<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/NCT03307759</url>
  </required_header>
  <id_info>
    <org_study_id>SABRseq</org_study_id>
    <nct_id>NCT03307759</nct_id>
  </id_info>
  <brief_title>Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma</brief_title>
  <acronym>SABRseq</acronym>
  <official_title>Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peter MacCallum Cancer Centre, Australia</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This investigator driven Phase Ib study will examine the safety, efficacy and biological&#xD;
      effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell&#xD;
      death 1 (PD-1), which will be given either before or after stereotactic ablative body&#xD;
      radiotherapy (SABR) for metastatic NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2022</primary_completion_date>
  <phase>Phase 1</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>Adverse events measured using CTCAE version 4.03</measure>
    <time_frame>Up to 24 months after commencement of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response assessed using RECIST 1.1</measure>
    <time_frame>Assessed at 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response assessed using irRECIST</measure>
    <time_frame>Assessed at 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response assessed using PERCIST1.0</measure>
    <time_frame>Assessed at 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response assessed using Peter Mac Metabolic Response Criteria</measure>
    <time_frame>Assessed at 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From randomisation until the date of death from any cause assessed up to the date when the last patient has their 24 months assessment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From randomisation until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 24 months assessment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>SABR plus pembrolizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>SABR followed by pembrolizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab plus SABR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pembrolizumab followed by SABR after cycle 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab</description>
    <arm_group_label>Pembrolizumab plus SABR</arm_group_label>
    <arm_group_label>SABR plus pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy (SABR)</intervention_name>
    <description>Radiotherapy</description>
    <arm_group_label>Pembrolizumab plus SABR</arm_group_label>
    <arm_group_label>SABR plus pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have provided written informed consent for the trial.&#xD;
&#xD;
          2. Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          3. Have at least one lesion not planned for SABR that is measurable disease based on&#xD;
             RECIST 1.1.&#xD;
&#xD;
          4. Patients must have a histologically or cytologically confirmed metastatic non-small&#xD;
             cell lung cancer.&#xD;
&#xD;
          5. Patients with disease previously untreated with systemic therapy must have ≥ 50% PD-L1&#xD;
             staining and patients who have previously received systemic therapy must have ≥ 1%&#xD;
             PD-L1 staining on immunohistochemistry&#xD;
&#xD;
          6. Patients must have at least 1-3 lesions suitable for treatment with stereotactic&#xD;
             radiotherapy.&#xD;
&#xD;
          7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a&#xD;
             tumour lesion where feasible. Newly-obtained is defined as a specimen obtained up to&#xD;
             12 weeks prior to randomisation. Patients for whom newly-obtained samples cannot be&#xD;
             provided (e.g. inaccessible or patient safety concern) may submit an archived specimen&#xD;
             only upon agreement from the study principal investigators.&#xD;
&#xD;
          8. Have a performance status of 0-1 on the ECOG Performance Scale (see Appendix 1).&#xD;
&#xD;
          9. Demonstrate adequate organ function as defined in table 3 below, all screening labs&#xD;
             should be performed within 10 days of randomisation.&#xD;
&#xD;
             Table 3 Adequate Organ Function Laboratory Values&#xD;
&#xD;
             Absolute neutrophil count (ANC) ≥1.5x109/L Platelets≥100x109L Haemoglobin ≥90 g/L&#xD;
             without transfusion or EPO dependency (within 7 days of assessment)&#xD;
&#xD;
             Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used&#xD;
             in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥30 mL/min for&#xD;
             patients with creatinine levels &gt; 1.5 X institutional ULN&#xD;
&#xD;
             Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total&#xD;
             bilirubin levels &gt; 1.5 ULN AST (SGOT) and ALT (SGPT)≤ 2.5 X ULN OR ≤ 5 X ULN for&#xD;
             patients with liver metastases&#xD;
&#xD;
             International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial&#xD;
             Thromboplastin Time (aPTT) ≤1.5 X ULN unless patient is receiving anticoagulant&#xD;
             therapy as long as PT or PTT is within therapeutic range of intended use of&#xD;
             anticoagulants ≤1.5 X ULN unless patient is receiving anticoagulant therapy as long as&#xD;
             PT or PTT is within therapeutic range of intended use of anticoagulants&#xD;
&#xD;
         10. Life expectancy &gt; 3 months.&#xD;
&#xD;
         11. Be willing and able to comply with all study requirements, including treatment,&#xD;
             attending assessments and follow-up.&#xD;
&#xD;
         12. Female patient of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 7 days of randomisation. If the urine test is positive or cannot be&#xD;
             confirmed as negative, a serum pregnancy test will be required.&#xD;
&#xD;
         13. Female patients of childbearing potential should be willing to use 2 methods of birth&#xD;
             control or be surgically sterile, or abstain from heterosexual activity for the course&#xD;
             of the study through 120 days after the last dose of study medication (See Section&#xD;
             8.10). Patients of childbearing potential are those who have not been surgically&#xD;
             sterilized or have not been free from menses for &gt; 1 year.&#xD;
&#xD;
         14. Male patients should agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 120 days after the last dose of study therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has had previous high dose radiotherapy (biological equivalent of &gt;30Gy in 10#) to an&#xD;
             area to be treated which includes vertebral bodies (see below).&#xD;
