<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/NCT03275597</url>
  </required_header>
  <id_info>
    <org_study_id>UW17003</org_study_id>
    <secondary_id>A533300</secondary_id>
    <secondary_id>SMPH\HUMAN ONCOLOGY\HUMAN ONCO</secondary_id>
    <secondary_id>NCI-2017-01952</secondary_id>
    <secondary_id>Protocol Version 10/2//2020</secondary_id>
    <secondary_id>2017-0665</secondary_id>
    <nct_id>NCT03275597</nct_id>
  </id_info>
  <brief_title>Phase Ib Study of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Non-small Lung Cancer (NSCLC) With Dual Immune Checkpoint Inhibition</brief_title>
  <official_title>Comprehensive Stereotactic Body Radiotherapy (SBRT) to All Sites of Oligometastatic Non-small Cell Lung Cancer (NSCLC) Combined With Durvalumab (MEDI4736) and Tremelimumab Dual Immune Checkpoint Inhibition.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition&#xD;
      (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of&#xD;
      oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease&#xD;
      sites followed by combination of durvalumab and tremelimumab for patients for whom the goal&#xD;
      is ablating all known sites of disease. The investigators anticipate that for many&#xD;
      participants this will be the first line-therapy. Participants who have received&#xD;
      prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior&#xD;
      immunotherapy treatment is not allowed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 20, 2018</start_date>
  <completion_date type="Actual">July 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 1, 2020</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>Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Toxicities will be summarized by type and severity in tabular format. Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival assessed with RECIST 1.1 tumor assessments</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Progression-free survival (PFS) will be defined as the difference (in months) between the date of study enrollment and the date of disease progression or death due to any cause. PFS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median PFS. PFS assessed with RECIST 1.1 tumor assessments. The effect of DCI with durvalumab and tremelimumab will be compared against historical controls for a 95% CI and p-value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival assessed with RECIST 1.1 tumor assessments</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Overall survival (OS) will be defined as the difference (in months) between the date of study enrollment to the date death due to any cause. OS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median OS. The effect of DCI with durvalumab tremelimumab will be compared against historical controls for a 95% CI and p-value.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluate immune response</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Determine whether immune response on biopsy sections or circulating tumor cells is increased following SBRT. The paired McNemar's test will be used to compare with subjects with an immune response between assessment time point.</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluate PD-L1 expression</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Determine whether PD-L1 expression on biopsy sections or circulating tumor cells is increased following SBRT. PD-L1 expression will be summarized in terms of means, standard deviation, median and range. Absolute and percentage changes in PD-L1 expression levels between the pre-SBRT versus post-SBRT assessment will be calculated and evaluated using a paired t-test.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Non-small Cell Lung Cancer Stage IV</condition>
  <arm_group>
    <arm_group_label>SBRT followed by Durvalumab+Tremelimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Therapeutic Interventions Stereotactic Body Radiotherapy (SBRT) to all sites of disease between 30 and 50 Gy in five fractions administered over two weeks.&#xD;
Investigational Product(s), Dose, and Mode of Administration: to begin 7 days (+/- 3 days) after radiation Durvalumab 1500 mg via infusion Q4W (equivalent to 20 mg/kg Q4W) until disease progression in patients &gt; 30 kg Tremelimumab 300 mg via infusion (equivalent to 4 mg/kg) in one dose in patients &gt;30 kg Weight-based dosing should be utilized for patients ≤30 kg; durvalumab 20 mg/kg Q4W and tremelimumab 4 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab is an FDA-approved immunotherapy for cancer. Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1 and is being developed by AstraZeneca/MedImmune for use in the treatment of cancer.</description>
    <arm_group_label>SBRT followed by Durvalumab+Tremelimumab</arm_group_label>
    <other_name>1428935-60-7</other_name>
    <other_name>D10808</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab</intervention_name>
    <description>Tremelimumab is a monoclonal antibody against CTLA-4. It is an IgG 2 kappa isotype mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also known as CD152 (cluster of differentiation 152). This is an immunomodulatory therapy (IMT) that is being developed by AstraZeneca for use in the treatment of cancer.</description>
    <arm_group_label>SBRT followed by Durvalumab+Tremelimumab</arm_group_label>
    <other_name>745013-59-6</other_name>
    <other_name>QEN1X95CIX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Body Radiotherapy</intervention_name>
    <description>SBRT is a highly conformal approach to the delivery of radiation therapy, maximizing radiation dose to the tumor while minimizing dose to nearby normal tissues.</description>
    <arm_group_label>SBRT followed by Durvalumab+Tremelimumab</arm_group_label>
    <other_name>SRBT</other_name>
    <other_name>stereotactic ablative radiotherapy</other_name>
    <other_name>SABR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with histologically or cytologically confirmed stage IV NSCLC not&#xD;
             amenable to curative surgery or radiation&#xD;
&#xD;
          -  Participants may have had prior chemotherapy or be chemotherapy naïve&#xD;
&#xD;
