<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/NCT03246802</url>
  </required_header>
  <id_info>
    <org_study_id>H17-01641</org_study_id>
    <nct_id>NCT03246802</nct_id>
  </id_info>
  <brief_title>Partial Prostate Salvage High Dose Rate Brachytherapy</brief_title>
  <acronym>SalvageHDR</acronym>
  <official_title>High Dose Rate Partial Prostate Brachytherapy as Salvage Treatment for Local Failures After Previous External Beam Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British Columbia Cancer Agency</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>British Columbia Cancer Agency</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A dose-response relationship for radiation in the management of prostate cancer is well&#xD;
      established. Local recurrence of prostate cancer after external beam radiotherapy occurs in&#xD;
      at least 40% of patients treated because of inability to deliver sufficient dose through&#xD;
      external beam techniques. These patients respond well to re-irradiation using brachytherapy&#xD;
      with about 50% of selected patients remaining free of recurrence 5 years after salvage.&#xD;
      Advanced imaging using multiparametric Magnetic Resonance Imaging (mpMRI) allows&#xD;
      identification of the site of recurrence, permitting partial prostate salvage brachytherapy.&#xD;
      There is extensive literature on Low Dose Rate salvage brachytherapy but less on High Dose&#xD;
      Rate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Appropriately selected patients with histologically documented recurrence 3 years or more&#xD;
      after initial external beam radiotherapy will undergo mpMRI for identification of the site of&#xD;
      recurrence. A planning transrectal ultrasound (TRUS) will be obtained for fusion with the&#xD;
      mpMRI and transposition of the target volume (GTV=gross tumor volume). A margin of 4.5 cm&#xD;
      will be added to the GTV to create a focal planning target volume (PTV). The margin may be&#xD;
      cropped at the interface with critical organs. Two fractions of HDR brachytherapy will be&#xD;
      delivered, each from a single implant, 2 weeks apart. Following treatment patients will be&#xD;
      monitored for toxicity and quality of life using the Expanded Prostate cancer Index (EPIC)&#xD;
      questionnaire as well as the International Prostate Symptom score. Efficacy will be evaluated&#xD;
      by monitoring the Prostate Specific Antigen (PSA) and repeat mpMRI at 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>
    <intervention_model_description>High Dose Rate brachytherapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Late adverse gastrointestinal or genitourinary events grade 3 or higher</measure>
    <time_frame>3-60 months</time_frame>
    <description>Common Terminology Criteria for Adverse Events (CTCAE V4.0)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Late Quality of Life</measure>
    <time_frame>3-60 months</time_frame>
    <description>Expanded Prostate Cancer Index (EPIC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late lower urinary tract symptoms</measure>
    <time_frame>3-60 months</time_frame>
    <description>International Prostate Symptom Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute grade 3 or higher gastrointestinal or genitourinary adverse events</measure>
    <time_frame>0-3 months</time_frame>
    <description>Common Terminology Criteria for Adverse Events (CTCAE V4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Quality of Life changes</measure>
    <time_frame>0-3 months</time_frame>
    <description>Expanded Prostate Cancer Index (EPIC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute lower urinary symptoms</measure>
    <time_frame>0-3 months</time_frame>
    <description>International Prostate Symptoms Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical disease free survival</measure>
    <time_frame>60 months</time_frame>
    <description>PSA &lt; 0.4 ng/ml at 60 months</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Recurrent Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>HDR partial prostate brachytherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 fractions of high dose rate prostate brachytherapy will be delivered to the site of recurrent disease as determined by mp-MRI</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>HDR partial prostate brachytherapy</intervention_name>
    <description>temporary radioactive implant</description>
    <arm_group_label>HDR partial prostate brachytherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;45 and Life expectancy &gt;10 years&#xD;
&#xD;
          -  Previous External Beam Radiotherapy (EBRT) dose up to 78Gray/39 fractions, 81 Gray/45&#xD;
             fractions or 70 Gray/28 fractions&#xD;
&#xD;
          -  &gt; 3 year interval since EBRT&#xD;
&#xD;
          -  No late toxicity from prior EBRT &gt; grade 2&#xD;
&#xD;
          -  Rising PSA post EBRT &gt; nadir + 2 ng/ml but &lt; 10 ng/ml&#xD;
&#xD;
          -  PSA Doubling time &gt; 6 months&#xD;
&#xD;
          -  Negative staging with CT scan of the abdomen/pelvis and bone scan&#xD;
&#xD;
          -  Able to undergo multiparametric MRI with endorectal coil&#xD;
&#xD;
          -  Radiographic evidence of dominant intraprostatic lesion (DIL) as only area of&#xD;
             recurrence (i.e unifocal recurrence) and corresponding to site of original disease&#xD;
&#xD;
          -  Biopsy confirmation of DIL with pathology review by British Columbia Cancer Agency&#xD;
             GenitoUrinary pathologist (TB)&#xD;
&#xD;