&#xD;
             Note: Previous high dose radiotherapy is defined as a biological equivalent dose to&#xD;
             above that of 30 Gy in 10 fractions using an alpha/beta ratio (50) of 3.&#xD;
&#xD;
             Where a patient has received radiotherapy to an equivalent or lower dose than defined&#xD;
             above, stereotactic radiotherapy of the area may be considered. In doing so,&#xD;
             assessment of the volume and total dose received by any overlap region must be made,&#xD;
             and documented by generating a cumulative plan incorporating both the previous and&#xD;
             current treatment fields. It is the treating radiation oncologist's responsibility to&#xD;
             review both the current plan and the cumulative plan inclusive of previous&#xD;
             radiotherapy.&#xD;
&#xD;
          2. Has had previous thoracic radiotherapy of &gt; 36Gy within the 6 months prior to&#xD;
             randomisation.&#xD;
&#xD;
          3. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Patients with small asymptomatic or previously treated brain metastases&#xD;
             may participate provided they are stable (without evidence of progression by imaging&#xD;
             for at least four weeks prior to the first dose of trial treatment and any neurologic&#xD;
             symptoms have returned to baseline), have no evidence of enlarging brain metastases,&#xD;
             and are not using steroids for intracranial neurological symptoms at least 7 days&#xD;
             prior to trial randomisation. This exception does not include leptomeningeal disease&#xD;
             which is excluded regardless of clinical stability.&#xD;
&#xD;
          4. Has evidence of Spinal Cord Compression.&#xD;
&#xD;
          5. Has a Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a&#xD;
             neurosurgical service and considered stable (see Appendix 2).&#xD;
&#xD;
          6. Requires surgical fixation of bone lesion for stability. All surgical fixation and&#xD;
             instrumentation must be completed before randomisation on study.&#xD;
&#xD;
          7. Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 4 weeks of randomisation.&#xD;
&#xD;
          8. Has a diagnosis of immunodeficiency.&#xD;
&#xD;
          9. Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
         10. Has a hypersensitivity to pembrolizumab or any of its excipients.&#xD;
&#xD;
         11. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to&#xD;
             randomisation or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse&#xD;
             events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
         12. Has diagnosed and/or treated additional malignancy within 5 years prior to&#xD;
             randomisation with the exception of: curatively treated basal cell carcinoma of the&#xD;
             skin, squamous cell carcinoma of the skin, curatively treated early stage cervical&#xD;
             cancer, breast cancer or prostate cancer with no evidence of active disease. Other&#xD;
             exceptions may be considered following consultation with the principal investigator&#xD;
&#xD;
         13. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
         14. Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
         15. Has had any systemic anti-cancer therapy or radiation therapy within 4 weeks prior to&#xD;
             randomisation&#xD;
&#xD;
         16. Has known interstitial lung disease&#xD;
&#xD;
         17. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         18. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the patient's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the patient to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         19. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
         21. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         22. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
         23. Has received a live vaccine within 30 days of randomisation. Note: Seasonal influenza&#xD;
             vaccines for injection are generally inactivated flu vaccines and are allowed; however&#xD;
             intranasal influenza vaccines (e.g., Flu- Mist®) are live attenuated vaccines, and are&#xD;
             not allowed. -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>May 23, 2022</last_update_submitted>
  <last_update_submitted_qc>May 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 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>
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_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/NCT03307759
org study id: SABRseq
nct id: NCT03307759
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This investigator driven Phase Ib study will examine the safety, efficacy and biological
      effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell
      death 1 (PD-1), which will be given either before or after stereotactic ablative body
      radiotherapy (SABR) for metastatic NSCLC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events measured using CTCAE version 4.03
time frame: Up to 24 months after commencement of treatment
measure: Overall response assessed using RECIST 1.1
time frame: Assessed at 6 and 12 months
measure: Overall response assessed using irRECIST
time frame: Assessed at 6 and 12 months
measure: Overall response assessed using PERCIST1.0
time frame: Assessed at 6 and 12 months
measure: Overall response assessed using Peter Mac Metabolic Response Criteria
time frame: Assessed at 6 and 12 months
measure: Overall survival
time frame: From randomisation until the date of death from any cause assessed up to the date when the last patient has their 24 months assessment
measure: Progression free survival (PFS)
time frame: From randomisation until the date of first progression or until the date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 24 months assessment
arm group label: SABR plus pembrolizumab
arm group type: Active Comparator
description: SABR followed by pembrolizumab
arm group label: Pembrolizumab plus SABR
arm group type: Active Comparator
description: Pembrolizumab followed by SABR after cycle 1
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab
arm group label: Pembrolizumab plus SABR
arm group label: SABR plus pembrolizumab
intervention type: Radiation
intervention name: Radiotherapy (SABR)
description: Radiotherapy
arm group label: Pembrolizumab plus SABR
arm group label: SABR plus pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Australia
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Lung Neoplasms
mesh term: Pembrolizumab
sharing ipd: No