<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/NCT02232685</url>
  </required_header>
  <id_info>
    <org_study_id>MAM_PROSTAGE1</org_study_id>
    <nct_id>NCT02232685</nct_id>
  </id_info>
  <brief_title>Whole Body Bone Scan vs 18F-Choline PET/CT in Prostate Cancer</brief_title>
  <official_title>Whole Body Bone Scan vs 18F-Choline PET/CT, Better Detection of Bone Metastases in Prostate Cancer Patients, PROSTAGE I</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostate cancer is currently the leading newly diagnosed cancer in the industrialized world.&#xD;
      Treatment of prostate cancer is highly dependent on the stage of the disease. Current methods&#xD;
      for staging are known to be inaccurate. Prior studies from our department suggest that PET/CT&#xD;
      is useful in staging of bone metastases in patients with prostate cancer. The aim of this&#xD;
      study is to test the usefulness of Choline PET/CT for the staging of bone metastases compared&#xD;
      to current standard methods in patients with newly diagnosed prostate cancer.&#xD;
&#xD;
      Better initial staging will result in better treatment of the individual patient. If we are&#xD;
      able to develop a more accurate method of staging patients with undetected metastases on&#xD;
      current staging will be spared of the side-effects associated with current treatment -&#xD;
      impotence, incontinence, radiation damage etc.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Introduction. Cancer of the prostate (PCa) is currently the leading newly diagnosed&#xD;
           cancer and the second most common cause of cancer deaths among men in the industrialized&#xD;
           world . In Denmark alone more than 4000 men are yearly diagnosed with PCa . As PCa&#xD;
           primarily affects elderly patients, one can assume that PCa will become one of the most&#xD;
           important medical issues in the developed world due to the already high incidence&#xD;
           combined with a growing population of elderly men.&#xD;
&#xD;
           The aetiology of the disease is not well understood. In its most common form PCa evolves&#xD;
           from the glandular tissue of the prostate. Metastatic spread will most commonly happen&#xD;
           as lymphogenous spread to the regional lymph nodes or as haematogenous spread to the red&#xD;
           bone marrow .&#xD;
&#xD;
           Intended curative treatment of PCa is associated with considerable side effects, in&#xD;
           particular incontinence, impotence and radiation damage to the surrounding tissues.&#xD;
           Furthermore, over 30% of patients with organ-confined disease, which was treated with&#xD;
           radical prostatectomy, will have biochemical relapse within 10 years . Relapse may be&#xD;
           due to local recurrent disease suggesting poor surgical quality or poor initial staging&#xD;
           with undetected metastases at the time of treatment.&#xD;
&#xD;
           At diagnosis patients are stratified as having low, intermediary or high risk of&#xD;
           dissieminatio according to D'Amico. Patients with intermediate or high risk of&#xD;
           dissemination will be examined further with whole-body bone scintigraphy (WBS) and&#xD;
           pelvic lymph node dissection (PLND).&#xD;
&#xD;
        2. Background. 2.1. Current staging and limitations. WBS has been the examination of choice&#xD;
           for evaluation of potential dissemination to bone. WBS utilizes 99mTc-labeled methylene&#xD;
           diphosphonate (99mTc-MDP) that binds to the bone matrix formed by the osteoblasts. Gamma&#xD;
           cameras detect the γ-radiation emitted by the decaying tracer thereby creating a&#xD;
           2-dimentional image depicting local osteoblast activity .&#xD;
&#xD;
           Several limitations apply to the use of WBS in staging of patients with PCa. Sensitivity&#xD;
           has reported as low as 39% in lesion-based analysis in patients with a low number of&#xD;
           lesions . This combines with a low sensitivity due to many equivocal lesions caused by&#xD;
           other bone pathology than metastasis.&#xD;
&#xD;
           Sensitivity and specificity is improved by the use of single-photon emission computed&#xD;
           tomography (SPECT), where the same tracer as with WBS is used to generate a&#xD;
           three-dimensional image using a rotating gamma camera. This method also gives better&#xD;
           anatomical information on the exact position of a potential metastasis.&#xD;
&#xD;
           The examination of choice for the evaluation of potential metastases to lymph nodes is&#xD;
           extended PLND . This procedure is done either prior to radiotherapy or during&#xD;
           prostatectomy in patients with intermediate or high risk of dissemination. The optimal&#xD;
           extent of the dissection is debated. The extended PLND performed at our institution&#xD;
           includes the nodes in the obturator fossa, the nodes over the external iliac artery and&#xD;
           vein, the nodes around the internal iliac artery and the nodes along the common iliac&#xD;
           artery up to the crossing of the ureter. This dissection is assumed to include&#xD;
           approximately 75% of lymph nodes known to harbor primary prostatic lymph node metastases&#xD;
           . Extended PLND is surgically demanding with risk of lymphocele formation, infectious&#xD;
           complications and severe bleeding due the lymph nodes' close proximity to the large&#xD;
           vessels in the pelvis. All in all extended PLND is perhaps the best option for lymph&#xD;
           node staging of PCa but it cannot be considered as optimal due to the above-mentioned&#xD;
           issues.&#xD;
&#xD;
           2.2 Positron Emission Tomography (PET). Positron Emission Tomography combined with&#xD;
           Computerized Tomography (PET/CT) is a well-established tool in diagnosing and staging of&#xD;
