<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/NCT04503772</url>
  </required_header>
  <id_info>
    <org_study_id>2020-A00403-36</org_study_id>
    <secondary_id>20.06.16-36701</secondary_id>
    <nct_id>NCT04503772</nct_id>
  </id_info>
  <brief_title>Preoperative Stereotactic Radiosurgery for Brain Metastases</brief_title>
  <acronym>STEP</acronym>
  <official_title>Phase II Study to Assess Preoperative Hypofractionated Stereotactic Radiotherapy of Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Jean Perrin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Groupement Interrégional de Recherche Clinique et d'Innovation (AURA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Jean Perrin</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>
      STEP is a French multicentre, prospective, non-randomized, phase II study designed to assess&#xD;
      6-months local control after pre-operative stereotactic radiosurgery (SRS) for patients with&#xD;
      brain metastases&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 4, 2021</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>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>Evaluation of 6-months local control rate after preoperative SRS</measure>
    <time_frame>6 months after preoperative SRS (M6)</time_frame>
    <description>Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of 1-year local control rate after preoperative SRS</measure>
    <time_frame>12 months after preoperative SRS (M12)</time_frame>
    <description>Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of 1-year radionecrosis rate after preoperative SRS</measure>
    <time_frame>12 months after preoperative SRS (M12)</time_frame>
    <description>Radionecrosis is defined either histologically post-operatively according to the anatomopathological report or in the absence of salvage surgery by the appearance or increase of gadolinium contrast on T1 MRI sequences associated with an increase in the cerebral brain volume (CBV) ratio (brain blood volume of the tumour / brain blood volume of the non-tumour white matter) of less than 2 on perfusion MRI sequences and/or a standard uptake volume (SUV max) of less than 1, 59 on positron emission tomography (PET) scanners at 6-fluoro-[18 fluoro]-L-dihydroxyphenylalanine (F-DOPA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of overall survival</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS)</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade ≥ 3 will be considered &quot;severe&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of leptomeningeal relapses</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>According to cerebral MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of cerebral distant control</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>Follow by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of predictive factors for local brain control, complication and prognosis factors for survival</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of cognitive function</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>Mini-mental state examination (MMSE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of quality of life</measure>
    <time_frame>At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)</time_frame>
    <description>European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>Experimental arm (all patients)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive preoperative hypofractionated stereotactic radiosurgery (SRS).&#xD;
According to the association of french-speaking neuro-oncologists (ANOCEF) recommendations, total dose and fractionation will be 33 Gy in 3 fractions at the isocenter, 23.1 Gy in envelope (70% isodose), i.e. 30 Gy in growth tumor volume (GTV) envelope.) Surgery will take place within 3 days of the preoperative SRS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Preoperative SRS</intervention_name>
    <description>Patient will be treat with preoperative SRS and then surgery for brain metastases is realized within 3 days.</description>
    <arm_group_label>Experimental arm (all patients)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≤ 4 distinct brain metastases, one with surgical indication&#xD;
&#xD;
          -  Diagnosis of primary histologically proven breast, digestive or non-small cells lung&#xD;
             cancer&#xD;
&#xD;
          -  ≤ 5 cm larger diameter&#xD;
&#xD;
          -  Karnofsky performance status ≥ 70&#xD;
&#xD;
          -  No contraindication for MRI&#xD;
&#xD;
          -  Possibility for the patient to be treat with both surgery and stereotactic&#xD;
             radiotherapy&#xD;
&#xD;
          -  ≥ 18 years old&#xD;
&#xD;
          -  Estimated overall survival ≥ 6 months according to diagnosis specific - graded&#xD;
             prognostic assessment (DS GPA)&#xD;
&#xD;
          -  Written inform consent signed&#xD;
&#xD;
          -  Affiliation to the French social security system&#xD;
&#xD;
          -  For women of childbearing age including those on luteinizing hormone-releasing hormone&#xD;
             (LH-RH) agonists for ovarian suppression: inclusion negative serum pregnancy test (≤ 7&#xD;
             days prior to the start of preoperative stereotactic radiosurgery (SRS).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lymphoma, leukaemia, multiple myeloma, germinal tumours or cerebral primary cancer&#xD;
&#xD;
          -  Metastases from small-cells lung cancer, kidney cancer, melanoma or sarcoma&#xD;
&#xD;
          -  Mass effect with deflection ≥ 5 mm from median line or hydrocephaly or compression 4th&#xD;
             ventricle, patient neurologically unstable, need for emergency decompressive surgery&#xD;
&#xD;
          -  &gt; 4 brain metastases&#xD;
&#xD;
          -  Contraindication to anaesthesia, MRI or gadolinium injection&#xD;
&#xD;
          -  Proximity of the tumour with organs at risk which do not allow the prescribed dose to&#xD;
             be reached in the envelope&#xD;
&#xD;
          -  Pregnant or breastfeeding woman&#xD;
&#xD;
          -  Anti vascular endothelial growth factor (VEGF) within 6 weeks before treatment&#xD;
&#xD;
          -  Documented leptomeningeal injury&#xD;
&#xD;
          -  History of irradiation of the encephalon in toto&#xD;
&#xD;
          -  History of stereotactic radiotherapy on metastasis to be operated on&#xD;
&#xD;
          -  Non-candidate patient for surgery&#xD;
&#xD;
          -  Surgical delay &gt; 3 days compared to stereotactic radiotherapy&#xD;
&#xD;
          -  Estimated survival &lt; 6 months by DS GPA&#xD;
&#xD;
          -  Patient under guardianship or curators&#xD;
&#xD;
          -  Psychological disorder (cognitive disorders, mental alertness, etc.) or social&#xD;
             (deprivation of liberty by judicial or administrative decision) or geographical&#xD;
             reasons that may compromise medical monitoring of the trial or compliance with&#xD;
             treatment&#xD;
&#xD;
          -  Woman of childbearing age without effective contraception&#xD;
&#xD;
          -  Patient participating in another intervention study within 4 weeks prior to inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lucie BRUN, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Jean Perrin</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Angeline GINZAC COUVÉ, PhD</last_name>
