<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/NCT02212548</url>
  </required_header>
  <id_info>
    <org_study_id>Hydrogel</org_study_id>
    <nct_id>NCT02212548</nct_id>
  </id_info>
  <brief_title>Prostate-Rectal Separation With PEG Hydrogel and Its Effect on Decreasing Rectal Dose</brief_title>
  <official_title>Prostate-Rectal Separation With PEG Hydrogel and Its Effect on Decreasing Rectal Dose</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal North Shore Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal North Shore Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I prospective study of 30 patients to determine whether PEG hydrogel&#xD;
      (SpaceOAR) reduces the dose of radiation delivered to the rectum during Image Guided&#xD;
      Intensity Modulated Radiotherapy (IG-IMRT) for prostate cancer, by increasing the space&#xD;
      between the prostate and the rectum.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who are referred to the Northern Sydney Cancer Centre for radiotherapy for treatment&#xD;
      of their prostate cancer will be screened at the initial consultation for suitability for&#xD;
      participation in the study. Following informed consent, those who agree to participate in the&#xD;
      study will undergo the following procedures. Blood tests will be performed to ensure normal&#xD;
      coagulation profile and renal function prior to any procedure. Under transrectal ultrasound&#xD;
      guidance, patients will have insertion of fiducial gold seeds into the prostate under&#xD;
      anaesthesia. While the patient is in theatre and under anaesthesia, the PEG hydrogel&#xD;
      (SpaceOAR) will be inserted by Dr Thomas Eade, who will be competent in the procedure. The&#xD;
      patient will be in the dorsal lithotomy position and prepared and draped. A transrectal&#xD;
      ultrasound (TRUS) will be used for alignment of the needle and to ensure safe delivery. The&#xD;
      hydrogel precursor and accelerator solutions will be mixed and connected to the Y connector&#xD;
      that has been flushed with saline and to a syringe holder that ensures both syringe barrels&#xD;
      are injected at the same time (comes with commercial product). The solutions will be injected&#xD;
      within 30 minutes of mixing. After aspirating to ensure the tip of the needle is not&#xD;
      intravascular, the perirectal space will be adequately dissected from the apex to midgland by&#xD;
      injecting saline into the space between denonvilliers fascia and the anterior rectal space&#xD;
      under TRUS guidance. This hydrodissection, prior to delivery of the hydrogel, should create a&#xD;
      distance of 3-4 mm between the prostate and the rectum. Maintaining the needle position and&#xD;
      angulation, the saline syringe is disconnected and the hydrogel system connected. After&#xD;
      aspirating to ensure the needle tip is not in a blood vessel and under TRUS guidance, the&#xD;
      hydrogel is injected in a smooth, continuous technique. The gel sets up within approximately&#xD;
      8 seconds.&#xD;
&#xD;
      In order to compare the effect of the PEG hydrogel (SpaceOAR) on the dose of radiation&#xD;
      received by the rectum, two radiotherapy plans will be created. One planning CT scan will&#xD;
      therefore be performed prior to the injection of the PEG hydrogel and one one week following&#xD;
      injection of the hydrogel. The two treatment plans will be created by the same radiation&#xD;
      therapist.&#xD;
&#xD;
      As the hydrogel is clearly visible on MRI and not on CT scans, we will obtain a pelvic MRI&#xD;
      scan following injection of the hydrogel.. The MRI scans will be used in planning and fused&#xD;
      to the planning CT scans to aid voluming.&#xD;
&#xD;
      Treatment:&#xD;
&#xD;
      Patients will undergo standard prostate cancer planning and treatment using image guided dose&#xD;
      escalated IMRT as per the RNSH Department protocol and guidelines to a dose of 80Gy in 40&#xD;
      fractions 14.&#xD;
&#xD;
      Rectal Dose Analysis:&#xD;
&#xD;
      Two plans with dose-volume histograms will be created, one using the planning CT scan from&#xD;
      prior to the PEG hydrogel (SpaceOAR) injection and one using the planning CT and MRI&#xD;
      performed one week post hydrogel injection. MRI scans will be obtained on the same day as the&#xD;
      CT simulation using the same bladder filling and rectal emptying protocols. Each patient will&#xD;
      have two plans created by the same Radiation Therapist. This will allow for comparison&#xD;
      between the 2 plans. The patient will be treated according to the post PEG hydrogel injection&#xD;
      plan, with the initial plan for comparison purposes only. The volume of rectum receiving&#xD;
      80Gy, 75Gy, 70Gy, 65Gy, 60Gy, 40Gy, 35Gy and 25Gy will be compared with the two plans.&#xD;
&#xD;
      Patient assessment:&#xD;
