<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/NCT03306680</url>
  </required_header>
  <id_info>
    <org_study_id>SUNSET</org_study_id>
    <nct_id>NCT03306680</nct_id>
  </id_info>
  <brief_title>SUNSET: SBRT for Ultra-central NSCLC- a Safety and Efficacy Trial</brief_title>
  <official_title>SUNSET: SBRT for Ultra-central NSCLC- a Safety and Efficacy Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawson Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lawson Health Research Institute</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multi-centre phase I dose-escalation study will use a time-to-event continual&#xD;
      reassessment method (TIT-CRM).&#xD;
&#xD;
      Accrual will start at level 1 (60 Gy in 8 fractions). Patients will be assigned to treatment&#xD;
      doses using the TITE-CRM model. The model will use all available information from previously&#xD;
      accrued patients to assign the highest dose with a predicted risk of grade 3 toxicity of 30%&#xD;
      or less.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will use a time-to-event continual reassessment method (TITE-CRM). The study&#xD;
      design is based on RTOG 0813 (described above), but with a more cautious approach, since the&#xD;
      patients herein may constitute a high-risk subset of the patients enrolled in RTOG 0813. The&#xD;
      modifications include a starting dose (60 Gy in 8 fractions) herein that is lower than the&#xD;
      safe dose for central tumors as determined by RTOG 0813 (60 Gy in 5 fractions), and longer&#xD;
      follow-up period during which patients are considered at-risk for toxicity, (i.e. two years&#xD;
      herein vs. one year in RTOG 0813).&#xD;
&#xD;
      The primary endpoint of this study is the maximally tolerated dose (MTD) of radiotherapy for&#xD;
      ultracentral tumors. The MTD is the dose of radiotherapy associated with a &lt;30% rate of grade&#xD;
      3-5 toxicity occurring within 2 years of treatment.&#xD;
&#xD;
      Local Progression, Regional nodal progression, Distant metastases, Progression-Free Survival,&#xD;
      Overall survival, patient reported outcomes and quality of life.&#xD;
&#xD;
      The correlative objectives of this study are to determine the prognostic value of ctDNA&#xD;
      levels measured pre-treatment, at the end of treatment and 3- and 12-months after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 19, 2018</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Actual">April 19, 2021</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>Maximally tolerated dose (MTD)</measure>
    <time_frame>Occurring within 2 years of treatment</time_frame>
    <description>MTD of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a &lt;30% rate of grade 3-5 toxicity occurring within 2 years of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Local Progression</measure>
    <time_frame>3-5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional nodal progression</measure>
    <time_frame>3-5 years</time_frame>
    <description>Defined as presence of enlarged lymph nodes &gt;1 cm [short axis] in the hilum or mediastinum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to distant metastases</measure>
    <time_frame>3-5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>3-5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3-5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcome</measure>
    <time_frame>Before treatment &amp; at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months</time_frame>
    <description>FACT-L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>Before treatment &amp; at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months</time_frame>
    <description>EQ-5D-5L</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Patients with ultra-central NSCLC T1-3 (&lt;6cm) N0 M0</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Level-1 Dose per fraction: 4Gy Number of fractions: 15 Total Dose: 60 Gy&#xD;
Level 0 Dose per fraction: 6Gy Number of fractions: 10 Total Dose: 60 Gy&#xD;
Level 1 Dose per fraction: 7.5 Gy Number of fractions: 8 Total Dose: 60 Gy</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>Patients will be assigned to treatment doses using the TITE-CRM model.</description>
    <arm_group_label>Patients with ultra-central NSCLC T1-3 (&lt;6cm) N0 M0</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically (histologically or cytologically) proven diagnosis of non-small cell&#xD;
             lung cancer (NSCLC); if the risk of biopsy is unacceptable, pathologic confirmation is&#xD;
             not required providing there is serial growth on serial (&gt;=2) CT imaging and/or FDG&#xD;
             avidity that is strongly suggestive of a primary NSCLC.&#xD;
&#xD;
          2. Stage T1-3, N0, M0 (UICC/AJCC Staging, 8th Ed.), tumor size &lt; 6 cm, prior to&#xD;
             registration, based upon the following minimum diagnostic workup:&#xD;
&#xD;
               1. History/physical examination within 4 weeks prior to registration&#xD;
&#xD;
               2. CT scan with contrast (unless medically contraindicated) within 12 weeks of&#xD;
                  registration. The CT scan will include the entirety of both lungs, the&#xD;
                  mediastinum, liver and adrenal glands; the primary tumor dimensions will be&#xD;
                  measured on CT. Note: Patients with lesions that cannot be visualized by CT scan&#xD;
                  are not eligible for the study.&#xD;
&#xD;
               3. Whole body positron emission tomography (PET) scan within 12 weeks of&#xD;
                  registration, using FDG with adequate visualization of the primary tumor and&#xD;
                  draining lymph node basins in the hilar and mediastinal regions.&#xD;
&#xD;
               4. Mediastinal lymph node sampling by any technique is encouraged but not required.&#xD;
                  Patients with hilar or mediastinal lymph nodes &lt;1 cm and no abnormal hilar or&#xD;
                  mediastinal uptake on PET will be considered N0. Patients with &gt; 1 cm hilar or&#xD;
                  mediastinal lymph nodes on CT or abnormal PET (including suspicious but&#xD;
                  nondiagnostic uptake) may still be eligible if directed tissue biopsies of all&#xD;
                  abnormally identified areas are negative for cancer.&#xD;
&#xD;
          3. ECOG performance status 0-2;&#xD;
&#xD;
          4. age &gt;18;&#xD;
&#xD;
          5. Ultra-central tumor location: tumours whose planning target volume (PTV) is expected&#xD;
             to touch or overlaps the central bronchial tree, esophagus, pulmonary vein, or&#xD;
             pulmonary artery as determined at the time of consultation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 2 years (e.g. carcinomas in situ of the breast, oral cavity, or&#xD;
             cervix are permissible); previous lung cancer, if the patient is disease-free for a&#xD;
             minimum of 2 years is permitted.&#xD;
&#xD;
          2. Any prior thoracic radiotherapy.&#xD;
&#xD;
          3. Any prior chemotherapy for the study cancer (cancer proposed to be treated on the&#xD;
             study).&#xD;
&#xD;
          4. Prior surgery for the study cancer.&#xD;
&#xD;
          5. Plans for the patient to receive other local therapy (including standard fractionated&#xD;
             radiotherapy and/or surgery) while on this study, except at disease progression;&#xD;
&#xD;
          6. Plans for the patient to receive systemic therapy (including standard chemotherapy or&#xD;
             biologic targeted agents), while on this study, except at disease progression.&#xD;
&#xD;
          7. Pregnancy.&#xD;
&#xD;
          8. The following autoimmune and connective tissue diseases will be excluded: Scleroderma&#xD;
             and Systemic lupus erythematosus&#xD;
&#xD;
          9. patients with interstitial lung disease (ILD).&#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>Meredith Giuliani, MBBS, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BC Cancer -Vancouver Island</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V8R 6V5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Odette Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Universite de Montreal (CHUM)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 0A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre-Cedars Cancer Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saskatoon Cancer Centre</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7S 0B1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2023</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>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/NCT03306680
org study id: SUNSET
nct id: NCT03306680
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This multi-centre phase I dose-escalation study will use a time-to-event continual
      reassessment method (TIT-CRM).

