<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/NCT03294889</url>
  </required_header>
  <id_info>
    <org_study_id>2017-01236</org_study_id>
    <nct_id>NCT03294889</nct_id>
  </id_info>
  <brief_title>ONE-SHOT Trial - Ultra-hypofractionated Single-dose SBRT for Prostate Cancer</brief_title>
  <official_title>ONE-SHOT - Single Shot Radiotherapy for Localized Prostate Cancer. A Multicenter, Single Arm, Phase I/II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Geneva</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Humanitas Hospital, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kantonsspital Graubünden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Geneva</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>
      The main objective of the phase I/II trial is to determine the safety and efficacy of a&#xD;
      single fraction SBRT at a dose of 19 Gy in patients with localized prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total dose and dose per fraction play an important role in the curative treatment of prostate&#xD;
      cancer with radiotherapy (RT). Modern image guided external RT allows safe dose escalation of&#xD;
      prostate cancer. There are strong radiobiological and clinical considerations that suggest&#xD;
      that treatment with a small number of large fractions (hypofractionation) may increase the&#xD;
      therapeutic ratio of RT for prostate cancer by increasing the tumor cell killing effect with&#xD;
      relatively less toxic effect on the surrounding late responding normal tissues compared to&#xD;
      conventional fractionation.&#xD;
&#xD;
      The question of how far can the number of fractions with SBRT be reduced is an exciting&#xD;
      research matter with an undoubtful goal, face the challenge of assessing the potential for&#xD;
      cure of prostate cancer patients with a single and unique fraction of high dose irradiation&#xD;
      similar to what is already undertaken with radiosurgery against brain, lung, and liver&#xD;
      targets.&#xD;
&#xD;
      We hypothesize that an ultra-hypofractionated single-dose SBRT employing state of the art of&#xD;
      image-guided RT techniques may be feasible, with a safe toxicity profile and an optimal&#xD;
      long-term tumor control. Hence, a prospective phase I/II clinical trial will be initiated in&#xD;
      prostate cancer patients with a localized disease to validate this treatment schedule as an&#xD;
      alternative to normofractionated/moderate hypofractionated RT schedules to be tested in a&#xD;
      second time in a phase III trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Clinical performance</measure>
    <time_frame>3 months</time_frame>
    <description>Toxicity will be evaluated using Grade ≥ 3 genitourinary and/or gastrointestinal acute adverse event (AE) during the first 3 month according to CTCAE classification v.4.03 (Phase I).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>The primary endpoint is 3-years biochemical relapse free survival (bRFS). bRFS and its 97.5% one-sided confidence interval (CI) will be determined using the Kaplan Meier method. If the expected value of 96% isn't included in this interval, the efficacy of the experimental treatment will be questioned. (Phase II).</description>
  </primary_outcome>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Prostate Cancer</condition>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic body radition (SBRT)</intervention_name>
    <description>Ultra-hypofractionated single-fraction SBRT with urethra-sparing with image-guidance and intra-fractional control motion with the Calypso® system.&#xD;
19 Gy in a single fraction to the whole prostate gland ± proximal seminal vesicles&#xD;
17 Gy in a single fraction to the urethra planning-risk volume (PRV)</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent according to ICH/GCP regulations before registration and&#xD;
             prior to any trial specific procedures&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the prostate without small cell features&#xD;
&#xD;
          -  Tumor clinical stage cT1c-2c, pN0 or cN0, M0, according to UICC TNM 2009&#xD;
&#xD;
          -  MRI staging must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b&#xD;
             or T2c&#xD;
&#xD;
          -  Gleason score at biopsy 3+3 or 3+4 (WHO 2016 Grade Groups 1, 2)&#xD;
&#xD;
          -  PSA ≤15 ng/ml&#xD;
&#xD;
          -  WHO performance status 0-1&#xD;
&#xD;
          -  International Prostate Symptom Score ≤ 10 (alpha blockers allowed)&#xD;
&#xD;
          -  MRI-based volume estimation of prostate gland ≤ 70 cc&#xD;
&#xD;
          -  Patient agrees not to father a child during trial treatment and during 6 months&#xD;
             thereafter&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tumor clinical stage cT3a-3b or T4&#xD;
&#xD;
          -  Evidence of T3a, T3b or T4 disease as assessed by MRI&#xD;
&#xD;
          -  Positive lymph-nodes or metastatic disease from prostate cancer on imaging studies.&#xD;
&#xD;
          -  Significant tumor on the transitional zone as assessed by MRI&#xD;
&#xD;
          -  Gleason at biopsy ≥ 4+3&#xD;
&#xD;
          -  Androgen deprivation therapy or products known to affect PSA levels&#xD;
&#xD;
          -  Impossibility to implant Calypso beacons&#xD;
&#xD;
          -  History of hematologic or primary solid tumor malignancy, unless in remission for at&#xD;
             least 3 years from registration with the exception of curatively treated localized&#xD;
             non-melanoma skin cancer&#xD;
&#xD;
          -  Prior pelvic radiotherapy&#xD;
&#xD;
          -  Previous surgery for prostate cancer&#xD;
&#xD;
