<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/NCT04476797</url>
  </required_header>
  <id_info>
    <org_study_id>GTI-4711-101</org_study_id>
    <nct_id>NCT04476797</nct_id>
  </id_info>
  <brief_title>Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC</brief_title>
  <acronym>GRECO-1</acronym>
  <official_title>GRECO-1: Phase I/II, Randomized, Placebo-Controlled Study of Stereotactic Body Radiation Therapy (SBRT) and GC4711 for Centrally Located or Large, Node-Negative Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Galera Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Galera Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      GTI-4711-101 is a Phase I/II study of the safety of GC4711, its effect on in-field tumor&#xD;
      response and its potential to reduce radiation-related pulmonary injury due to SBRT for lymph&#xD;
      node negative (T1 to T3N0M0) peripheral or central localized (within 2cm of the proximal&#xD;
      bronchial tree) NSCLC.&#xD;
&#xD;
      After an open-label, Phase 1, safety cohort of 5 subjects has been completed, a randomized,&#xD;
      placebo-controlled Phase 2 portion of 66 subjects will be conducted.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects must be referred for SBRT with large peripheral lesions (&gt;1cm-7cm) and/or central&#xD;
      localized, node negative, non-metastatic NSCLC, and have an ECOG PS score of 0-3. Feasibility&#xD;
      of SBRT is judged by the treating physician.&#xD;
&#xD;
      SBRT is planned for the tumor location as a dose of or 3 fractions of 18-20 Gy (Phase 2 only)&#xD;
      or 5 fractions of 10-12 Gy. SBRT fractions will be given within 180 minutes from the end of&#xD;
      the GC4711 or placebo infusion.&#xD;
&#xD;
      After completion of Phase I, a Phase II, randomized, placebo-controlled study will be&#xD;
      initiated, wherein approximately 66 subjects referred for SBRT with early stage large and/or&#xD;
      central localized NSCLC will be randomized in a 1:1 ratio to receive either GC4711 or placebo&#xD;
      given intravenously (IV) over 15 minutes before each fraction of SBRT, beginning the day of&#xD;
      the first fraction of SBRT and ending the last day of SBRT.&#xD;
&#xD;
      Subjects will be monitored for treatment emergent adverse events for 30 days post SBRT&#xD;
      completion. Additionally, subjects will be monitored 90 days post-SBRT for all adverse events&#xD;
      to evaluate acute toxicities, and monitored for 1-year post-SBRT completion for specific late&#xD;
      toxicities.&#xD;
&#xD;
      In-field tumor response and overall survival will be evaluated through 24 months post SBRT&#xD;
      completion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 18, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
    <intervention_model_description>After the open label Phase 1 portion, subjects in the Phase2 portion will be randomized in a 1:1 ratio to receive GC4711 or placebo before each fraction of SBRT</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Phase 2 is a randomized, placebo-controlled study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of dose-limiting toxicities during treatment and within 30 days post SBRT</measure>
    <time_frame>DLT 30 days post SBRT</time_frame>
    <description>Phase 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of patients with a best RECIST response of CR or PR amongst all responses through Month 6</measure>
    <time_frame>6 months post SBRT</time_frame>
    <description>Phase 2</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">71</enrollment>
  <condition>SBRT</condition>
  <condition>NSCLC</condition>
  <condition>Non-metastatic</condition>
  <arm_group>
    <arm_group_label>GC4711 + SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + SBRT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GC4711</intervention_name>
    <description>15 minute IV Infusion prior to SBRT</description>
    <arm_group_label>GC4711 + SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>15 minute IV infusion prior to SBRT</description>
    <arm_group_label>Placebo + SBRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects at least 18 years of age.&#xD;
&#xD;
          2. Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
          3. Histological or biopsy proven NSCLC.&#xD;
&#xD;
          4. ECOG performance status of 0-3.&#xD;
&#xD;
          5. Node negative (T1 to T3N0M0), centrally located (within 2cm in all directions around&#xD;
             the proximal bronchial tree, including ultra-central tumors, abutting the bronchial&#xD;
             tree or trachea) or large (&gt;1-7cm) Non-Small Cell Lung Cancer (NSCLC), judged&#xD;
             acceptable for SBRT by the treating Investigator&#xD;
&#xD;
          6. Adequate end-organ function, based on routine clinical and laboratory workup:&#xD;
&#xD;
               1. ANC &gt;1,000 cells/µl, Platelets ≥ 75,000 cells/µl, Hemoglobin ≥ 7.0 g/dl&#xD;
&#xD;
               2. Serum creatinine ≤ 2 x ULN or calculated creatinine clearance ≥ 30 ml/min&#xD;
&#xD;
               3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤&#xD;
                  2.5 x ULN&#xD;
&#xD;
          7. Males and females of must agree to use effective contraception starting prior to the&#xD;
             first day of treatment and continuing after the last dose of GC4711/Placebo for 30&#xD;
             days (females) and 90 days (males).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with confirmed nodal and/or distant disease(including brain), according&#xD;
             standard workup by local investigator&#xD;
