<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/NCT02976402</url>
  </required_header>
  <id_info>
    <org_study_id>SHARP</org_study_id>
    <nct_id>NCT02976402</nct_id>
  </id_info>
  <brief_title>Stereotactic Hypofractionated Accelerated Radiotherapy Post-Prostatectomy</brief_title>
  <acronym>SHARP</acronym>
  <official_title>Stereotactic Hypofractionated Accelerated Radiotherapy Post-Prostatectomy: a Phase I Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacao Champalimaud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacao Champalimaud</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present phase I trial evaluates the feasibility of a postoperative stereotactic&#xD;
      hypofractionated external beam radiation therapy delivered in patients who underwent radical&#xD;
      prostatectomy with adverse pathological features or early biochemical failure. Modern&#xD;
      computer-driven technology enables the implementation of ultra-high hypofractionated&#xD;
      Image-Guided Radiotherapy (IGRT) safely.&#xD;
&#xD;
      Eligible patients for this study are those with:&#xD;
&#xD;
        -  Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical&#xD;
           prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically&#xD;
           assisted; there is no time limit for the date of radical prostatectomy)&#xD;
&#xD;
        -  Pathologic (p)T3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle&#xD;
           involvement&#xD;
&#xD;
        -  Undetectable post-radical prostatectomy PSA that becomes detectable and then increases&#xD;
           on 2 subsequent measurements (PSA of &gt; 0.1 - ≤ 2.0 ng/mL)&#xD;
&#xD;
        -  Life expectancy: 10 years&#xD;
&#xD;
        -  ECOG performance status of 0 -1&#xD;
&#xD;
        -  No distant metastases, based on the following workup within 60 days prior to&#xD;
           registration&#xD;
&#xD;
        -  Magnetic resonance imaging (MRI) of the pelvis&#xD;
&#xD;
        -  PSMA/Choline Positron Emission Tomography (PET) to exclude systemic disease in patients&#xD;
           with biochemical recurrence&#xD;
&#xD;
        -  Patients can be on androgen deprivation therapy&#xD;
&#xD;
        -  Ability to understand and willingness to sign a study-specific informed consent prior to&#xD;
           study.&#xD;
&#xD;
      Patients enrolled in the study will undergo image-guided, volumetric intensity-modulated arc&#xD;
      radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance&#xD;
      procedures with emphasis on normal tissue sparing and delivery accuracy via the use of&#xD;
      devices that ensure stability and beam location reproducibility.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The present study evaluates the feasibility of postoperative stereotactic hypofractionated&#xD;
      external beam radiation therapy delivered in patients who underwent radical prostatectomy&#xD;
      with adverse pathological features or early biochemical failure. Regardless the two settings&#xD;
      (adjuvant or salvage), external beam radiation therapy for prostate cancer is usually a&#xD;
      protracted course, since a total dose of 66 Gy to 70 Gy is needed to be effective. At the&#xD;
      typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 treatments over the&#xD;
      course of 7 weeks to complete, which is very costly and extremely time consuming. On the&#xD;
      other hand, the α/β ratio for prostate cancer has estimated to be as low as 1.5 Gy,&#xD;
      significantly lower than the 3 Gy value estimated for late complications.Therefore, the&#xD;
      delivery of the same equivalent total dose at 2 Gy/fraction (normalized total dose) to the&#xD;
      prostate using a hypofractionation regimen, a part from the practical benefits of reducing&#xD;
      the treatment cost and number of sessions for patients to radiotherapy departments, should&#xD;
      have a sparing effect on early responding normal tissues through the reduction in the total&#xD;
      dose delivered, as well as a reduction in the incidence of late complications. Trials&#xD;
      investigating clinical and toxicity outcomes of moderate hypofractionation schedules in the&#xD;
      curative setting have reached sufficient follow-up to show similar efficacy and toxicity to&#xD;
      conventionally fractionated regimens.&#xD;
&#xD;
      Stereotactic body radiation therapy, or SBRT, is on the shortest end of the hypofractionation&#xD;
      spectrum. It is accomplished in a five treatments. With its pinpoint accuracy, many&#xD;
      Institutions currently use it for primary treatment at doses up to 9 Gy per treatment,&#xD;
      leading to excellent outcomes at least at early time points.Patients enrolled in the study&#xD;
      will undergo image-guided, volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with&#xD;
      state-of-the-art treatment-planning and quality assurance procedures with emphasis on normal&#xD;
      tissue sparing and delivery accuracy via the use of devices that ensure stability and beam&#xD;
      location reproducibility.A rectal balloon with air filling will be used for anatomical&#xD;
      reproducibility, while a urethral catheter loaded with beacon transponders will be used to&#xD;
      ensure set-up reproducibility and online target tracking. Previously untreated patients who&#xD;
      underwent radical prostatectomy with adverse pathologic findings will be enrolled in a phase&#xD;
      I study, consisting of 31 Gy (5 fractions of 6.2 Gy), respectively, delivered over a 1-week&#xD;
      period at 5 fractions per week. This dosage corresponds to 68.2 Gy (for an α/βratio estimate&#xD;
      of 1.5 Gy), compared to 52.7 Gy (for an α/β estimate of 4 Gy) in a conventional schedule. In&#xD;
      those who developed early biochemical failure the radiation schedule will consists in 32.5 Gy&#xD;
      (5 fractions of 6.5 Gy), respectively, delivered over a 1-week period at 5 fractions per&#xD;
      week. This dosage corresponds to 74.3 Gy (for an α/β ratio estimate of 1.5 Gy), compared to&#xD;
      56.9 Gy (for an α/β estimate of 4 Gy) in a conventional schedule.&#xD;
&#xD;
      Patients will be followed at one month post-treatment and every 3 months for up to 12 months&#xD;
      (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will&#xD;