&#xD;
      Patients will be assessed immediately post injection of the hydrogel, 24hrs later by&#xD;
      telephone and 1 week later by telephone to determine if there has been any adverse event&#xD;
      related to the PEG hydrogel (SpaceOAR) injection. This will include questions regarding pain&#xD;
      or discomfort, infection, bleeding, and changes in bowel or bladder function. Information&#xD;
      about every adverse event will be collected and recorded on the appropriate case report form.&#xD;
      Adverse events will be described by duration (start and end dates), severity grade, and&#xD;
      action taken. A follow-up report will follow the initial report within 5 working days. Any&#xD;
      reports where the adverse event has not resolved at this time will be followed up to&#xD;
      resolution of the event or until it becomes chronic and a statement is made to this effect.&#xD;
&#xD;
      During radiotherapy treatment patients will be assessed weekly in the clinic and their&#xD;
      toxicity will be recorded using the modified RTOG and National Cancer Institute Common&#xD;
      Terminology Criteria (v4.0) for adverse events.&#xD;
&#xD;
      Patients will be reviewed in the clinic 3 months, 9 months, 15 months and 21 months post&#xD;
      completion of treatment and rectal toxicity will be assessed using the modified RTOG and&#xD;
      National Cancer Institute Common Terminology Criteria (v4.0) for adverse events.&#xD;
&#xD;
      Adverse events:&#xD;
&#xD;
      An adverse event is any undesirable experience associated with the use of a medical product&#xD;
      in a patient. All adverse events will be appropriately reported by duration (start and end&#xD;
      dates), severity grade, and action taken on the appropriate case report form.&#xD;
&#xD;
      Grade 1 or mild events are easily tolerated. Grade 2 or moderate events cause enough&#xD;
      discomfort to interfere with usual activity.&#xD;
&#xD;
      Grade 3 or severe events result in inability to carry out usual activities. Grade 4 events&#xD;
      are life threatening or disabling. The serious adverse event will be documented and medically&#xD;
      assessed by the investigator. As the PEG hydrogel cannot be removed following injection,&#xD;
      patients will be treated medically and symptomatically. A follow-up report will follow the&#xD;
      initial report within 5 working days. Any reports where the adverse event has not resolved at&#xD;
      this time will be followed up to resolution of the event or until it becomes chronic and a&#xD;
      statement is made to this effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2013</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>% volume of rectum receiving 40Gy, 65Gy, 70Gy, 75Gy and 80Gy</measure>
    <time_frame>CT scans taken 1-2 weeks apart (Pre and post Hydrogel insertion)</time_frame>
    <description>Estimated % volume of rectum as measured on CT dosimetry based on CT scans ore and post insertion of hydrogel taken 1-2 weeks apart (% volume of rectum receiving 40Gy, 65Gy, 70Gy, 75Gy and 80Gy).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of serious adverse events or complications secondary to PEG hydrogel insertion.</measure>
    <time_frame>Post-Hydrogel Insertion then 2nd weekly during radiation therapy up to 9 weeks and at a 3 month follow-up.</time_frame>
    <description>Physcian reported toxicity using CTC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal toxicity</measure>
    <time_frame>Second weekly evaluation during radiation therapy up to 9 weeks and at 3 mths, 9 mths, 15 mths, 21 mths, 27mths and 36mths post treatment.</time_frame>
    <description>Patients will be physician scored using the CTC and patient scored using the EPIC QOL questionaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Cancer of the Prostate</condition>
  <arm_group>
    <arm_group_label>Hydrogel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patient will be in the dorsal lithotomy position and prepared and draped. A transrectal ultrasound (TRUS) will be used for alignment of the needle and to ensure safe delivery. The hydrogel precursor and accelerator solutions will be mixed and connected to the Y connector that has been flushed with saline and to a syringe holder that ensures both syringe barrels are injected at the same time. After aspirating to ensure the tip of the needle is not intravascular, the perirectal space will be adequately dissected from the apex to midgland by injecting saline into the space between denonvilliers fascia and the anterior rectal space under TRUS guidance. Maintaining the needle position and angulation, the saline syringe is disconnected and the hydrogel system connected. After aspirating to ensure the needle tip is not in a blood vessel and under TRUS guidance, the 'PEG Hydrogel (SpaceOAR) is injected in a smooth, continuous technique.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PEG Hydrogel (SpaceOAR)</intervention_name>