    <phone>0463663337</phone>
    <phone_ext>+33</phone_ext>
    <email>angeline.ginzac@clermont.unicancer.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Centre Jean PERRIN</name>
      <address>
        <city>Clermont-Ferrand</city>
        <state>Puy-de-Dôme</state>
        <zip>63800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucie BRUN, MD</last_name>
      <email>lucie.brun@clermont.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Julian BIAU, MD, PhD</last_name>
      <email>julian.biau@clermont.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Julian BIAU, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lucie BRUN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Juliette MOREAU, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jessica MIROIR, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble Alpes</name>
      <address>
        <city>Grenoble</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andréa DESAGNEAUX, MD</last_name>
    </contact>
    <investigator>
      <last_name>Andréa DESAGNEAUX, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69002</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne d'Hombres, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anne d'Hombres, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon BÉRARD</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Coralie MONCHARMONT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Coralie MONCHARMONT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier d'Annecy-Genevois</name>
      <address>
        <city>Metz-Tessy</city>
        <zip>74370</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexandre TESSIER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Alexandre TESSIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest</name>
      <address>
        <city>Saint-Herblain</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François THYLLAYS, MD</last_name>
    </contact>
    <investigator>
      <last_name>François THYLLAIS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de cancérologie de la Loire Lucien Neuwirth</name>
      <address>
        <city>Saint-Priest-en-Jarez</city>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicolas MAGNÉ, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Nicolas MAGNÉ, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de cancérologie Strasbourg Europe (ICANS)</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clara LEFEVRE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Clara LEFEVRE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>https://pubmed.ncbi.nlm.nih.gov/34320940/</url>
    <description>Study protocol article</description>
  </link>
  <reference>
    <citation>Ginzac A, Dupic G, Brun L, Molnar I, Casile M, Durando X, Verrelle P, Lemaire JJ, Khalil T, Biau J. Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial. BMC Cancer. 2021 Jul 28;21(1):864. doi: 10.1186/s12885-021-08602-0.</citation>
    <PMID>34320940</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>brain metastases</keyword>
  <keyword>preoperative stereotactic radiosurgery</keyword>
  <keyword>local control</keyword>
  <keyword>radionecrosis</keyword>
  <keyword>overall survival</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain 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/NCT04503772
org study id: 2020-A00403-36
secondary id: 20.06.16-36701
nct id: NCT04503772
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
STEP is a French multicentre, prospective, non-randomized, phase II study designed to assess
      6-months local control after pre-operative stereotactic radiosurgery (SRS) for patients with
      brain metastases
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of 6-months local control rate after preoperative SRS
time frame: 6 months after preoperative SRS (M6)
description: Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
measure: Evaluation of 1-year local control rate after preoperative SRS
time frame: 12 months after preoperative SRS (M12)
description: Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria.
measure: Evaluation of 1-year radionecrosis rate after preoperative SRS
time frame: 12 months after preoperative SRS (M12)
description: Radionecrosis is defined either histologically post-operatively according to the anatomopathological report or in the absence of salvage surgery by the appearance or increase of gadolinium contrast on T1 MRI sequences associated with an increase in the cerebral brain volume (CBV) ratio (brain blood volume of the tumour / brain blood volume of the non-tumour white matter) of less than 2 on perfusion MRI sequences and/or a standard uptake volume (SUV max) of less than 1, 59 on positron emission tomography (PET) scanners at 6-fluoro-[18 fluoro]-L-dihydroxyphenylalanine (F-DOPA)
measure: Evaluation of overall survival
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause.
measure: Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS)
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade ≥ 3 will be considered "severe".
measure: Rate of leptomeningeal relapses
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: According to cerebral MRI
measure: Evaluation of cerebral distant control
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: Follow by MRI
measure: Determination of predictive factors for local brain control, complication and prognosis factors for survival
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
measure: Evaluation of cognitive function
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: Mini-mental state examination (MMSE)
measure: Evaluation of quality of life
time frame: At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
description: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)
arm group label: Experimental arm (all patients)
arm group type: Experimental
description: Patients will receive preoperative hypofractionated stereotactic radiosurgery (SRS).
According to the association of french-speaking neuro-oncologists (ANOCEF) recommendations, total dose and fractionation will be 33 Gy in 3 fractions at the isocenter, 23.1 Gy in envelope (70% isodose), i.e. 30 Gy in growth tumor volume (GTV) envelope.) Surgery will take place within 3 days of the preoperative SRS.
intervention type: Procedure
intervention name: Preoperative SRS
description: Patient will be treat with preoperative SRS and then surgery for brain metastases is realized within 3 days.
arm group label: Experimental arm (all patients)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lucie BRUN, MD
role: Principal Investigator
affiliation: Centre Jean Perrin
last name: Angeline GINZAC COUVÉ, PhD
phone: 0463663337
phone ext: +33
email: angeline.ginzac@clermont.unicancer.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
url: https://pubmed.ncbi.nlm.nih.gov/34320940/
description: Study protocol article
citation: Ginzac A, Dupic G, Brun L, Molnar I, Casile M, Durando X, Verrelle P, Lemaire JJ, Khalil T, Biau J. Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial. BMC Cancer. 2021 Jul 28;21(1):864. doi: 10.1186/s12885-021-08602-0.
PMID: 34320940
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No