      focus, though not exclusively, on urinary, rectal and sexual functions and will be assessed&#xD;
      through validated EPIC questionnaires. Serum PSA values will be drawn on the same schedule as&#xD;
      clinical follow-up. The study will be continuously monitored for a minimum of 5 years. In the&#xD;
      event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment&#xD;
      regimens, the trial will be terminated according to the standard stopping rules: &gt;3/first 10,&#xD;
      and &gt;5/first 25 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">November 2022</completion_date>
  <primary_completion_date type="Anticipated">November 2022</primary_completion_date>
  <phase>Phase 1</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>Feasibility (ability to deliver radiation treatment as planned).</measure>
    <time_frame>Participants should be followed continuously, for the duration of 5 years</time_frame>
    <description>Monitoring treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with acute (≤ 90 days from treatment completion)treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Participants should be followed continuously, for the duration of 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with late (&gt; 90 days from treatment completion) treatment-related adverse events as assessed by CTCAE v4.0 with SBRT administered to the prostate bed</measure>
    <time_frame>Participants should be followed continuously, for the duration of 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with post-treatment quality of life impairment assessed through validated tools (EPIC)</measure>
    <time_frame>Participants should be followed continuously, for the duration of 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with post-treatment abnormal laboratory values (PSA relapse)</measure>
    <time_frame>Participants should be followed continuously, for the duration of 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Prostate Cancer Adenocarcinoma</condition>
  <condition>Adjuvant Radiotherapy</condition>
  <condition>Salvage Radiotherapy</condition>
  <condition>SBRT</condition>
  <condition>IGRT</condition>
  <condition>Urethral Sparing</condition>
  <arm_group>
    <arm_group_label>SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Postoperative RT consisting in:&#xD;
31 Gy in 5 sessions each of 6.2 Gy (adjuvant intent) delivered in one week&#xD;
32.5 Gy in 5 sessions each of 6.5 Gy (salvage intent) delivered in one week</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>Postoperative RT consisting in:&#xD;
31 Gy in 5 sessions each of 6.2 Gy (adjuvant intent) delivered in one week&#xD;
32.5 Gy in 5 sessions each of 6.5 Gy (salvage intent) delivered in one week</description>
    <arm_group_label>SBRT</arm_group_label>
    <other_name>Extremely Hypofractionationated Postoperative Radiotherapy for Prostate Cancer</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical&#xD;
             prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically&#xD;
             assisted; there is no time limit for the date of radical prostatectomy)&#xD;
&#xD;
          -  Pathologic (p)T3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle&#xD;
             involvement&#xD;
&#xD;
          -  Undetectable post-radical prostatectomy PSA that becomes detectable and then increases&#xD;
             on 2 subsequent measurements (PSA of &gt; 0.1 - ≤ 2.0 ng/mL)&#xD;
&#xD;
          -  Life expectancy: 10 years&#xD;
&#xD;
          -  ECOG performance status of 0 -1&#xD;
&#xD;
          -  No distant metastases, based on the following workup within 60 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Magnetic resonance imaging (MRI) of the pelvis&#xD;
&#xD;
          -  PSMA/Choline Positron Emission Tomography (PET) to exclude systemic disease in&#xD;
             patients with biochemical recurrence&#xD;
&#xD;
          -  Patients can be on androgen deprivation therapy&#xD;
&#xD;
          -  Ability to understand and willingness to sign a study-specific informed consent prior&#xD;
             to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  N1 patients are ineligible, as are those with lymph node (LN) enlargement &gt; 1.5 cm by&#xD;
             computed tomography (CT) or MRI of the pelvis, unless the LN is biopsy proven to be&#xD;
             negative.&#xD;
&#xD;
          -  Gross residual disease in the prostate fossa based on imaging evidence, unless biopsy&#xD;
             proven not to contain cancer.&#xD;
&#xD;
          -  Prior radiation of any kind to the prostate gland or pelvis&#xD;
&#xD;
          -  Prior brachytherapy is not allowed&#xD;
&#xD;
          -  History of inflammatory colitis or other active severe comorbidities&#xD;
&#xD;
          -  Patients who are on immunosuppressant medication&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlo Greco, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Champalimaud Foundation</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Manuela Seixas</last_name>
    <phone>+351 965289072</phone>
    <email>manuela.seixas@fundacaochampalimaud.pt</email>
  </overall_contact>
  <location>
    <facility>
      <name>Champalimaud Foundation</name>
      <address>
        <city>Lisboa</city>
        <zip>1400-038</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Seixas</last_name>
      <phone>+351 9675289072</phone>
    </contact>
  </location>
  <location_countries>
    <country>Portugal</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>July 22, 2019</last_update_submitted>
  <last_update_submitted_qc>July 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fundacao Champalimaud</investigator_affiliation>
    <investigator_full_name>Carlo Greco, MD</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_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/NCT02976402
org study id: SHARP
nct id: NCT02976402
lead sponsor: 
has dmc: No
The present phase I trial evaluates the feasibility of a postoperative stereotactic
      hypofractionated external beam radiation therapy delivered in patients who underwent radical
      prostatectomy with adverse pathological features or early biochemical failure. Modern
      computer-driven technology enables the implementation of ultra-high hypofractionated
      Image-Guided Radiotherapy (IGRT) safely.