    <description>A single injection of PEG hydrogel (SpaceOAR) through the perineum under transrectal ultrasound guidance while under general anaesthetic.</description>
    <arm_group_label>Hydrogel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Prostate cancer, confirmed with histopathology specimen;&#xD;
&#xD;
          2. Eligible for prostate radiotherapy, either for definitive treatment or to aid local&#xD;
             control in patients with known metastatic disease.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Metastatic disease where local radiotherapy is not recommended management&#xD;
&#xD;
          2. Complications following prostate biopsy including infection&#xD;
&#xD;
          3. Urinary retention symptoms&#xD;
&#xD;
          4. Bleeding disorder&#xD;
&#xD;
          5. Renal impairment&#xD;
&#xD;
          6. Anal fistula or perianal abscess&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Eade, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal North Shore Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northern Sydney Cancer Centre, Royal North Shore Hospital</name>
      <address>
        <city>St. Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <results_reference>
    <citation>Juneja P, Kneebone A, Booth JT, Thwaites DI, Kaur R, Colvill E, Ng JA, Keall PJ, Eade T. Prostate motion during radiotherapy of prostate cancer patients with and without application of a hydrogel spacer: a comparative study. Radiat Oncol. 2015 Oct 24;10:215. doi: 10.1186/s13014-015-0526-1.</citation>
    <PMID>26499473</PMID>
  </results_reference>
  <results_reference>
    <citation>van Gysen K, Kneebone A, Alfieri F, Guo L, Eade T. Feasibility of and rectal dosimetry improvement with the use of SpaceOAR(R) hydrogel for dose-escalated prostate cancer radiotherapy. J Med Imaging Radiat Oncol. 2014 Aug;58(4):511-6. doi: 10.1111/1754-9485.12152. Epub 2014 Mar 3.</citation>
    <PMID>24580893</PMID>
  </results_reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Royal North Shore Hospital</investigator_affiliation>
    <investigator_full_name>Professor Thomas Eade</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>SpaceOAR Hydrogel Image Guided Modulated Radiotherapy</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>Yes</sharing_ipd>
    <ipd_description>Other centres with ethics approval to use annonymised data</ipd_description>
  </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/NCT02212548
org study id: Hydrogel
nct id: NCT02212548
lead sponsor: 
has dmc: Yes
This is a Phase I prospective study of 30 patients to determine whether PEG hydrogel
      (SpaceOAR) reduces the dose of radiation delivered to the rectum during Image Guided
      Intensity Modulated Radiotherapy (IG-IMRT) for prostate cancer, by increasing the space
      between the prostate and the rectum.
Patients who are referred to the Northern Sydney Cancer Centre for radiotherapy for treatment
      of their prostate cancer will be screened at the initial consultation for suitability for
      participation in the study. Following informed consent, those who agree to participate in the
      study will undergo the following procedures. Blood tests will be performed to ensure normal
      coagulation profile and renal function prior to any procedure. Under transrectal ultrasound
      guidance, patients will have insertion of fiducial gold seeds into the prostate under
      anaesthesia. While the patient is in theatre and under anaesthesia, the PEG hydrogel
      (SpaceOAR) will be inserted by Dr Thomas Eade, who will be competent in the procedure. The
      patient will be in the dorsal lithotomy position and prepared and draped. A transrectal
      ultrasound (TRUS) will be used for alignment of the needle and to ensure safe delivery. The
      hydrogel precursor and accelerator solutions will be mixed and connected to the Y connector
      that has been flushed with saline and to a syringe holder that ensures both syringe barrels
      are injected at the same time (comes with commercial product). The solutions will be injected
      within 30 minutes of mixing. After aspirating to ensure the tip of the needle is not
      intravascular, the perirectal space will be adequately dissected from the apex to midgland by
      injecting saline into the space between denonvilliers fascia and the anterior rectal space
      under TRUS guidance. This hydrodissection, prior to delivery of the hydrogel, should create a
      distance of 3-4 mm between the prostate and the rectum. Maintaining the needle position and
      angulation, the saline syringe is disconnected and the hydrogel system connected. After
      aspirating to ensure the needle tip is not in a blood vessel and under TRUS guidance, the
      hydrogel is injected in a smooth, continuous technique. The gel sets up within approximately
      8 seconds.

