xml: <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/NCT05974475</url>
    </required_header>
    <id_info>
      <org_study_id>R1842/23-IEO1973</org_study_id>
      <nct_id>NCT05974475</nct_id>
    </id_info>
    <brief_title>MONDRIAN: Multi-omics Integrative Modelling for Stereotactic Body Radiotherapy in Early-stage Non-small Cell Lung Cancer</brief_title>
    <acronym>MONDRIAN</acronym>
    <official_title>MONDRIAN: Multi-omics Integrative Modelling for Stereotactic Body Radiotherapy in Early-stage Non-small Cell Lung Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>European Institute of Oncology</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Associazione Italiana per la Ricerca sul Cancro</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>European Institute of Oncology</source>
    <oversight_info>
      <has_dmc>No</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>
        Stereotactic Body Radiotherapy (SBRT) is a form of high-precision radiotherapy playing a&#xD;
        major role in patients diagnosed with early-stage non-small cell lung cancer (NSLCL),&#xD;
        especially when surgery cannot be performed. It is a non-invasive, well-tolerated treatment,&#xD;
        with an excellent ability to control disease recurrence. However, in some patients, disease&#xD;
        response is suboptimal: understanding why this happens may open doors to more aggressive&#xD;
        approaches, such as the combination with systemic therapies.&#xD;
  &#xD;
        Hence, the goal of this observational trial is to understand which clinical, imaging, and&#xD;
        biological factors are associated with response to SBRT through the development of complex&#xD;
        models. In other words, the main question it aims to answer is: &quot;Will this patient respond to&#xD;
        radiation treatment based on the characteristics of their disease?&quot;.&#xD;
  &#xD;
        Participants will be treated according to the best clinical practice standards, in agreement&#xD;
        with international, national, and internal guidelines.&#xD;
  &#xD;
        Researchers will compare data collected from patients treated with SBRT with those collected&#xD;
        from a similar group of patients, who will be treated with surgery, to see which factors are&#xD;
        actual predictors of response to SBRT, or rather are indicators of more or less aggressive&#xD;
        disease behavior.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The overall planned duration of the study is 60 months.&#xD;
  &#xD;
        The project is structured into five main tasks, as following:&#xD;
  &#xD;
          -  Task 1_Clinical study: Routine clinical data will be collected from eligible patients,&#xD;
             including demographics, disease and treatment characteristics, pulmonary function, and&#xD;
             blood count parameters.&#xD;
  &#xD;
          -  Task 2_Radiomics study: Quantitative imaging analysis will be performed on both&#xD;
             diagnostic computed tomographies (CTs) and positron emission tomographies (PETs). A&#xD;
             software compliant with the Imaging Biomarker Standardization Initiative (IBSI) will be&#xD;
             used to extract radiomic features at baseline and at the first clinical progression (or&#xD;
             at the last available follow-up, whichever comes first). Clinically established&#xD;
             qualitative and semiquantitative metrics (e.g. pleural effusion in CT images and&#xD;
             standardized uptake value in PET images) will be retrieved, as well.&#xD;
  &#xD;
          -  Task 3_Gene expression study: Gene expression profiling will be performed at baseline in&#xD;
             both cohorts to investigate the presence of a prognostic pretreatment signature. The&#xD;
             analysis will be performed on formalin-fixed paraffin-embedded (FFPE) tissue samples&#xD;
             (namely, resected tumor in the surgical cohort and bioptic sample- whenever available-&#xD;
             in the SBRT group). A next-generation sequencing (NGS)-based assay which targets 395&#xD;
             immune-related genes and named as Oncomine™ Immune Response Research Assay, will be&#xD;
             employed.&#xD;
  &#xD;
          -  Task 4_Proteomics study: Proteomics will integrate the study of RNA expression performed&#xD;
             in Task 3. As in Task 3, the analysis will be performed on FFPE samples, from both&#xD;
             patients' cohorts.&#xD;
  &#xD;
          -  Task 5_Integrative model building: Integration of all previous features in a unique&#xD;
             classification model able to determine a precise estimate of individuals with high vs&#xD;
             low risk of disease progression and, at the same time, identify relevant predictive&#xD;
             factors. The proposed classification model will integrate data from different sources&#xD;
             using a multi-layer deep neural network. Federated learning techniques will also be used&#xD;
