<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/NCT04455438</url>
  </required_header>
  <id_info>
    <org_study_id>2525</org_study_id>
    <nct_id>NCT04455438</nct_id>
  </id_info>
  <brief_title>SBRT Dose Escalation for Reirradiation of Inoperable Lung Lesions</brief_title>
  <acronym>STRILL</acronym>
  <official_title>Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Reirradiation of Inoperable Lung Lesions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Clinico Humanitas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Clinico Humanitas</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>
      Prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic&#xD;
      re-irradiation. Dose limiting toxicity will be pneumonitis ≥ G3. The potential advantage of&#xD;
      the dose escalation planned in this study is the delivery of an ablative dose to radically&#xD;
      treat patients with inoperable local relapse, without unacceptable toxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Radical dose radiotherapy (RT) is frequently used in thoracic malignancies, both for early&#xD;
      stage primary non-small cell lung cancer (NSCLC) and for secondary lesions from other primary&#xD;
      tumors, particularly in the setting of oligometastatic patients. Although development of&#xD;
      distant metastases is the predominant pattern of failure after treatment with radical RT,&#xD;
      isolated local recurrences, defined as a tumor recurrence overlapping the 50% isodose field,&#xD;
      are still observed and are becoming more and more frequent along with the prolongation of&#xD;
      life expectancy in cancer patients. Salvage options for isolated post-radiation local&#xD;
      failures are limited, with surgery or retreatment with radiotherapy as potential modalities.&#xD;
&#xD;
      While salvage surgical resection after previous thoracic irradiation has shown encouraging&#xD;
      results, most patients experiencing post-radiation local relapse are not surgical candidates.&#xD;
      Therefore, reirradiation may be the only viable salvage option for many patients. Retreatment&#xD;
      with CFRT has been reported for locoregional failures, with generally-poor outcomes.&#xD;
      Although, salvage SBRT after initial CFRT has been described in select small series of&#xD;
      heterogeneous patient groups ranging from early stage to locally-advanced and metastatic, few&#xD;
      data exist to guide us on the role of reirradiation with SBRT for isolated recurrences after&#xD;
      initial SBRT for early-stage NSCLC. Due to the heterogeneity and the low numerosity of these&#xD;
      experiences, important questions regarding the safety and efficacy in this setting are still&#xD;
      largely unanswered. Particularly, the possibility of delivering a second course of ablative&#xD;
      dose RT (BED ≥ 100 Gy) is almost unexplored.&#xD;
&#xD;
      Based on this background, we designed a prospective phase I study to evaluate the maximum&#xD;
      tolerated dose (MTD) of SBRT for thoracic re-irradiation. Dose limiting toxicity will be&#xD;
      pneumonitis ≥ G3. The potential advantage of the dose escalation planned in this study is the&#xD;
      delivery of an ablative dose to radically treat patients with inoperable local relapse,&#xD;
      without unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>The study is designed to determine the Maximum Tolerated Dose (MTD) that could be safely delivered in the lung reirradiation setting. The MTD was defined as the highest dose level in which a proportion of 1 out of 5 or fewer patients experienced DLT. Due to the late onset nature of DLT, in order to allow for continuous accrual without sacrificing patient safety or the accuracy of identifying the MTD, the Time-To-Event Bayesian Optimal Interval (TITE-BOIN) design will be used.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MTD</measure>
    <time_frame>5 years</time_frame>
    <description>maximal tolerated dose (MTD) of SBRT for thoracic re-irradiation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Other toxicities</measure>
    <time_frame>5 years</time_frame>
    <description>To evaluate acute and late toxicities other than dose limiting toxicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>To evaluate overall survival of patients undergoing thoracic re-irradiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local control</measure>
    <time_frame>5 years</time_frame>
    <description>To evaluate local control of patients undergoing thoracic re-irradiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>5 years</time_frame>
    <description>To evaluate progression free survival of patients undergoing thoracic re-irradiation.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Lung Metastases</condition>
  <arm_group>
    <arm_group_label>SBRT Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The starting dose level will be SBRT 30 Gy in 5 fractions (level 1 or L1).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SBRT Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>If the starting dose is tolerated in the first 5 patients, the next dose will be SBRT 40 Gy in 5 fractions (level 2 or L2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SBRT Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>If the second dose is tolerated in the next 5 patients, the next dose will be SBRT 50 Gy in 5 fractions (level 3 or L3)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT dose escalation</intervention_name>
    <description>Re-Stereotactic Body Radiation Therapy (SBRT) with increasing dose levels, from 30 Gy in 5 fractions to 50 Gy in 5 fractions.</description>
    <arm_group_label>SBRT Level 1</arm_group_label>
    <arm_group_label>SBRT Level 2</arm_group_label>
    <arm_group_label>SBRT Level 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inoperable primary non-small cell lung cancer or other metastatic primaries with lung&#xD;
             metastases, already treated with radical dose RT;&#xD;
&#xD;
          -  Peripheral lesion (&gt; 2 cm from trachea-bronchial tree);&#xD;
&#xD;
          -  Inoperable local recurrence (defined as a tumor recurrence overlapping the 50% isodose&#xD;
             field) confirmed by documented radiographic findings and/or pathological biopsies&#xD;
             within the thoracic area;&#xD;
&#xD;
          -  Patients had previously received curative intent RT of more than 50 Gy for&#xD;
             conventionally fractionated RT or a biologically equivalent dose of more than 75 Gy&#xD;
             for SBRT;&#xD;
&#xD;
          -  No active distant metastasis or controlled distant metastasis at the time of&#xD;
             re-irradiation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Central or ultra-central lesion(s);&#xD;
&#xD;
          -  Incapability of understanding and signing 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_contact>
    <last_name>Davide Franceschini, MD</last_name>
    <phone>0039 028224 7428</phone>
    <email>davide.franceschini@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Federico Fornasier, M.Sc</last_name>
    <phone>0039 028224 7026</phone>
    <email>federico.fornasier@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Humanitas Research Hospital</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Davide Franceschini, MD</last_name>
      <phone>+39 0282247428</phone>
      <email>davide.franceschini@humanitas.it</email>
    </contact>
    <contact_backup>
      <last_name>Mauro Loi, MD</last_name>
      <phone>+39 0282247461</phone>
      <email>mauro.loi@humanitas.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>September 14, 2022</last_update_submitted>
  <last_update_submitted_qc>September 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</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/NCT04455438
org study id: 2525
nct id: NCT04455438
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic
      re-irradiation. Dose limiting toxicity will be pneumonitis ≥ G3. The potential advantage of
      the dose escalation planned in this study is the delivery of an ablative dose to radically
      treat patients with inoperable local relapse, without unacceptable toxicity.