      In order to compare the effect of the PEG hydrogel (SpaceOAR) on the dose of radiation
      received by the rectum, two radiotherapy plans will be created. One planning CT scan will
      therefore be performed prior to the injection of the PEG hydrogel and one one week following
      injection of the hydrogel. The two treatment plans will be created by the same radiation
      therapist.

      As the hydrogel is clearly visible on MRI and not on CT scans, we will obtain a pelvic MRI
      scan following injection of the hydrogel.. The MRI scans will be used in planning and fused
      to the planning CT scans to aid voluming.

      Treatment:

      Patients will undergo standard prostate cancer planning and treatment using image guided dose
      escalated IMRT as per the RNSH Department protocol and guidelines to a dose of 80Gy in 40
      fractions 14.

      Rectal Dose Analysis:

      Two plans with dose-volume histograms will be created, one using the planning CT scan from
      prior to the PEG hydrogel (SpaceOAR) injection and one using the planning CT and MRI
      performed one week post hydrogel injection. MRI scans will be obtained on the same day as the
      CT simulation using the same bladder filling and rectal emptying protocols. Each patient will
      have two plans created by the same Radiation Therapist. This will allow for comparison
      between the 2 plans. The patient will be treated according to the post PEG hydrogel injection
      plan, with the initial plan for comparison purposes only. The volume of rectum receiving
      80Gy, 75Gy, 70Gy, 65Gy, 60Gy, 40Gy, 35Gy and 25Gy will be compared with the two plans.

      Patient assessment:

      Patients will be assessed immediately post injection of the hydrogel, 24hrs later by
      telephone and 1 week later by telephone to determine if there has been any adverse event
      related to the PEG hydrogel (SpaceOAR) injection. This will include questions regarding pain
      or discomfort, infection, bleeding, and changes in bowel or bladder function. Information
      about every adverse event will be collected and recorded on the appropriate case report form.
      Adverse events will be described by duration (start and end dates), severity grade, and
      action taken. A follow-up report will follow the initial report within 5 working days. Any
      reports where the adverse event has not resolved at this time will be followed up to
      resolution of the event or until it becomes chronic and a statement is made to this effect.

      During radiotherapy treatment patients will be assessed weekly in the clinic and their
      toxicity will be recorded using the modified RTOG and National Cancer Institute Common
      Terminology Criteria (v4.0) for adverse events.

      Patients will be reviewed in the clinic 3 months, 9 months, 15 months and 21 months post
      completion of treatment and rectal toxicity will be assessed using the modified RTOG and
      National Cancer Institute Common Terminology Criteria (v4.0) for adverse events.

      Adverse events:

      An adverse event is any undesirable experience associated with the use of a medical product
      in a patient. All adverse events will be appropriately reported by duration (start and end
      dates), severity grade, and action taken on the appropriate case report form.