             to reduce the bias due to the choice of a specific trial or data source.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2028</completion_date>
    <primary_completion_date type="Anticipated">September 2026</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>24 Months</target_duration>
    <primary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>24 months</time_frame>
      <description>The time between the beginning of SBRT or date of surgery, and any disease progression (local, regional, distant), death from any cause, or last follow-up, whichever comes first.</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">270</enrollment>
    <condition>Lung Neoplasm Malignant</condition>
    <arm_group>
      <arm_group_label>SBRT Cohort</arm_group_label>
      <description>Radiation: Stereotactic Body Radiotherapy (SBRT)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Surgery Cohort</arm_group_label>
      <description>Procedure: Surgery</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>SBRT</intervention_name>
      <description>State-of-art SBRT will be delivered in 3-5 fractions; prescription doses and fractionation schedules will be defined according to patient- and tumor-related characteristics (e.g. pulmonary comorbidities, tumor location: peripheral vs central vs ultra-central).</description>
      <arm_group_label>SBRT Cohort</arm_group_label>
      <other_name>Stereotactic body radiotherapy</other_name>
      <other_name>Stereotactic Ablative Radiotherapy (SABR)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Surgery</intervention_name>
      <description>State-of-art surgery will be consist in pulmonary anatomical resection (i.e. segmentectomy or lobectomy) and systematic lymph node dissection.</description>
      <arm_group_label>Surgery Cohort</arm_group_label>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Formalin-fixed paraffin-embedded (FFPE) bioptic samples (SBRT cohort); formalin-fixed&#xD;
        paraffin-embedded (FFPE) surgical specimens (surgical cohort)&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Tertiary care cancer center, early-stage NSCLC.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histologically proven NSCLC; all histologies will be considered eligible (e.g.&#xD;
               squamous, adenocarcinoma, large cell carcinoma);&#xD;
  &#xD;
            -  American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) classification&#xD;
               (8th Edition) clinical stage I-II;&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1;&#xD;
  &#xD;
            -  No absolute contraindications to either surgery (e.g. severe comorbidities) or SBRT&#xD;
               (e.g. active connective diseases, severe pulmonary fibrosis);&#xD;
  &#xD;
            -  Ability and willingness to sign a written informed consent for treatment and study&#xD;
               participation.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior diagnosis of invasive cancer (within 3 years before the diagnosis of ES-NSCLC);&#xD;
  &#xD;
            -  Mental diseases or psychiatric disorders preventing the acquisition of a valid&#xD;
               informed consent.&#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>Stefania Volpe, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Istituto Europeo di Oncologia IRCCS</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Stefania Volpe, MD</last_name>
      <phone>+390257489037</phone>
      <email>stefania.volpe@ieo.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Cristiana Fodor, MSc</last_name>
      <phone>+390257489037</phone>
      <email>cristiana.fodor@ieo.it</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Istituto Europeo di Oncologia IRCCS</name>
        <address>
          <city>Milano</city>
          <state>MI</state>
          <zip>20141</zip>
          <country>Italy</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Early stage non-small cell lung cancer</keyword>
    <keyword>Stereotactic body radiotherapy (SBRT)</keyword>
    <keyword>Radiosensitivity</keyword>
    <keyword>Radioresistance</keyword>
    <keyword>Multi-omics</keyword>
    <keyword>Radiomics</keyword>
    <keyword>Genomics</keyword>
    <keyword>Proteomics</keyword>
    <keyword>Outcome modeling</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05974475
  org study id: R1842/23-IEO1973
  nct id: NCT05974475
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Stereotactic Body Radiotherapy (SBRT) is a form of high-precision radiotherapy playing a
        major role in patients diagnosed with early-stage non-small cell lung cancer (NSLCL),
        especially when surgery cannot be performed. It is a non-invasive, well-tolerated treatment,
        with an excellent ability to control disease recurrence. However, in some patients, disease
        response is suboptimal: understanding why this happens may open doors to more aggressive
        approaches, such as the combination with systemic therapies.
  
