<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/NCT03827577</url>
  </required_header>
  <id_info>
    <org_study_id>1533CESC</org_study_id>
    <nct_id>NCT03827577</nct_id>
  </id_info>
  <brief_title>OMEGA, Local Ablative Therapy in Oligometastatic NSCLC</brief_title>
  <acronym>OMEGA</acronym>
  <official_title>OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliera Universitaria Integrata Verona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>A.O.U. Città della Salute e della Scienza - Molinette Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>San Luigi Gonzaga Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regina Elena Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda Ospedaliera San Camillo Forlanini</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Humanitas Research Hospital Milan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Ospedaliera Universitaria Integrata Verona</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>
      Oligometastatic lung cancer (OM-NSCLC) seems to be associated with a better prognosis than&#xD;
      usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites&#xD;
      is administered but the impact of such an approach on overall survival and quality of life&#xD;
      remains to be defined by adequately powered phase III trials.&#xD;
&#xD;
      A consortium of tertiary referral centres involved in Lung Cancer management at the national&#xD;
      level was established to launch a randomized trial of local ablative therapy in OM-NSCLC&#xD;
      patients with potentially resectable or locally controlled primary tumors has been designed.&#xD;
&#xD;
      Inclusion criteria include adequate performance status, primary tumor controlled or&#xD;
      controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3&#xD;
      cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according&#xD;
      to molecular profile.&#xD;
&#xD;
      Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any&#xD;
      case), metastasis in sites where normal radiotherapy constraints cannot be met, multiple&#xD;
      subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some&#xD;
      exceptions, relevant co-morbidities that would significantly reduce life expectancy on their&#xD;
      own.&#xD;
&#xD;
      Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic&#xD;
      lesions) will be randomized to local ablative therapy + standard treatment Vs. standard&#xD;
      treatment. Balancing between study arms will be performed according to synchronous vs.&#xD;
      metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or&#xD;
      PDL-1 expression. Primary outcome will be Overall Survival (OS) from randomization. The&#xD;
      sample size is set to 195 patients.&#xD;
&#xD;
      Disease state and life status will be assessed on a 3-monthly basis by physical examination,&#xD;
      whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at&#xD;
      enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology&#xD;
      Criteria. And RTOG criteria. Quality of life will be assessed at randomization and after six&#xD;
      months by the SF36/LCSS&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung cancer is a systemic disease with local manifestations that are ultimately responsible&#xD;
      for a reduced life expectancy in a relatively large subgroup of metastatic lung cancer&#xD;
      patients.&#xD;
&#xD;
      In such a subgroup, local ablative therapy of the primary tumor and of all metastatic lesions&#xD;
      with a combination of surgery and/or radiotherapy should lead to a clinically significant&#xD;
      improvement of their overall survival with acceptable morbidity and preserved Quality of Life&#xD;
      compared with medical treatment alone&#xD;
&#xD;
      OMEGA is a randomized trial of local ablative therapy in NSCLC patients with potentially&#xD;
      resectable or locally controlled primary tumors and oligometastatic disease&#xD;
&#xD;
      The decision to randomise OM-NSCLC patients either before any systemic therapy or after 3&#xD;
      months of treatment without progression is left to the recruiting centre(s).&#xD;
&#xD;
      Local ablative therapy will be administered in any case to patients harboring cerebral&#xD;
      oligometastasis&#xD;
&#xD;
      Statistical methods&#xD;
&#xD;
      Dynamic balancing as per the method of Pocock and Simon [16] according to:&#xD;
&#xD;
        -  Synchronous vs. metachronous presentation&#xD;
&#xD;
        -  Number of oligometastases (1 vs. 2-3) including extrathoracic N3 disease&#xD;
&#xD;
        -  Nodal status (N0 vs. N+)&#xD;
&#xD;
        -  Oncogene-addiction (EGFR/ALK/ROS-1 driven or PDL1 &gt;50% vs &lt;50% vs. wild type)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>from date of randomization until date of death from any cause up to 60 months</time_frame>
    <description>time interval from randomization until death from any cause</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">195</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>LAT arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lung resection (if primary in place) + local ablative therapy of all metastatic sites + standard medical treatment.&#xD;