Radical dose radiotherapy (RT) is frequently used in thoracic malignancies, both for early
      stage primary non-small cell lung cancer (NSCLC) and for secondary lesions from other primary
      tumors, particularly in the setting of oligometastatic patients. Although development of
      distant metastases is the predominant pattern of failure after treatment with radical RT,
      isolated local recurrences, defined as a tumor recurrence overlapping the 50% isodose field,
      are still observed and are becoming more and more frequent along with the prolongation of
      life expectancy in cancer patients. Salvage options for isolated post-radiation local
      failures are limited, with surgery or retreatment with radiotherapy as potential modalities.

      While salvage surgical resection after previous thoracic irradiation has shown encouraging
      results, most patients experiencing post-radiation local relapse are not surgical candidates.
      Therefore, reirradiation may be the only viable salvage option for many patients. Retreatment
      with CFRT has been reported for locoregional failures, with generally-poor outcomes.
      Although, salvage SBRT after initial CFRT has been described in select small series of
      heterogeneous patient groups ranging from early stage to locally-advanced and metastatic, few
      data exist to guide us on the role of reirradiation with SBRT for isolated recurrences after
      initial SBRT for early-stage NSCLC. Due to the heterogeneity and the low numerosity of these
      experiences, important questions regarding the safety and efficacy in this setting are still
      largely unanswered. Particularly, the possibility of delivering a second course of ablative
      dose RT (BED ≥ 100 Gy) is almost unexplored.

      Based on this background, we designed a prospective phase I study to evaluate the maximum
      tolerated dose (MTD) of SBRT for thoracic re-irradiation. Dose limiting toxicity will be
      pneumonitis ≥ G3. The potential advantage of the dose escalation planned in this study is the
      delivery of an ablative dose to radically treat patients with inoperable local relapse,
      without unacceptable toxicity.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: The study is designed to determine the Maximum Tolerated Dose (MTD) that could be safely delivered in the lung reirradiation setting. The MTD was defined as the highest dose level in which a proportion of 1 out of 5 or fewer patients experienced DLT. Due to the late onset nature of DLT, in order to allow for continuous accrual without sacrificing patient safety or the accuracy of identifying the MTD, the Time-To-Event Bayesian Optimal Interval (TITE-BOIN) design will be used.
primary purpose: Treatment
masking: None (Open Label)
measure: MTD
time frame: 5 years
description: maximal tolerated dose (MTD) of SBRT for thoracic re-irradiation
measure: Other toxicities
time frame: 5 years
description: To evaluate acute and late toxicities other than dose limiting toxicity
measure: Overall survival
time frame: 5 years
description: To evaluate overall survival of patients undergoing thoracic re-irradiation.
measure: Local control
time frame: 5 years
description: To evaluate local control of patients undergoing thoracic re-irradiation.
measure: PFS
time frame: 5 years
description: To evaluate progression free survival of patients undergoing thoracic re-irradiation.
arm group label: SBRT Level 1
arm group type: Experimental
description: The starting dose level will be SBRT 30 Gy in 5 fractions (level 1 or L1).
arm group label: SBRT Level 2
arm group type: Experimental
description: If the starting dose is tolerated in the first 5 patients, the next dose will be SBRT 40 Gy in 5 fractions (level 2 or L2)
arm group label: SBRT Level 3
arm group type: Experimental
description: If the second dose is tolerated in the next 5 patients, the next dose will be SBRT 50 Gy in 5 fractions (level 3 or L3)
intervention type: Radiation
intervention name: SBRT dose escalation
description: Re-Stereotactic Body Radiation Therapy (SBRT) with increasing dose levels, from 30 Gy in 5 fractions to 50 Gy in 5 fractions.
arm group label: SBRT Level 1
arm group label: SBRT Level 2
arm group label: SBRT Level 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Davide Franceschini, MD
phone: 0039 028224 7428
email: davide.franceschini@gmail.com
last name: Federico Fornasier, M.Sc
phone: 0039 028224 7026
email: federico.fornasier@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Italy
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No