          -  Willing to provide informed consent&#xD;
&#xD;
          -  History and physical examination within 90 days of registration&#xD;
&#xD;
          -  ECOG performance status 0-1 prior to registration&#xD;
&#xD;
          -  IPSS &lt; 16, or adequate voiding study (post void residual &lt; 100cc and peak flow rate &gt;&#xD;
             10 cc/second).&#xD;
&#xD;
          -  No prior trans urethral prostatic resection&#xD;
&#xD;
          -  Recurrence suitable for implant with HDR brachytherapy as assessed on ultrasound&#xD;
             simulation (maximum PTV ideally &lt; 65% of prostate volume)&#xD;
&#xD;
          -  No history of inflammatory bowel disease or previous rectal surgery&#xD;
&#xD;
          -  Suitable for procedure under anesthesia, spinal or general&#xD;
&#xD;
          -  INR &lt;2.5 and platelet count &gt;75 x 109/L&#xD;
&#xD;
          -  Androgen Deprivation Therapy may be initiated at the discretion of the treating&#xD;
             oncologist&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not compliant with criteria above&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mira Keyes, MD</last_name>
    <role>Study Director</role>
    <affiliation>BCCA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Juanita Crook, MD</last_name>
    <phone>2507123958</phone>
    <email>jcrook@bccancer.bc.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Francois Bachand, MD</last_name>
    <phone>2507123900</phone>
    <email>fbachand@bccancer.bc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BCCA Center for the Southern Interior</name>
      <address>
        <city>Kelowna</city>
        <state>British Columbia</state>
        <zip>V1Y 5L3</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juanita Crook, MD</last_name>
      <phone>250 712 3958</phone>
      <email>jcrook@bccancer.bc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Francois Bachand, MD</last_name>
      <phone>250 712 3900</phone>
      <email>fbachand@bccancer.bc.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Juanita Crook, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Deidre Batchelar, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michelle Hilts, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marie-Pierre Milette, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ross Halperin, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David Petrik, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David Kim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brenda Farnquist, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Terry Bainbridge, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Arrayeh E, Westphalen AC, Kurhanewicz J, Roach M 3rd, Jung AJ, Carroll PR, Coakley FV. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e787-93. doi: 10.1016/j.ijrobp.2011.11.030. Epub 2012 Feb 11.</citation>
    <PMID>22331003</PMID>
  </reference>
  <reference>
    <citation>Banerjee R, Park SJ, Anderson E, Demanes DJ, Wang J, Kamrava M. From whole gland to hemigland to ultra-focal high-dose-rate prostate brachytherapy: A dosimetric analysis. Brachytherapy. 2015 May-Jun;14(3):366-72. doi: 10.1016/j.brachy.2014.12.007. Epub 2015 Feb 10.</citation>
    <PMID>25680768</PMID>
  </reference>
  <reference>
    <citation>Crook J, Ots A, Gaztanaga M, Schmid M, Araujo C, Hilts M, Batchelar D, Parker B, Bachand F, Milette MP. Ultrasound-planned high-dose-rate prostate brachytherapy: dose painting to the dominant intraprostatic lesion. Brachytherapy. 2014 Sep-Oct;13(5):433-41. doi: 10.1016/j.brachy.2014.05.006. Epub 2014 Jun 20.</citation>
    <PMID>24958556</PMID>
  </reference>
  <reference>
    <citation>Da Rosa MR, Milot L, Sugar L, Vesprini D, Chung H, Loblaw A, Pond GR, Klotz L, Haider MA. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging. 2015 Jan;41(1):220-5. doi: 10.1002/jmri.24710. Epub 2014 Jul 21.</citation>
    <PMID>25044935</PMID>
  </reference>
  <reference>
    <citation>Mason J, Al-Qaisieh B, Bownes P, Thwaites D, Henry A. Dosimetry modeling for focal high-dose-rate prostate brachytherapy. Brachytherapy. 2014 Nov-Dec;13(6):611-7. doi: 10.1016/j.brachy.2014.06.007. Epub 2014 Jul 29.</citation>
    <PMID>25085456</PMID>
  </reference>
  <reference>
    <citation>Rose JN, Crook JM, Pickles T, Keyes M, Morris WJ. Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity. Brachytherapy. 2015 May-Jun;14(3):342-9. doi: 10.1016/j.brachy.2015.01.002. Epub 2015 Feb 26.</citation>
    <PMID>25727178</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>June 29, 2021</last_update_submitted>
  <last_update_submitted_qc>June 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>British Columbia Cancer Agency</investigator_affiliation>
    <investigator_full_name>Juanita Crook</investigator_full_name>
    <investigator_title>Professor of Radiation Oncology</investigator_title>
  </responsible_party>
  <keyword>recurrent prostate cancer</keyword>
  <keyword>mpMRI</keyword>
  <keyword>salvage HDR brachytherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03246802
org study id: H17-01641
nct id: NCT03246802
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A dose-response relationship for radiation in the management of prostate cancer is well
      established. Local recurrence of prostate cancer after external beam radiotherapy occurs in
      at least 40% of patients treated because of inability to deliver sufficient dose through
      external beam techniques. These patients respond well to re-irradiation using brachytherapy
      with about 50% of selected patients remaining free of recurrence 5 years after salvage.