patients may be enrolled either before any systemic therapy or after 3 months of treatment without progression according to local coordinator decision</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard medical treatment&#xD;
Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical removal of primary and/or of all oligometastases</intervention_name>
    <description>Standard lobectomy or segmentectomy if tumor resectable without pneumonectomy (prefer lobectomy if cardiorespiratory function is not or only moderately compromised, prefer segmentectomy if primary tumor less than 2 cm or cardiorespiratory function is more than moderately compromised but still permissive) Mediastinal lymph node dissection (at least 8 lymphnodes from at least 3 stations including station 7).</description>
    <arm_group_label>LAT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Non-surgical LAT</intervention_name>
    <description>Non-surgical LAT may be carried out either by SABR or SBRT or RFA according to site of metastasis, local expertise and availability of resources.</description>
    <arm_group_label>LAT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard medical therapy</intervention_name>
    <description>platinum-based doublet according to local protocols or targeted agents according to EGFR/ALK/ROS-1 mutational status or immunotherapy agents according to PDL1 expression.</description>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_label>LAT arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  ECOG performance status 0-1 at the time of randomization&#xD;
&#xD;
          -  Pathologically confirmed NSCLC.&#xD;
&#xD;
          -  Staging with whole-body FDG PET scan and brain MRI or CT with IV contrast.&#xD;
&#xD;
          -  Between 1 and 3 metastatic lesions, assessable according to RECIST v1.1 and suitable&#xD;
             for LAT prior to trial registration.&#xD;
&#xD;
          -  Primary tumor controlled (metachronous oligometastasis) or resectable/suitable for&#xD;
             ablative radiotherapy.&#xD;
&#xD;
          -  Patient is deemed fit to receive at least 3 cycles of platinum-based doublet&#xD;
             chemotherapy, cisplatin or carboplatin, according to local guidelines.&#xD;
&#xD;
          -  If pulmonary involvement, it must be bilateral with at least 3 lung lesions, or&#xD;
             extrapulmonary metastasis must be present&#xD;
&#xD;
          -  If brain involvement, up to 2 brain metastases, the largest brain lesion &lt; 3cm in&#xD;
             maximum diameter at the time of randomization.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Any tumor site besides brain metastasis requiring immediate LAT for palliation.&#xD;
&#xD;
          -  Patient has received previous LAT for extra-cerebral metastasis&#xD;
&#xD;
          -  Patient has received previous systemic treatment for his/her NSCLC malignancy and is&#xD;
             experiencing disease progression at the time of randomization (except adjuvant&#xD;
             chemotherapy and/or radiotherapy more than 6 months earlier)&#xD;
&#xD;
          -  Patient has had palliative radiotherapy to any tumor site prior to registration and/or&#xD;
             requires palliative radiotherapy prior to randomization.&#xD;
&#xD;
          -  High clinical suspicion of direct invasion of the wall of any major blood vessel or&#xD;
             medulla by the primary tumor or metastasis&#xD;
&#xD;
          -  Brain metastasis within the brainstem, or leptomeningeal disease.&#xD;
&#xD;
          -  Metastasis in sites where normal radiotherapy constraints cannot be met or in a&#xD;
             previously irradiated area&#xD;
&#xD;
          -  Malignant pleural or pericardial effusion.&#xD;
&#xD;
          -  Lung tumors with a single additional nodule in the same lobe, same lung or in the&#xD;
             contralateral lung, i.e. T3, T4 or M1a lung cancer, in the absence of extrapulmonary&#xD;
             involvement.&#xD;
&#xD;
          -  Lung involvement in the form of multiple nonsolid or subsolid nodules, in the absence&#xD;
             of extrapulmonary metastasis [18]&#xD;
&#xD;
          -  History of prior malignant tumour likely to interfere with the protocol treatment or&#xD;
             comparisons (excluding H&amp;N primary, radically treated, no recurrence over the last 5&#xD;
             years, non-melanoma skin cancer, in situ cervical cancer, DCIS or LCIS of the breast&#xD;
&#xD;
          -  Any relevant co-morbidities that would significantly reduce life expectancy on their&#xD;
             own, such as heart failure, advanced COPD, uncontrolled diabetes, end-stage renal&#xD;
             disease etc.&#xD;
&#xD;
          -  Women who are pregnant or breast feeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maurizio V Infante</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera Universitaria Integrata Verona</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michele Milella, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera Universitaria Integrata Verona</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emilio Bria, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maurizio V Infante, MD</last_name>