           several types of cancer . PET is an imaging technique where pairs of gamma rays emitted&#xD;
           by positron-emitting radionuclide tracer are detected, producing a three-dimensional&#xD;
           image of tracer concentration based on the amount of gamma rays emitted. The radioactive&#xD;
           tracer is coupled to a biologically active molecule depending on the organ or metabolic&#xD;
           process of interest . These images can then be fused with CT to create a combined&#xD;
           functional and high-resolution anatomical image. Several tracers have been developed for&#xD;
           use in cancer diagnostics and staging. As of now, PET/CT has no generally accepted role&#xD;
           in the diagnosing or staging of PCa neither in Europe nor in the US .&#xD;
&#xD;
           2.2.1 Choline. Choline is a precursor for phosphatidylcholine, a phospholipid that is&#xD;
           integrated in the cell membrane making it a marker for cell membrane turnover and&#xD;
           metabolism . 11C-Choline was first used as a PET tracer in 1997 . Since then many&#xD;
           studies have been performed with 11C-Choline and later 18F-Choline (FCH) having&#xD;
           approximately the same properties as 11C-Choline, but with a longer half-life (110 min&#xD;
           vs. 20 min) making it more versatile in every-day use. A recent study from our&#xD;
           department tested the use of FCH-PET/CT in detecting lymph node metastasis in 210&#xD;
           patients with PCa . The study concluded that FCH-PET/CT was not ideally suited for lymph&#xD;
           node staging but could give additional information about bone metastasis. Several other&#xD;
           investigators have also implied this , . A likely reason for the better detection of&#xD;
           metastasis to the bone is that bone metastasis in an early stage is actually bone-marrow&#xD;
           metastases rather than bone matrix metastasis and that it most likely that bone-marrow&#xD;
           metastases proceed to bone matrix metastases. These will not be detectable by WBS (and&#xD;
           probably not by CT and MRI either). Larger prospective series on the use of FCH-PET/CT&#xD;
           for imaging of bone metastasis in PCa-patients have not yet been produced.&#xD;
&#xD;
        3. Trial objective. To compare the diagnostic accuracy in detecting bone metastases of WBS,&#xD;
           SPECT and FCH PET/CT in 280 patients with newly diagnosed PCa with intermediate or high&#xD;
           risk of disseminated disease&#xD;
&#xD;
        4. Method. The patients will have two scans performed, first one with two acquisitions&#xD;
           using only one administration of tracer i.e. a WBS followed by a SPECT acquisition and&#xD;
           on another day a FCH-PET/CT. Image acquisition will be performed approximately 60 min&#xD;
           after intravenous injection of the tracer.&#xD;
&#xD;
      The scans are performed in random order within three weeks and the images interpreted by a&#xD;
      specialist in nuclear medicine and a specialist in radiology. Patients who already have had&#xD;
      WBS performed will only have a FCH-PET/CT performed.&#xD;
&#xD;
      Images are interpreted based on visual evaluation with supplementary measurements of&#xD;
      Standardized uptake values (SUV).&#xD;
&#xD;
      In case of agreement between the scans, the patient will proceed to clinical treatment as&#xD;
      usual. In case of disagreement between the three modalities a MRI will be performed on the&#xD;
      lesion of interest. If the results after MRI are still inconclusive a bone biopsy with&#xD;
      emphasis on getting marrow tissue as well as bone matrix, will be performed. This will in&#xD;
      many cases not be possible due to the size of the lesion and in these cases MRI will serve as&#xD;
      reference standard.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>N/A</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>Metastases to bone (yes/no)</measure>
    <time_frame>1 day (At the time of scan interpretation)</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">143</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Choline PET/CT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>18F-Choline PET/CT</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>18F-Choline PET/CT</intervention_name>
    <description>18F-Choline PET/CT</description>
    <arm_group_label>Choline PET/CT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed, histologically verified PCa and&#xD;
&#xD;
          -  Written consent and&#xD;
&#xD;
          -  PSA ≥ 20 ng/mL and/or&#xD;
&#xD;
          -  Gleason score &gt; 6 and/or&#xD;
&#xD;
          -  cT-stage ≥ cT2c&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Withdrawal of consent or&#xD;
&#xD;
          -  Other active malign disease&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Odense University Hospiatal</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>October 10, 2016</last_update_submitted>
  <last_update_submitted_qc>October 10, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Mike Allan Mortensen</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Prostate cancer</keyword>
  <keyword>Staging</keyword>
  <keyword>PET/CT</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>Choline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02232685
org study id: MAM_PROSTAGE1
nct id: NCT02232685
lead sponsor: 
has dmc: Yes
Prostate cancer is currently the leading newly diagnosed cancer in the industrialized world.
      Treatment of prostate cancer is highly dependent on the stage of the disease. Current methods
      for staging are known to be inaccurate. Prior studies from our department suggest that PET/CT
      is useful in staging of bone metastases in patients with prostate cancer. The aim of this
      study is to test the usefulness of Choline PET/CT for the staging of bone metastases compared
      to current standard methods in patients with newly diagnosed prostate cancer.

