research purposes.
ipd access criteria: Individuals seeking use of these data should contact the study chair. A contract may be necessary for data sharing.