        Hence, the goal of this observational trial is to understand which clinical, imaging, and
        biological factors are associated with response to SBRT through the development of complex
        models. In other words, the main question it aims to answer is: "Will this patient respond to
        radiation treatment based on the characteristics of their disease?".
  
        Participants will be treated according to the best clinical practice standards, in agreement
        with international, national, and internal guidelines.
  
        Researchers will compare data collected from patients treated with SBRT with those collected
        from a similar group of patients, who will be treated with surgery, to see which factors are
        actual predictors of response to SBRT, or rather are indicators of more or less aggressive
        disease behavior.
  The overall planned duration of the study is 60 months.
  
        The project is structured into five main tasks, as following:
  
          -  Task 1_Clinical study: Routine clinical data will be collected from eligible patients,
             including demographics, disease and treatment characteristics, pulmonary function, and
             blood count parameters.
  
          -  Task 2_Radiomics study: Quantitative imaging analysis will be performed on both
             diagnostic computed tomographies (CTs) and positron emission tomographies (PETs). A
             software compliant with the Imaging Biomarker Standardization Initiative (IBSI) will be
             used to extract radiomic features at baseline and at the first clinical progression (or
             at the last available follow-up, whichever comes first). Clinically established
             qualitative and semiquantitative metrics (e.g. pleural effusion in CT images and
             standardized uptake value in PET images) will be retrieved, as well.
  
          -  Task 3_Gene expression study: Gene expression profiling will be performed at baseline in
             both cohorts to investigate the presence of a prognostic pretreatment signature. The
             analysis will be performed on formalin-fixed paraffin-embedded (FFPE) tissue samples
             (namely, resected tumor in the surgical cohort and bioptic sample- whenever available-
             in the SBRT group). A next-generation sequencing (NGS)-based assay which targets 395
             immune-related genes and named as Oncomine™ Immune Response Research Assay, will be
             employed.
  
          -  Task 4_Proteomics study: Proteomics will integrate the study of RNA expression performed
             in Task 3. As in Task 3, the analysis will be performed on FFPE samples, from both
             patients' cohorts.
  
          -  Task 5_Integrative model building: Integration of all previous features in a unique
             classification model able to determine a precise estimate of individuals with high vs
             low risk of disease progression and, at the same time, identify relevant predictive
             factors. The proposed classification model will integrate data from different sources
             using a multi-layer deep neural network. Federated learning techniques will also be used
             to reduce the bias due to the choice of a specific trial or data source.
  observational model: Cohort
  time perspective: Prospective
  measure: Progression-Free Survival (PFS)
  time frame: 24 months
  description: The time between the beginning of SBRT or date of surgery, and any disease progression (local, regional, distant), death from any cause, or last follow-up, whichever comes first.
  arm group label: SBRT Cohort
  description: Radiation: Stereotactic Body Radiotherapy (SBRT)
  arm group label: Surgery Cohort
  description: Procedure: Surgery
  intervention type: Radiation
  intervention name: SBRT
  description: State-of-art SBRT will be delivered in 3-5 fractions; prescription doses and fractionation schedules will be defined according to patient- and tumor-related characteristics (e.g. pulmonary comorbidities, tumor location: peripheral vs central vs ultra-central).
  arm group label: SBRT Cohort
  other name: Stereotactic body radiotherapy
  other name: Stereotactic Ablative Radiotherapy (SABR)
  intervention type: Procedure
  intervention name: Surgery
  description: State-of-art surgery will be consist in pulmonary anatomical resection (i.e. segmentectomy or lobectomy) and systematic lymph node dissection.
  arm group label: Surgery Cohort
  Formalin-fixed paraffin-embedded (FFPE) bioptic samples (SBRT cohort); formalin-fixed
        paraffin-embedded (FFPE) surgical specimens (surgical cohort)
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Stefania Volpe, MD
  role: Principal Investigator
  affiliation: Istituto Europeo di Oncologia IRCCS
  last name: Stefania Volpe, MD
  phone: +390257489037
  email: stefania.volpe@ieo.it
  last name: Cristiana Fodor, MSc
  phone: +390257489037
  email: cristiana.fodor@ieo.it
  facility: 
  country: Italy
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Neoplasms