    <phone>+390458123335</phone>
    <email>maurizio.infante@aovr.veneto.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sara Pilotto, MD</last_name>
    <email>sara.pilotto@univr.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Integrata</name>
      <address>
        <city>Verona</city>
        <zip>37126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maurizio V Infante, MD</last_name>
      <email>maurizio.infante@aovr.veneto.it</email>
    </contact>
    <investigator>
      <last_name>Sara Pilotto, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maurizio V Infante, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Antonio Santo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Torok JA, Gu L, Tandberg DJ, Wang X, Harpole DH Jr, Kelsey CR, Salama JK. Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer. Clin Lung Cancer. 2017 Jan;18(1):e57-e70. doi: 10.1016/j.cllc.2016.06.011. Epub 2016 Jul 5.</citation>
    <PMID>27477488</PMID>
  </reference>
  <reference>
    <citation>Johnson KK, Rosen JE, Salazar MC, Boffa DJ. Outcomes of a Highly Selective Surgical Approach to Oligometastatic Lung Cancer. Ann Thorac Surg. 2016 Oct;102(4):1166-71. doi: 10.1016/j.athoracsur.2016.04.086. Epub 2016 Jun 23.</citation>
    <PMID>27344278</PMID>
  </reference>
  <reference>
    <citation>Ashworth AB, Senan S, Palma DA, Riquet M, Ahn YC, Ricardi U, Congedo MT, Gomez DR, Wright GM, Melloni G, Milano MT, Sole CV, De Pas TM, Carter DL, Warner AJ, Rodrigues GB. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer. 2014 Sep;15(5):346-55. doi: 10.1016/j.cllc.2014.04.003. Epub 2014 May 15.</citation>
    <PMID>24894943</PMID>
  </reference>
  <reference>
    <citation>Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.</citation>
    <PMID>27789196</PMID>
  </reference>
  <reference>
    <citation>Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018 Jan 11;4(1):e173501. doi: 10.1001/jamaoncol.2017.3501. Epub 2018 Jan 11.</citation>
    <PMID>28973074</PMID>
  </reference>
  <reference>
    <citation>Yamaguchi M, Edagawa M, Suzuki Y, Toyozawa R, Hirai F, Nosaki K, Seto T, Takenoyama M, Ichinose Y. Pulmonary Resection for Synchronous M1b-cStage IV Non-Small Cell Lung Cancer Patients. Ann Thorac Surg. 2017 May;103(5):1594-1599. doi: 10.1016/j.athoracsur.2016.08.098. Epub 2016 Nov 15.</citation>
    <PMID>27863731</PMID>
  </reference>
  <reference>
    <citation>Detterbeck FC, Franklin WA, Nicholson AG, Girard N, Arenberg DA, Travis WD, Mazzone PJ, Marom EM, Donington JS, Tanoue LT, Rusch VW, Asamura H, Rami-Porta R; IASLC Staging and Prognostic Factors Committee; Advisory Boards; Multiple Pulmonary Sites Workgroup. The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016 May;11(5):651-665. doi: 10.1016/j.jtho.2016.01.025. Epub 2016 Mar 2.</citation>
    <PMID>26944304</PMID>
  </reference>
  <reference>
    <citation>Conibear J, Chia B, Ngai Y, Bates AT, Counsell N, Patel R, Eaton D, Faivre-Finn C, Fenwick J, Forster M, Hanna GG, Harden S, Mayles P, Moinuddin S, Landau D. Study protocol for the SARON trial: a multicentre, randomised controlled phase III trial comparing the addition of stereotactic ablative radiotherapy and radical radiotherapy with standard chemotherapy alone for oligometastatic non-small cell lung cancer. BMJ Open. 2018 Apr 17;8(4):e020690. doi: 10.1136/bmjopen-2017-020690. Erratum In: BMJ Open. 2019 May 9;9(5):e020690corr1.</citation>
    <PMID>29666135</PMID>
  </reference>
  <reference>
    <citation>Detterbeck FC, Marom EM, Arenberg DA, Franklin WA, Nicholson AG, Travis WD, Girard N, Mazzone PJ, Donington JS, Tanoue LT, Rusch VW, Asamura H, Rami-Porta R; IASLC Staging and Prognostic Factors Committee; Advisory Boards; Multiple Pulmonary Sites Workgroup. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification. J Thorac Oncol. 2016 May;11(5):666-680. doi: 10.1016/j.jtho.2015.12.113. Epub 2016 Mar 3.</citation>
    <PMID>26940527</PMID>
  </reference>
  <reference>
    <citation>Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.</citation>
    <PMID>1100130</PMID>
  </reference>
  <reference>
    <citation>https://evs.nci.nih.gov/ftp1/CTCAE/About.html</citation>
  </reference>
  <reference>
    <citation>Seely AJ, Ivanovic J, Threader J, Al-Hussaini A, Al-Shehab D, Ramsay T, Gilbert S, Maziak DE, Shamji FM, Sundaresan RS. Systematic classification of morbidity and mortality after thoracic surgery. Ann Thorac Surg. 2010 Sep;90(3):936-42; discussion 942. doi: 10.1016/j.athoracsur.2010.05.014.</citation>
    <PMID>20732521</PMID>
  </reference>
  <reference>
    <citation>Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. doi: 10.1016/0360-3016(95)00060-C. No abstract available.</citation>
    <PMID>7713792</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03827577
org study id: 1533CESC
nct id: NCT03827577
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Oligometastatic lung cancer (OM-NSCLC) seems to be associated with a better prognosis than
      usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites
      is administered but the impact of such an approach on overall survival and quality of life
      remains to be defined by adequately powered phase III trials.