      Eligible patients for this study are those with:

        -  Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical
           prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically
           assisted; there is no time limit for the date of radical prostatectomy)

        -  Pathologic (p)T3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle
           involvement

        -  Undetectable post-radical prostatectomy PSA that becomes detectable and then increases
           on 2 subsequent measurements (PSA of > 0.1 - ≤ 2.0 ng/mL)

        -  Life expectancy: 10 years

        -  ECOG performance status of 0 -1

        -  No distant metastases, based on the following workup within 60 days prior to
           registration

        -  Magnetic resonance imaging (MRI) of the pelvis

        -  PSMA/Choline Positron Emission Tomography (PET) to exclude systemic disease in patients
           with biochemical recurrence

        -  Patients can be on androgen deprivation therapy

        -  Ability to understand and willingness to sign a study-specific informed consent prior to
           study.

      Patients enrolled in the study will undergo image-guided, volumetric intensity-modulated arc
      radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance
      procedures with emphasis on normal tissue sparing and delivery accuracy via the use of
      devices that ensure stability and beam location reproducibility.
The present study evaluates the feasibility of postoperative stereotactic hypofractionated
      external beam radiation therapy delivered in patients who underwent radical prostatectomy
      with adverse pathological features or early biochemical failure. Regardless the two settings
      (adjuvant or salvage), external beam radiation therapy for prostate cancer is usually a
      protracted course, since a total dose of 66 Gy to 70 Gy is needed to be effective. At the
      typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 treatments over the
      course of 7 weeks to complete, which is very costly and extremely time consuming. On the
      other hand, the α/β ratio for prostate cancer has estimated to be as low as 1.5 Gy,
      significantly lower than the 3 Gy value estimated for late complications.Therefore, the
      delivery of the same equivalent total dose at 2 Gy/fraction (normalized total dose) to the
      prostate using a hypofractionation regimen, a part from the practical benefits of reducing
      the treatment cost and number of sessions for patients to radiotherapy departments, should
      have a sparing effect on early responding normal tissues through the reduction in the total
      dose delivered, as well as a reduction in the incidence of late complications. Trials
      investigating clinical and toxicity outcomes of moderate hypofractionation schedules in the
      curative setting have reached sufficient follow-up to show similar efficacy and toxicity to
      conventionally fractionated regimens.