&#xD;
          2. Subjects with peripheral lesions 1cm or smaller&#xD;
&#xD;
          3. Prior treatment with immunotherapy within 3 months prior to Day 1 dosing.&#xD;
&#xD;
          4. Prior intra-thoracic radiotherapy or surgery with substantial overlap to planned&#xD;
             radiation fields as determined by the treating radiation oncologist.&#xD;
&#xD;
          5. Subjects not recovered/controlled from prior treatment-related (chemotherapy or&#xD;
             targeted therapy) toxicities judged by treating physician.&#xD;
&#xD;
          6. Uncontrolled malignancy other than lung cancer that requires active treatment or is&#xD;
             deemed by the treating physicians to be likely to affect the subject's survival&#xD;
             duration.&#xD;
&#xD;
          7. History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to GC4711.&#xD;
&#xD;
          8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that, in the opinion of the&#xD;
             investigator, would limit compliance with study requirements.&#xD;
&#xD;
          9. Participation in other clinical trials actively testing new anti-cancer treatments,&#xD;
             unless previously written approval is provided by the Sponsor.&#xD;
&#xD;
         10. Requirement for concurrent treatment with nitrates or other drugs that may, in the&#xD;
             judgment of the treating investigator, create a risk for a precipitous decrease in&#xD;
             blood pressure.&#xD;
&#xD;
         11. Female subjects who are pregnant or breastfeeding.&#xD;
&#xD;
         12. Any other conditions that, in the Investigator's opinion, might indicate the subject&#xD;
             to be unsuitable for the study.&#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>Eugene P Kennedy, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Chief Medical Officer</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Megan Holm</last_name>
    <phone>484-615-2036</phone>
    <email>mholm@galeratx.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eugene P Kennedy, MD</last_name>
    <phone>484.870.9616</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center at NCMC</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80631</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Supriya Jain, MD</last_name>
      <phone>970-810-6690</phone>
    </contact>
    <investigator>
      <last_name>Supriya Jain, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Banner McKee Medical Center</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80538</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Supriya Jain, MD</last_name>
      <phone>970-810-6690</phone>
    </contact>
    <contact_backup>
      <last_name>Kimberly Reyna</last_name>
      <phone>970-820-5982</phone>
    </contact_backup>
    <investigator>
      <last_name>Supriya Jain, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IACT Health</name>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31903</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Douglas Ciuba, MD</last_name>
      <phone>706-596-5413</phone>
    </contact>
    <investigator>
      <last_name>Douglas Ciuba, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandy Vollstedt</last_name>
      <phone>319-353-7143</phone>
    </contact>
    <investigator>
      <last_name>Bryan Allen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48208</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heather Franklin</last_name>
      <phone>919-668-3726</phone>
    </contact>
    <contact_backup>
      <last_name>Linda Kaltenback</last_name>
      <phone>919-681-6804</phone>
    </contact_backup>
    <investigator>
      <last_name>Christopher Kelsey, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tithi Biswas, MD</last_name>
      <phone>216-844-5336</phone>
    </contact>
    <investigator>
      <last_name>Tithi Biswas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center &amp; Research Institute</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy Curtis, MD</last_name>
      <phone>864-560-6954</phone>
    </contact>
    <investigator>
      <last_name>Amy Curtis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Parkland Health and Hospital System</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hector Gonzalez</last_name>
      <email>hector.gonzalez@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Kenneth Westover, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hector Gonzalez</last_name>
      <email>hector.gonzalez@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Kenneth Westover, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Providence Regional Medical Center</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Cancer Care Northwest</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Orlan MacDonald, MD</last_name>
      <phone>509-228-1000</phone>
    </contact>
    <investigator>
      <last_name>Orlan MacDonald, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>lymph node negative NSCLC</keyword>
  <keyword>centrally located NSCLC</keyword>
  <keyword>large NSCLC</keyword>
  <keyword>SBRT</keyword>
  <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/NCT04476797
org study id: GTI-4711-101
nct id: NCT04476797
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
GTI-4711-101 is a Phase I/II study of the safety of GC4711, its effect on in-field tumor
      response and its potential to reduce radiation-related pulmonary injury due to SBRT for lymph
      node negative (T1 to T3N0M0) peripheral or central localized (within 2cm of the proximal
      bronchial tree) NSCLC.