      A consortium of tertiary referral centres involved in Lung Cancer management at the national
      level was established to launch a randomized trial of local ablative therapy in OM-NSCLC
      patients with potentially resectable or locally controlled primary tumors has been designed.

      Inclusion criteria include adequate performance status, primary tumor controlled or
      controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3
      cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according
      to molecular profile.

      Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any
      case), metastasis in sites where normal radiotherapy constraints cannot be met, multiple
      subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some
      exceptions, relevant co-morbidities that would significantly reduce life expectancy on their
      own.

      Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic
      lesions) will be randomized to local ablative therapy + standard treatment Vs. standard
      treatment. Balancing between study arms will be performed according to synchronous vs.
      metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or
      PDL-1 expression. Primary outcome will be Overall Survival (OS) from randomization. The
      sample size is set to 195 patients.

      Disease state and life status will be assessed on a 3-monthly basis by physical examination,
      whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at
      enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology
      Criteria. And RTOG criteria. Quality of life will be assessed at randomization and after six
      months by the SF36/LCSS
Lung cancer is a systemic disease with local manifestations that are ultimately responsible
      for a reduced life expectancy in a relatively large subgroup of metastatic lung cancer
      patients.

      In such a subgroup, local ablative therapy of the primary tumor and of all metastatic lesions
      with a combination of surgery and/or radiotherapy should lead to a clinically significant
      improvement of their overall survival with acceptable morbidity and preserved Quality of Life
      compared with medical treatment alone

      OMEGA is a randomized trial of local ablative therapy in NSCLC patients with potentially
      resectable or locally controlled primary tumors and oligometastatic disease

      The decision to randomise OM-NSCLC patients either before any systemic therapy or after 3
      months of treatment without progression is left to the recruiting centre(s).

      Local ablative therapy will be administered in any case to patients harboring cerebral
      oligometastasis

      Statistical methods

      Dynamic balancing as per the method of Pocock and Simon [16] according to:

        -  Synchronous vs. metachronous presentation

        -  Number of oligometastases (1 vs. 2-3) including extrathoracic N3 disease

        -  Nodal status (N0 vs. N+)