      Stereotactic body radiation therapy, or SBRT, is on the shortest end of the hypofractionation
      spectrum. It is accomplished in a five treatments. With its pinpoint accuracy, many
      Institutions currently use it for primary treatment at doses up to 9 Gy per treatment,
      leading to excellent outcomes at least at early time points.Patients enrolled in the study
      will undergo image-guided, volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with
      state-of-the-art treatment-planning and quality assurance procedures with emphasis on normal
      tissue sparing and delivery accuracy via the use of devices that ensure stability and beam
      location reproducibility.A rectal balloon with air filling will be used for anatomical
      reproducibility, while a urethral catheter loaded with beacon transponders will be used to
      ensure set-up reproducibility and online target tracking. Previously untreated patients who
      underwent radical prostatectomy with adverse pathologic findings will be enrolled in a phase
      I study, consisting of 31 Gy (5 fractions of 6.2 Gy), respectively, delivered over a 1-week
      period at 5 fractions per week. This dosage corresponds to 68.2 Gy (for an α/βratio estimate
      of 1.5 Gy), compared to 52.7 Gy (for an α/β estimate of 4 Gy) in a conventional schedule. In
      those who developed early biochemical failure the radiation schedule will consists in 32.5 Gy
      (5 fractions of 6.5 Gy), respectively, delivered over a 1-week period at 5 fractions per
      week. This dosage corresponds to 74.3 Gy (for an α/β ratio estimate of 1.5 Gy), compared to
      56.9 Gy (for an α/β estimate of 4 Gy) in a conventional schedule.

      Patients will be followed at one month post-treatment and every 3 months for up to 12 months
      (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will
      focus, though not exclusively, on urinary, rectal and sexual functions and will be assessed
      through validated EPIC questionnaires. Serum PSA values will be drawn on the same schedule as
      clinical follow-up. The study will be continuously monitored for a minimum of 5 years. In the
      event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment
      regimens, the trial will be terminated according to the standard stopping rules: >3/first 10,
      and >5/first 25 patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility (ability to deliver radiation treatment as planned).
time frame: Participants should be followed continuously, for the duration of 5 years
description: Monitoring treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0
measure: Number of participants with acute (≤ 90 days from treatment completion)treatment-related adverse events as assessed by CTCAE v4.0
time frame: Participants should be followed continuously, for the duration of 5 years
measure: Number of participants with late (> 90 days from treatment completion) treatment-related adverse events as assessed by CTCAE v4.0 with SBRT administered to the prostate bed
time frame: Participants should be followed continuously, for the duration of 5 years
measure: Number of participants with post-treatment quality of life impairment assessed through validated tools (EPIC)
time frame: Participants should be followed continuously, for the duration of 5 years
measure: Number of participants with post-treatment abnormal laboratory values (PSA relapse)
time frame: Participants should be followed continuously, for the duration of 5 years
arm group label: SBRT
arm group type: Experimental
description: Postoperative RT consisting in:
31 Gy in 5 sessions each of 6.2 Gy (adjuvant intent) delivered in one week
32.5 Gy in 5 sessions each of 6.5 Gy (salvage intent) delivered in one week
intervention type: Radiation
intervention name: SBRT
description: Postoperative RT consisting in:
31 Gy in 5 sessions each of 6.2 Gy (adjuvant intent) delivered in one week
32.5 Gy in 5 sessions each of 6.5 Gy (salvage intent) delivered in one week
arm group label: SBRT
other name: Extremely Hypofractionationated Postoperative Radiotherapy for Prostate Cancer
criteria: 
gender: Male
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Carlo Greco, M.D.
role: Principal Investigator
affiliation: Champalimaud Foundation
last name: Manuela Seixas
phone: +351 965289072
email: manuela.seixas@fundacaochampalimaud.pt
facility: 
status: Recruiting
contact: 
country: Portugal
responsible party type: Principal Investigator
investigator affiliation: Fundacao Champalimaud
investigator full name: Carlo Greco, MD
investigator title: M.D.
mesh term: Adenocarcinoma