          -  Previous transurethral resection of the prostate (TURP) (&lt; 12 weeks before&#xD;
             registration)&#xD;
&#xD;
          -  Hip prosthesis&#xD;
&#xD;
          -  Severe or active co-morbidity likely to impact on the advisability of SBRT&#xD;
&#xD;
          -  Any other serious underlying medical, psychiatric, psychological, familial or&#xD;
             geographical condition, which in the judgment of the investigator may interfere with&#xD;
             the planned staging, treatment and follow-up, affect patient compliance or place the&#xD;
             patient at high risk from treatment-related complications&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Histologically confirmed adenocarcinoma of the prostate</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Zilli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Geneva</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas Zilli, MD</last_name>
    <phone>+41 79 55 32 563</phone>
    <email>Thomas.Zilli@hcuge.ch</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laurence Zulianello, PhD</last_name>
    <phone>+ 22 372 72 05</phone>
    <email>laurence.zulianello@hcuge.ch</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital of Geneva</name>
      <address>
        <city>Genève</city>
        <zip>1205</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Zilli, MD</last_name>
      <phone>+41 79 55 32 563</phone>
      <email>thomas.zilli@hcuge.ch</email>
    </contact>
    <contact_backup>
      <last_name>Laurence Zulianello, PhD</last_name>
      <phone>+ 41 22 372 7205</phone>
      <email>laurence.zulianello@hcuge.ch</email>
    </contact_backup>
    <investigator>
      <last_name>Giorgio Lamana, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yves Chalandon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>May 13, 2020</last_update_submitted>
  <last_update_submitted_qc>May 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Thomas Zilli</investigator_full_name>
    <investigator_title>Médecin Adjoint Agrégé</investigator_title>
  </responsible_party>
  <keyword>Prostate cancer</keyword>
  <keyword>Stereotactic body radiation therapy</keyword>
  <keyword>Calypso® beacon system</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/NCT03294889
org study id: 2017-01236
nct id: NCT03294889
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main objective of the phase I/II trial is to determine the safety and efficacy of a
      single fraction SBRT at a dose of 19 Gy in patients with localized prostate cancer.
Total dose and dose per fraction play an important role in the curative treatment of prostate
      cancer with radiotherapy (RT). Modern image guided external RT allows safe dose escalation of
      prostate cancer. There are strong radiobiological and clinical considerations that suggest
      that treatment with a small number of large fractions (hypofractionation) may increase the
      therapeutic ratio of RT for prostate cancer by increasing the tumor cell killing effect with
      relatively less toxic effect on the surrounding late responding normal tissues compared to
      conventional fractionation.

      The question of how far can the number of fractions with SBRT be reduced is an exciting
      research matter with an undoubtful goal, face the challenge of assessing the potential for
      cure of prostate cancer patients with a single and unique fraction of high dose irradiation
      similar to what is already undertaken with radiosurgery against brain, lung, and liver
      targets.

      We hypothesize that an ultra-hypofractionated single-dose SBRT employing state of the art of
      image-guided RT techniques may be feasible, with a safe toxicity profile and an optimal
      long-term tumor control. Hence, a prospective phase I/II clinical trial will be initiated in
      prostate cancer patients with a localized disease to validate this treatment schedule as an
      alternative to normofractionated/moderate hypofractionated RT schedules to be tested in a
      second time in a phase III trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical performance
time frame: 3 months
description: Toxicity will be evaluated using Grade ≥ 3 genitourinary and/or gastrointestinal acute adverse event (AE) during the first 3 month according to CTCAE classification v.4.03 (Phase I).
measure: Progression free survival (PFS)
time frame: 3 years
description: The primary endpoint is 3-years biochemical relapse free survival (bRFS). bRFS and its 97.5% one-sided confidence interval (CI) will be determined using the Kaplan Meier method. If the expected value of 96% isn't included in this interval, the efficacy of the experimental treatment will be questioned. (Phase II).
intervention type: Radiation
intervention name: Stereotactic body radition (SBRT)
description: Ultra-hypofractionated single-fraction SBRT with urethra-sparing with image-guidance and intra-fractional control motion with the Calypso® system.
19 Gy in a single fraction to the whole prostate gland ± proximal seminal vesicles
17 Gy in a single fraction to the urethra planning-risk volume (PRV)
criteria: 
gender: Male
gender based: Yes
gender description: Histologically confirmed adenocarcinoma of the prostate
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Thomas Zilli, MD
role: Principal Investigator
affiliation: University Hospital, Geneva
last name: Thomas Zilli, MD
phone: +41 79 55 32 563
email: Thomas.Zilli@hcuge.ch
last name: Laurence Zulianello, PhD
phone: + 22 372 72 05
email: laurence.zulianello@hcuge.ch
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Thomas Zilli
investigator title: Médecin Adjoint Agrégé
mesh term: Prostatic Neoplasms
sharing ipd: No