      After an open-label, Phase 1, safety cohort of 5 subjects has been completed, a randomized,
      placebo-controlled Phase 2 portion of 66 subjects will be conducted.
Subjects must be referred for SBRT with large peripheral lesions (>1cm-7cm) and/or central
      localized, node negative, non-metastatic NSCLC, and have an ECOG PS score of 0-3. Feasibility
      of SBRT is judged by the treating physician.

      SBRT is planned for the tumor location as a dose of or 3 fractions of 18-20 Gy (Phase 2 only)
      or 5 fractions of 10-12 Gy. SBRT fractions will be given within 180 minutes from the end of
      the GC4711 or placebo infusion.

      After completion of Phase I, a Phase II, randomized, placebo-controlled study will be
      initiated, wherein approximately 66 subjects referred for SBRT with early stage large and/or
      central localized NSCLC will be randomized in a 1:1 ratio to receive either GC4711 or placebo
      given intravenously (IV) over 15 minutes before each fraction of SBRT, beginning the day of
      the first fraction of SBRT and ending the last day of SBRT.

      Subjects will be monitored for treatment emergent adverse events for 30 days post SBRT
      completion. Additionally, subjects will be monitored 90 days post-SBRT for all adverse events
      to evaluate acute toxicities, and monitored for 1-year post-SBRT completion for specific late
      toxicities.

      In-field tumor response and overall survival will be evaluated through 24 months post SBRT
      completion.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: After the open label Phase 1 portion, subjects in the Phase2 portion will be randomized in a 1:1 ratio to receive GC4711 or placebo before each fraction of SBRT
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Phase 2 is a randomized, placebo-controlled study
measure: Number of dose-limiting toxicities during treatment and within 30 days post SBRT
time frame: DLT 30 days post SBRT
description: Phase 1
measure: Percent of patients with a best RECIST response of CR or PR amongst all responses through Month 6
time frame: 6 months post SBRT
description: Phase 2
arm group label: GC4711 + SBRT
arm group type: Experimental
arm group label: Placebo + SBRT
arm group type: Placebo Comparator
intervention type: Drug
intervention name: GC4711
description: 15 minute IV Infusion prior to SBRT
arm group label: GC4711 + SBRT
intervention type: Drug
intervention name: Placebo
description: 15 minute IV infusion prior to SBRT
arm group label: Placebo + SBRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eugene P Kennedy, MD
role: Study Chair
affiliation: Chief Medical Officer
last name: Megan Holm
phone: 484-615-2036
email: mholm@galeratx.com
last name: Eugene P Kennedy, MD
phone: 484.870.9616
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No