      Better initial staging will result in better treatment of the individual patient. If we are
      able to develop a more accurate method of staging patients with undetected metastases on
      current staging will be spared of the side-effects associated with current treatment -
      impotence, incontinence, radiation damage etc.
1. Introduction. Cancer of the prostate (PCa) is currently the leading newly diagnosed
           cancer and the second most common cause of cancer deaths among men in the industrialized
           world . In Denmark alone more than 4000 men are yearly diagnosed with PCa . As PCa
           primarily affects elderly patients, one can assume that PCa will become one of the most
           important medical issues in the developed world due to the already high incidence
           combined with a growing population of elderly men.

           The aetiology of the disease is not well understood. In its most common form PCa evolves
           from the glandular tissue of the prostate. Metastatic spread will most commonly happen
           as lymphogenous spread to the regional lymph nodes or as haematogenous spread to the red
           bone marrow .

           Intended curative treatment of PCa is associated with considerable side effects, in
           particular incontinence, impotence and radiation damage to the surrounding tissues.
           Furthermore, over 30% of patients with organ-confined disease, which was treated with
           radical prostatectomy, will have biochemical relapse within 10 years . Relapse may be
           due to local recurrent disease suggesting poor surgical quality or poor initial staging
           with undetected metastases at the time of treatment.

           At diagnosis patients are stratified as having low, intermediary or high risk of
           dissieminatio according to D'Amico. Patients with intermediate or high risk of
           dissemination will be examined further with whole-body bone scintigraphy (WBS) and
           pelvic lymph node dissection (PLND).

        2. Background. 2.1. Current staging and limitations. WBS has been the examination of choice
           for evaluation of potential dissemination to bone. WBS utilizes 99mTc-labeled methylene
           diphosphonate (99mTc-MDP) that binds to the bone matrix formed by the osteoblasts. Gamma
           cameras detect the γ-radiation emitted by the decaying tracer thereby creating a
           2-dimentional image depicting local osteoblast activity .

           Several limitations apply to the use of WBS in staging of patients with PCa. Sensitivity
           has reported as low as 39% in lesion-based analysis in patients with a low number of
           lesions . This combines with a low sensitivity due to many equivocal lesions caused by
           other bone pathology than metastasis.

           Sensitivity and specificity is improved by the use of single-photon emission computed
           tomography (SPECT), where the same tracer as with WBS is used to generate a
           three-dimensional image using a rotating gamma camera. This method also gives better
           anatomical information on the exact position of a potential metastasis.