      Accrual will start at level 1 (60 Gy in 8 fractions). Patients will be assigned to treatment
      doses using the TITE-CRM model. The model will use all available information from previously
      accrued patients to assign the highest dose with a predicted risk of grade 3 toxicity of 30%
      or less.
This study will use a time-to-event continual reassessment method (TITE-CRM). The study
      design is based on RTOG 0813 (described above), but with a more cautious approach, since the
      patients herein may constitute a high-risk subset of the patients enrolled in RTOG 0813. The
      modifications include a starting dose (60 Gy in 8 fractions) herein that is lower than the
      safe dose for central tumors as determined by RTOG 0813 (60 Gy in 5 fractions), and longer
      follow-up period during which patients are considered at-risk for toxicity, (i.e. two years
      herein vs. one year in RTOG 0813).

      The primary endpoint of this study is the maximally tolerated dose (MTD) of radiotherapy for
      ultracentral tumors. The MTD is the dose of radiotherapy associated with a <30% rate of grade
      3-5 toxicity occurring within 2 years of treatment.

      Local Progression, Regional nodal progression, Distant metastases, Progression-Free Survival,
      Overall survival, patient reported outcomes and quality of life.

      The correlative objectives of this study are to determine the prognostic value of ctDNA
      levels measured pre-treatment, at the end of treatment and 3- and 12-months after treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximally tolerated dose (MTD)
time frame: Occurring within 2 years of treatment
description: MTD of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a <30% rate of grade 3-5 toxicity occurring within 2 years of treatment.
measure: Time to Local Progression
time frame: 3-5 years
measure: Regional nodal progression
time frame: 3-5 years
description: Defined as presence of enlarged lymph nodes >1 cm [short axis] in the hilum or mediastinum.
measure: Time to distant metastases
time frame: 3-5 years
measure: Progression-Free Survival
time frame: 3-5 years
measure: Overall survival
time frame: 3-5 years
measure: Patient reported outcome
time frame: Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
description: FACT-L
measure: Quality of Life
time frame: Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
description: EQ-5D-5L
arm group label: Patients with ultra-central NSCLC T1-3 (<6cm) N0 M0
arm group type: Experimental
description: Level-1 Dose per fraction: 4Gy Number of fractions: 15 Total Dose: 60 Gy
Level 0 Dose per fraction: 6Gy Number of fractions: 10 Total Dose: 60 Gy
Level 1 Dose per fraction: 7.5 Gy Number of fractions: 8 Total Dose: 60 Gy
intervention type: Radiation
intervention name: SBRT
description: Patients will be assigned to treatment doses using the TITE-CRM model.
arm group label: Patients with ultra-central NSCLC T1-3 (<6cm) N0 M0
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Meredith Giuliani, MBBS, FRCPC
role: Principal Investigator
affiliation: Princess Margaret Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No