          -  Participants must have tumors that lack sensitizing EGFR mutation (e.g. exon 19&#xD;
             deletion or exon 21 L858R) or ALK rearrangement. If a participant has squamous&#xD;
             histology, then EGFR and ALK testing is not required.&#xD;
&#xD;
          -  No prior treatment with cancer immunotherapy including, but not limited to, other&#xD;
             anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 anti-&#xD;
             (PD-L2) antibodies, excluding therapeutic anticancer vaccines.&#xD;
&#xD;
          -  Participants will have 6 or less extracranial sites, which can safely receive SBRT&#xD;
             between 30 - 50 Gy in 5 fractions. A site may have multiple tumor lesions within it as&#xD;
             long as the gross tumor volume (GTV) of the site is 8 cm or less and can be covered in&#xD;
             an acceptable SBRT field determined by the PI. All gross disease must be amenable to&#xD;
             treatment with SBRT, as allowable per normal tissue constraints. Participants will not&#xD;
             have had any prior radiation therapy significantly overlapping a tumor site to be&#xD;
             treated.&#xD;
&#xD;
          -  Participants must have evaluable disease, as defined by RECIST 1.1.&#xD;
&#xD;
          -  World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance&#xD;
             status of 0 or 1 at enrollment&#xD;
&#xD;
          -  Life expectancy of &gt; 12 weeks&#xD;
&#xD;
          -  Participant is willing and able to comply with the protocol for the duration of the&#xD;
             study including undergoing treatment and scheduled visits and examinations including&#xD;
             follow up.&#xD;
&#xD;
          -  Participants with treated metastatic lesions to the brain may be enrolled after&#xD;
             completing stereotactic radiosurgery (may enroll 14 days after treatment) or whole&#xD;
             brain radiation (may enroll 14 days after treatment) and must be off corticosteroids&#xD;
             for 14 days prior to start of SBRT.&#xD;
&#xD;
          -  Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (&gt; 1500 per mm^3)&#xD;
&#xD;
               -  Platelet count ≥ 100 x 10^9/L (&gt;100,000 per mm^3)&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not&#xD;
                  apply for participants with confirmed Gilbert's syndrome, who will be allowed in&#xD;
                  consultation with their physician.&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which&#xD;
                  case ALT and AST must be ≤ 5x ULN&#xD;
&#xD;
               -  Serum creatinine &lt;1.5 x upper limit of normal (ULN) OR creatinine clearance&#xD;
                  (CrCl) ≥30 mL/min for participants with creatinine levels &gt;1.5 × institutional&#xD;
                  ULN&#xD;
&#xD;
          -  Female participant of childbearing potential should have a negative urine or serum&#xD;
             pregnancy prior to receiving the first study treatment. If the urine test is positive&#xD;
             or cannot be confirmed as negative, a serum pregnancy test will be required&#xD;
&#xD;
          -  Female participants of childbearing potential should be willing to use 1 method of&#xD;
             highly effective birth control, 2 methods of effective birth control, be surgically&#xD;
             sterile, or abstain from heterosexual activity for the course of the study through 180&#xD;
             days after the last dose of study medication. Participants of childbearing potential&#xD;
             are those who have not been surgically sterilized or have not been free from menses&#xD;
             for &gt; 1 year.&#xD;
&#xD;
          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
             age-specific requirements apply:&#xD;
&#xD;
               -  Women &lt; 50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinizing hormone and follicle- stimulating hormone&#xD;
                  levels in the post-menopausal range for the institution or underwent surgical&#xD;
                  sterilization (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
               -  Women ≥ 50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiation-induced oophorectomy with last menses &gt;1 year ago, had&#xD;
                  chemotherapy-induced menopause with &gt; 1 year interval since last menses, or&#xD;
                  underwent surgical sterilization (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
          -  Participant must be willing and able to provide written informed consent for the&#xD;
             trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site)&#xD;
&#xD;
          -  Previous enrollment in the present study&#xD;
&#xD;
          -  Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology&#xD;
&#xD;
          -  Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.&#xD;
             Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone&#xD;
             replacement therapy) is acceptable.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 14 days prior to the&#xD;
             start of study treatment.&#xD;
&#xD;
          -  Participants with untreated spinal cord compression. Participants with spinal cord&#xD;
             compression may be enrolled if stable after completing surgery (may enroll 14 days&#xD;
             after surgery) or radiation (may enroll 14 days after radiation) and must be off&#xD;
             corticosteroids for at least 14 days prior to the start of SBRT.&#xD;
&#xD;
          -  Participants with untreated brain metastasis. Participants with metastatic lesions to&#xD;
             the brain may be enrolled after completing stereotactic radiosurgery or whole brain&#xD;
             radiation (may enroll 14 days after radiation and must be off corticosteroids for at&#xD;
             least 14 days prior to the start of SBRT.&#xD;
&#xD;
          -  Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an&#xD;
             anti-CTLA4 inhibitor including tremelimumab&#xD;
&#xD;
          -  Participants with a known targetable EGFR mutation or ALK rearrangement&#xD;
&#xD;
          -  History of another primary malignancy except for:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease ≥2 years&#xD;