           The examination of choice for the evaluation of potential metastases to lymph nodes is
           extended PLND . This procedure is done either prior to radiotherapy or during
           prostatectomy in patients with intermediate or high risk of dissemination. The optimal
           extent of the dissection is debated. The extended PLND performed at our institution
           includes the nodes in the obturator fossa, the nodes over the external iliac artery and
           vein, the nodes around the internal iliac artery and the nodes along the common iliac
           artery up to the crossing of the ureter. This dissection is assumed to include
           approximately 75% of lymph nodes known to harbor primary prostatic lymph node metastases
           . Extended PLND is surgically demanding with risk of lymphocele formation, infectious
           complications and severe bleeding due the lymph nodes' close proximity to the large
           vessels in the pelvis. All in all extended PLND is perhaps the best option for lymph
           node staging of PCa but it cannot be considered as optimal due to the above-mentioned
           issues.

           2.2 Positron Emission Tomography (PET). Positron Emission Tomography combined with
           Computerized Tomography (PET/CT) is a well-established tool in diagnosing and staging of
           several types of cancer . PET is an imaging technique where pairs of gamma rays emitted
           by positron-emitting radionuclide tracer are detected, producing a three-dimensional
           image of tracer concentration based on the amount of gamma rays emitted. The radioactive
           tracer is coupled to a biologically active molecule depending on the organ or metabolic
           process of interest . These images can then be fused with CT to create a combined
           functional and high-resolution anatomical image. Several tracers have been developed for
           use in cancer diagnostics and staging. As of now, PET/CT has no generally accepted role
           in the diagnosing or staging of PCa neither in Europe nor in the US .

           2.2.1 Choline. Choline is a precursor for phosphatidylcholine, a phospholipid that is
           integrated in the cell membrane making it a marker for cell membrane turnover and
           metabolism . 11C-Choline was first used as a PET tracer in 1997 . Since then many
           studies have been performed with 11C-Choline and later 18F-Choline (FCH) having
           approximately the same properties as 11C-Choline, but with a longer half-life (110 min
           vs. 20 min) making it more versatile in every-day use. A recent study from our
           department tested the use of FCH-PET/CT in detecting lymph node metastasis in 210
           patients with PCa . The study concluded that FCH-PET/CT was not ideally suited for lymph
           node staging but could give additional information about bone metastasis. Several other
           investigators have also implied this , . A likely reason for the better detection of
           metastasis to the bone is that bone metastasis in an early stage is actually bone-marrow
           metastases rather than bone matrix metastasis and that it most likely that bone-marrow
           metastases proceed to bone matrix metastases. These will not be detectable by WBS (and
           probably not by CT and MRI either). Larger prospective series on the use of FCH-PET/CT
           for imaging of bone metastasis in PCa-patients have not yet been produced.

        3. Trial objective. To compare the diagnostic accuracy in detecting bone metastases of WBS,
           SPECT and FCH PET/CT in 280 patients with newly diagnosed PCa with intermediate or high
           risk of disseminated disease

        4. Method. The patients will have two scans performed, first one with two acquisitions
           using only one administration of tracer i.e. a WBS followed by a SPECT acquisition and
           on another day a FCH-PET/CT. Image acquisition will be performed approximately 60 min
           after intravenous injection of the tracer.

      The scans are performed in random order within three weeks and the images interpreted by a
      specialist in nuclear medicine and a specialist in radiology. Patients who already have had
      WBS performed will only have a FCH-PET/CT performed.

      Images are interpreted based on visual evaluation with supplementary measurements of
      Standardized uptake values (SUV).

      In case of agreement between the scans, the patient will proceed to clinical treatment as
      usual. In case of disagreement between the three modalities a MRI will be performed on the
      lesion of interest. If the results after MRI are still inconclusive a bone biopsy with
      emphasis on getting marrow tissue as well as bone matrix, will be performed. This will in
      many cases not be possible due to the size of the lesion and in these cases MRI will serve as
      reference standard.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Metastases to bone (yes/no)
time frame: 1 day (At the time of scan interpretation)
arm group label: Choline PET/CT
arm group type: Experimental
description: 18F-Choline PET/CT
intervention type: Device
intervention name: 18F-Choline PET/CT
description: 18F-Choline PET/CT
arm group label: Choline PET/CT
criteria: 
gender: Male
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Odense University Hospital
investigator full name: Mike Allan Mortensen
investigator title: MD
mesh term: Prostatic Neoplasms
mesh term: Choline