      Grade 1 or mild events are easily tolerated. Grade 2 or moderate events cause enough
      discomfort to interfere with usual activity.

      Grade 3 or severe events result in inability to carry out usual activities. Grade 4 events
      are life threatening or disabling. The serious adverse event will be documented and medically
      assessed by the investigator. As the PEG hydrogel cannot be removed following injection,
      patients will be treated medically and symptomatically. A follow-up report will follow the
      initial report within 5 working days. Any reports where the adverse event has not resolved at
      this time will be followed up to resolution of the event or until it becomes chronic and a
      statement is made to this effect.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: % volume of rectum receiving 40Gy, 65Gy, 70Gy, 75Gy and 80Gy
time frame: CT scans taken 1-2 weeks apart (Pre and post Hydrogel insertion)
description: Estimated % volume of rectum as measured on CT dosimetry based on CT scans ore and post insertion of hydrogel taken 1-2 weeks apart (% volume of rectum receiving 40Gy, 65Gy, 70Gy, 75Gy and 80Gy).
measure: Evaluation of serious adverse events or complications secondary to PEG hydrogel insertion.
time frame: Post-Hydrogel Insertion then 2nd weekly during radiation therapy up to 9 weeks and at a 3 month follow-up.
description: Physcian reported toxicity using CTC
measure: Gastrointestinal toxicity
time frame: Second weekly evaluation during radiation therapy up to 9 weeks and at 3 mths, 9 mths, 15 mths, 21 mths, 27mths and 36mths post treatment.
description: Patients will be physician scored using the CTC and patient scored using the EPIC QOL questionaire
arm group label: Hydrogel
arm group type: Experimental
description: The patient will be in the dorsal lithotomy position and prepared and draped. A transrectal ultrasound (TRUS) will be used for alignment of the needle and to ensure safe delivery. The hydrogel precursor and accelerator solutions will be mixed and connected to the Y connector that has been flushed with saline and to a syringe holder that ensures both syringe barrels are injected at the same time. After aspirating to ensure the tip of the needle is not intravascular, the perirectal space will be adequately dissected from the apex to midgland by injecting saline into the space between denonvilliers fascia and the anterior rectal space under TRUS guidance. Maintaining the needle position and angulation, the saline syringe is disconnected and the hydrogel system connected. After aspirating to ensure the needle tip is not in a blood vessel and under TRUS guidance, the 'PEG Hydrogel (SpaceOAR) is injected in a smooth, continuous technique.
intervention type: Device
intervention name: PEG Hydrogel (SpaceOAR)
description: A single injection of PEG hydrogel (SpaceOAR) through the perineum under transrectal ultrasound guidance while under general anaesthetic.
arm group label: Hydrogel
criteria: 
gender: Male
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Thomas Eade, MD
role: Principal Investigator
affiliation: Royal North Shore Hospital
facility: 
country: Australia
citation: Juneja P, Kneebone A, Booth JT, Thwaites DI, Kaur R, Colvill E, Ng JA, Keall PJ, Eade T. Prostate motion during radiotherapy of prostate cancer patients with and without application of a hydrogel spacer: a comparative study. Radiat Oncol. 2015 Oct 24;10:215. doi: 10.1186/s13014-015-0526-1.
PMID: 26499473
citation: van Gysen K, Kneebone A, Alfieri F, Guo L, Eade T. Feasibility of and rectal dosimetry improvement with the use of SpaceOAR(R) hydrogel for dose-escalated prostate cancer radiotherapy. J Med Imaging Radiat Oncol. 2014 Aug;58(4):511-6. doi: 10.1111/1754-9485.12152. Epub 2014 Mar 3.
PMID: 24580893
responsible party type: Principal Investigator
investigator affiliation: Royal North Shore Hospital
investigator full name: Professor Thomas Eade
investigator title: Dr.
mesh term: Prostatic Neoplasms
sharing ipd: Yes
ipd description: Other centres with ethics approval to use annonymised data