&#xD;
               -  Non-metastatic prostate adenocarcinoma, or treated superficial non-invasive&#xD;
                  bladder cancer&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease (eg, cervical&#xD;
                  cancer in situ)&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
          -  Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,&#xD;
             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal&#xD;
             antibodies, other investigational agent) ≤ 14 days of registration&#xD;
&#xD;
          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms.&#xD;
             Abnormality must be confirmed on 3 ECGs.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of durvalumab or tremelimumab&#xD;
&#xD;
        The following are exceptions to this criterion:&#xD;
&#xD;
          -  Intranasal, inhaled, topical steroids, or local steroid injections (eg,&#xD;
             intra-articular injection).&#xD;
&#xD;
          -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or&#xD;
             its equivalent&#xD;
&#xD;
          -  Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)&#xD;
&#xD;
          -  Active or known autoimmune disease that has required immunosuppressive systemic&#xD;
             treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids,&#xD;
             or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or&#xD;
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)&#xD;
             is not considered a form of systemic treatment and is allowed. The following are&#xD;
             exceptions to this criterion:&#xD;
&#xD;
               -  Participants with vitiligo or alopecia,&#xD;
&#xD;
               -  Grave's disease,&#xD;
&#xD;
               -  Hypothyroidism (eg, following Hashimoto syndrome),&#xD;
&#xD;
               -  Psoriasis not requiring systemic treatment (within the past 2 years)&#xD;
&#xD;
               -  Participants with celiac disease controlled by diet alone&#xD;
&#xD;
                    -  History of active primary immunodeficiency&#xD;
&#xD;
                    -  History of allogeneic organ transplant&#xD;
&#xD;
                    -  Active infection, including tuberculosis (clinical evaluation), hepatitis B,&#xD;
                       hepatitis C, or human immunodeficiency virus (HIV, positive HIV 1 or 2&#xD;
                       antibodies). Active hepatitis B virus (HBV) is defined by a known positive&#xD;
                       HBV surface antigen (HBsAg) result. Participants with a past or resolved HBV&#xD;
                       infection (defined as the presence of hepatitis B core antibody and absence&#xD;
                       of HBsAg) are eligible. Participants positive for hepatitis C virus (HCV)&#xD;
                       antibody are eligible only if polymerase chain reaction is negative for HCV&#xD;
                       ribonucleic acid (RNA).&#xD;
&#xD;
                    -  History of leptomeningeal carcinomatosis&#xD;
&#xD;
                    -  Receipt of live attenuated vaccination within 30 days prior to the first&#xD;
                       dose of IP. Note: Participants, if enrolled, should not receive live vaccine&#xD;
                       during the study and up to 30 days after the last dose of IP.&#xD;
&#xD;
                    -  Any condition or uncontrolled intercurrent illness that, in the opinion of&#xD;
                       the Investigator, would interfere with the evaluation of IP or&#xD;
                       interpretation of patient safety or study results, including, but not&#xD;
                       limited to, ongoing or active infection, symptomatic congestive heart&#xD;
                       failure, uncontrolled hypertension, unstable angina pectoris, cardiac&#xD;
                       arrhythmia, or psychiatric illness/social situations that would limit&#xD;
                       compliance with study requirement, substantially increase risk of incurring&#xD;
                       AEs from durvalumab or tremelimumab, or compromise the ability of the&#xD;
                       patient to give written informed consent&#xD;
&#xD;
                    -  Subjects with uncontrolled seizures.&#xD;
&#xD;
                    -  Female participants who are pregnant or breast-feeding or male or female&#xD;
                       patients of reproductive potential who are not willing to employ effective&#xD;
                       birth control from screening to 180 days after the last dose of durvalumab&#xD;
                       and tremelimumab combination therapy or 90 days after the last dose of&#xD;
                       durvalumab monotherapy.&#xD;
&#xD;
                    -  History of hypersensitivity to IP or comparator agents&#xD;
&#xD;
                    -  History of medically diagnosed pneumonitis or interstitial lung disease&#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>Michael Bassetti, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.uwhealth.org/uw-carbone-cancer-center/47424</url>
    <description>UW Carbone Cancer Center home page</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03275597
org study id: UW17003
secondary id: A533300
secondary id: SMPH\HUMAN ONCOLOGY\HUMAN ONCO
secondary id: NCI-2017-01952
secondary id: Protocol Version 10/2//2020
secondary id: 2017-0665
nct id: NCT03275597
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition
      (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of
      oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease
      sites followed by combination of durvalumab and tremelimumab for patients for whom the goal
      is ablating all known sites of disease. The investigators anticipate that for many
      participants this will be the first line-therapy. Participants who have received
      prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior
      immunotherapy treatment is not allowed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03
time frame: Up to 3 years
description: Toxicities will be summarized by type and severity in tabular format. Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.