        -  Oncogene-addiction (EGFR/ALK/ROS-1 driven or PDL1 >50% vs <50% vs. wild type)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: from date of randomization until date of death from any cause up to 60 months
description: time interval from randomization until death from any cause
arm group label: LAT arm
arm group type: Experimental
description: Lung resection (if primary in place) + local ablative therapy of all metastatic sites + standard medical treatment.
patients may be enrolled either before any systemic therapy or after 3 months of treatment without progression according to local coordinator decision
arm group label: Control Arm
arm group type: Active Comparator
description: Standard medical treatment
Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases
intervention type: Procedure
intervention name: Surgical removal of primary and/or of all oligometastases
description: Standard lobectomy or segmentectomy if tumor resectable without pneumonectomy (prefer lobectomy if cardiorespiratory function is not or only moderately compromised, prefer segmentectomy if primary tumor less than 2 cm or cardiorespiratory function is more than moderately compromised but still permissive) Mediastinal lymph node dissection (at least 8 lymphnodes from at least 3 stations including station 7).
arm group label: LAT arm
intervention type: Radiation
intervention name: Non-surgical LAT
description: Non-surgical LAT may be carried out either by SABR or SBRT or RFA according to site of metastasis, local expertise and availability of resources.
arm group label: LAT arm
intervention type: Drug
intervention name: Standard medical therapy
description: platinum-based doublet according to local protocols or targeted agents according to EGFR/ALK/ROS-1 mutational status or immunotherapy agents according to PDL1 expression.
arm group label: Control Arm
arm group label: LAT arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Maurizio V Infante
role: Principal Investigator
affiliation: Azienda Ospedaliera Universitaria Integrata Verona
last name: Michele Milella, PhD
role: Principal Investigator
affiliation: Azienda Ospedaliera Universitaria Integrata Verona
last name: Emilio Bria, PhD
role: Principal Investigator
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
last name: Maurizio V Infante, MD
phone: +390458123335
email: maurizio.infante@aovr.veneto.it
last name: Sara Pilotto, MD
email: sara.pilotto@univr.it
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: Italy
citation: Torok JA, Gu L, Tandberg DJ, Wang X, Harpole DH Jr, Kelsey CR, Salama JK. Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer. Clin Lung Cancer. 2017 Jan;18(1):e57-e70. doi: 10.1016/j.cllc.2016.06.011. Epub 2016 Jul 5.
PMID: 27477488
citation: Johnson KK, Rosen JE, Salazar MC, Boffa DJ. Outcomes of a Highly Selective Surgical Approach to Oligometastatic Lung Cancer. Ann Thorac Surg. 2016 Oct;102(4):1166-71. doi: 10.1016/j.athoracsur.2016.04.086. Epub 2016 Jun 23.
PMID: 27344278
citation: Ashworth AB, Senan S, Palma DA, Riquet M, Ahn YC, Ricardi U, Congedo MT, Gomez DR, Wright GM, Melloni G, Milano MT, Sole CV, De Pas TM, Carter DL, Warner AJ, Rodrigues GB. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer. 2014 Sep;15(5):346-55. doi: 10.1016/j.cllc.2014.04.003. Epub 2014 May 15.
PMID: 24894943
citation: Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.
PMID: 27789196
citation: Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018 Jan 11;4(1):e173501. doi: 10.1001/jamaoncol.2017.3501. Epub 2018 Jan 11.
PMID: 28973074
citation: Yamaguchi M, Edagawa M, Suzuki Y, Toyozawa R, Hirai F, Nosaki K, Seto T, Takenoyama M, Ichinose Y. Pulmonary Resection for Synchronous M1b-cStage IV Non-Small Cell Lung Cancer Patients. Ann Thorac Surg. 2017 May;103(5):1594-1599. doi: 10.1016/j.athoracsur.2016.08.098. Epub 2016 Nov 15.
PMID: 27863731
citation: Detterbeck FC, Franklin WA, Nicholson AG, Girard N, Arenberg DA, Travis WD, Mazzone PJ, Marom EM, Donington JS, Tanoue LT, Rusch VW, Asamura H, Rami-Porta R; IASLC Staging and Prognostic Factors Committee; Advisory Boards; Multiple Pulmonary Sites Workgroup. The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016 May;11(5):651-665. doi: 10.1016/j.jtho.2016.01.025. Epub 2016 Mar 2.
PMID: 26944304
citation: Conibear J, Chia B, Ngai Y, Bates AT, Counsell N, Patel R, Eaton D, Faivre-Finn C, Fenwick J, Forster M, Hanna GG, Harden S, Mayles P, Moinuddin S, Landau D. Study protocol for the SARON trial: a multicentre, randomised controlled phase III trial comparing the addition of stereotactic ablative radiotherapy and radical radiotherapy with standard chemotherapy alone for oligometastatic non-small cell lung cancer. BMJ Open. 2018 Apr 17;8(4):e020690. doi: 10.1136/bmjopen-2017-020690. Erratum In: BMJ Open. 2019 May 9;9(5):e020690corr1.
PMID: 29666135
citation: Detterbeck FC, Marom EM, Arenberg DA, Franklin WA, Nicholson AG, Travis WD, Girard N, Mazzone PJ, Donington JS, Tanoue LT, Rusch VW, Asamura H, Rami-Porta R; IASLC Staging and Prognostic Factors Committee; Advisory Boards; Multiple Pulmonary Sites Workgroup. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification. J Thorac Oncol. 2016 May;11(5):666-680. doi: 10.1016/j.jtho.2015.12.113. Epub 2016 Mar 3.
PMID: 26940527
citation: Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.
PMID: 1100130
citation: https://evs.nci.nih.gov/ftp1/CTCAE/About.html
citation: Seely AJ, Ivanovic J, Threader J, Al-Hussaini A, Al-Shehab D, Ramsay T, Gilbert S, Maziak DE, Shamji FM, Sundaresan RS. Systematic classification of morbidity and mortality after thoracic surgery. Ann Thorac Surg. 2010 Sep;90(3):936-42; discussion 942. doi: 10.1016/j.athoracsur.2010.05.014.
PMID: 20732521
citation: Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. doi: 10.1016/0360-3016(95)00060-C. No abstract available.
PMID: 7713792
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: Undecided