      Advanced imaging using multiparametric Magnetic Resonance Imaging (mpMRI) allows
      identification of the site of recurrence, permitting partial prostate salvage brachytherapy.
      There is extensive literature on Low Dose Rate salvage brachytherapy but less on High Dose
      Rate.
Appropriately selected patients with histologically documented recurrence 3 years or more
      after initial external beam radiotherapy will undergo mpMRI for identification of the site of
      recurrence. A planning transrectal ultrasound (TRUS) will be obtained for fusion with the
      mpMRI and transposition of the target volume (GTV=gross tumor volume). A margin of 4.5 cm
      will be added to the GTV to create a focal planning target volume (PTV). The margin may be
      cropped at the interface with critical organs. Two fractions of HDR brachytherapy will be
      delivered, each from a single implant, 2 weeks apart. Following treatment patients will be
      monitored for toxicity and quality of life using the Expanded Prostate cancer Index (EPIC)
      questionnaire as well as the International Prostate Symptom score. Efficacy will be evaluated
      by monitoring the Prostate Specific Antigen (PSA) and repeat mpMRI at 2 years.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: High Dose Rate brachytherapy
primary purpose: Treatment
masking: None (Open Label)
measure: Late adverse gastrointestinal or genitourinary events grade 3 or higher
time frame: 3-60 months
description: Common Terminology Criteria for Adverse Events (CTCAE V4.0)
measure: Late Quality of Life
time frame: 3-60 months
description: Expanded Prostate Cancer Index (EPIC)
measure: Late lower urinary tract symptoms
time frame: 3-60 months
description: International Prostate Symptom Score
measure: Acute grade 3 or higher gastrointestinal or genitourinary adverse events
time frame: 0-3 months
description: Common Terminology Criteria for Adverse Events (CTCAE V4.0)
measure: Acute Quality of Life changes
time frame: 0-3 months
description: Expanded Prostate Cancer Index (EPIC)
measure: Acute lower urinary symptoms
time frame: 0-3 months
description: International Prostate Symptoms Score
measure: Biochemical disease free survival
time frame: 60 months
description: PSA < 0.4 ng/ml at 60 months
arm group label: HDR partial prostate brachytherapy
arm group type: Experimental
description: 2 fractions of high dose rate prostate brachytherapy will be delivered to the site of recurrent disease as determined by mp-MRI
intervention type: Radiation
intervention name: HDR partial prostate brachytherapy
description: temporary radioactive implant
arm group label: HDR partial prostate brachytherapy
criteria: 
gender: Male
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: No
last name: Mira Keyes, MD
role: Study Director
affiliation: BCCA
last name: Juanita Crook, MD
phone: 2507123958
email: jcrook@bccancer.bc.ca
last name: Francois Bachand, MD
phone: 2507123900
email: fbachand@bccancer.bc.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
citation: Arrayeh E, Westphalen AC, Kurhanewicz J, Roach M 3rd, Jung AJ, Carroll PR, Coakley FV. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e787-93. doi: 10.1016/j.ijrobp.2011.11.030. Epub 2012 Feb 11.
PMID: 22331003
citation: Banerjee R, Park SJ, Anderson E, Demanes DJ, Wang J, Kamrava M. From whole gland to hemigland to ultra-focal high-dose-rate prostate brachytherapy: A dosimetric analysis. Brachytherapy. 2015 May-Jun;14(3):366-72. doi: 10.1016/j.brachy.2014.12.007. Epub 2015 Feb 10.
PMID: 25680768
citation: Crook J, Ots A, Gaztanaga M, Schmid M, Araujo C, Hilts M, Batchelar D, Parker B, Bachand F, Milette MP. Ultrasound-planned high-dose-rate prostate brachytherapy: dose painting to the dominant intraprostatic lesion. Brachytherapy. 2014 Sep-Oct;13(5):433-41. doi: 10.1016/j.brachy.2014.05.006. Epub 2014 Jun 20.
PMID: 24958556
citation: Da Rosa MR, Milot L, Sugar L, Vesprini D, Chung H, Loblaw A, Pond GR, Klotz L, Haider MA. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging. 2015 Jan;41(1):220-5. doi: 10.1002/jmri.24710. Epub 2014 Jul 21.
PMID: 25044935
citation: Mason J, Al-Qaisieh B, Bownes P, Thwaites D, Henry A. Dosimetry modeling for focal high-dose-rate prostate brachytherapy. Brachytherapy. 2014 Nov-Dec;13(6):611-7. doi: 10.1016/j.brachy.2014.06.007. Epub 2014 Jul 29.
PMID: 25085456
citation: Rose JN, Crook JM, Pickles T, Keyes M, Morris WJ. Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity. Brachytherapy. 2015 May-Jun;14(3):342-9. doi: 10.1016/j.brachy.2015.01.002. Epub 2015 Feb 26.
PMID: 25727178
responsible party type: Principal Investigator
investigator affiliation: British Columbia Cancer Agency
investigator full name: Juanita Crook
investigator title: Professor of Radiation Oncology
mesh term: Prostatic Neoplasms
sharing ipd: No