measure: Progression Free Survival assessed with RECIST 1.1 tumor assessments
time frame: Up to 4 years
description: Progression-free survival (PFS) will be defined as the difference (in months) between the date of study enrollment and the date of disease progression or death due to any cause. PFS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median PFS. PFS assessed with RECIST 1.1 tumor assessments. The effect of DCI with durvalumab and tremelimumab will be compared against historical controls for a 95% CI and p-value.
measure: Overall Survival assessed with RECIST 1.1 tumor assessments
time frame: Up to 4 years
description: Overall survival (OS) will be defined as the difference (in months) between the date of study enrollment to the date death due to any cause. OS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median OS. The effect of DCI with durvalumab tremelimumab will be compared against historical controls for a 95% CI and p-value.
measure: Evaluate immune response
time frame: Up to 4 years
description: Determine whether immune response on biopsy sections or circulating tumor cells is increased following SBRT. The paired McNemar's test will be used to compare with subjects with an immune response between assessment time point.
measure: Evaluate PD-L1 expression
time frame: Up to 4 years
description: Determine whether PD-L1 expression on biopsy sections or circulating tumor cells is increased following SBRT. PD-L1 expression will be summarized in terms of means, standard deviation, median and range. Absolute and percentage changes in PD-L1 expression levels between the pre-SBRT versus post-SBRT assessment will be calculated and evaluated using a paired t-test.
arm group label: SBRT followed by Durvalumab+Tremelimumab
arm group type: Experimental
description: Therapeutic Interventions Stereotactic Body Radiotherapy (SBRT) to all sites of disease between 30 and 50 Gy in five fractions administered over two weeks.
Investigational Product(s), Dose, and Mode of Administration: to begin 7 days (+/- 3 days) after radiation Durvalumab 1500 mg via infusion Q4W (equivalent to 20 mg/kg Q4W) until disease progression in patients > 30 kg Tremelimumab 300 mg via infusion (equivalent to 4 mg/kg) in one dose in patients >30 kg Weight-based dosing should be utilized for patients ≤30 kg; durvalumab 20 mg/kg Q4W and tremelimumab 4 mg/kg
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab is an FDA-approved immunotherapy for cancer. Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1 and is being developed by AstraZeneca/MedImmune for use in the treatment of cancer.
arm group label: SBRT followed by Durvalumab+Tremelimumab
other name: 1428935-60-7
other name: D10808
intervention type: Drug
intervention name: Tremelimumab
description: Tremelimumab is a monoclonal antibody against CTLA-4. It is an IgG 2 kappa isotype mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also known as CD152 (cluster of differentiation 152). This is an immunomodulatory therapy (IMT) that is being developed by AstraZeneca for use in the treatment of cancer.
arm group label: SBRT followed by Durvalumab+Tremelimumab
other name: 745013-59-6
other name: QEN1X95CIX
intervention type: Radiation
intervention name: Stereotactic Body Radiotherapy
description: SBRT is a highly conformal approach to the delivery of radiation therapy, maximizing radiation dose to the tumor while minimizing dose to nearby normal tissues.
arm group label: SBRT followed by Durvalumab+Tremelimumab
other name: SRBT
other name: stereotactic ablative radiotherapy
other name: SABR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Bassetti, MD, PhD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
url: http://www.uwhealth.org/uw-carbone-cancer-center/47424
description: UW Carbone Cancer Center home page
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Durvalumab
mesh term: Tremelimumab