<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/NCT03818776</url>
  </required_header>
  <id_info>
    <org_study_id>CASE1518</org_study_id>
    <nct_id>NCT03818776</nct_id>
  </id_info>
  <brief_title>Proton Based Cardiac Sparing Accelerated Fractionated RadioTherapy in Unresectable NSCLC</brief_title>
  <official_title>A Pilot Trial of Proton Based Cardiac Sparing Accelerated Fractionated RadioTherapy in Unresectable Non-Small Cell Lung Cancer With Extended Durvalumab Therapy (PARTICLE-D)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Case Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Case Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to treat participants with the combination of durvalumab (the&#xD;
      study drug) and proton beam therapy. Proton beam therapy is a type of radiotherapy (RT) with&#xD;
      a unique characteristic where the proton stops at a specific depth according to its energy.&#xD;
      This may be advantageous in treating lung cancer because it allows for a sufficient tumor&#xD;
      dose that may improve local control and survival while sparing normal organs at risk, such as&#xD;
      the heart, lung, and spinal cord.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All study participants will receive the same study intervention, which will consist of proton&#xD;
      based external beam radiation therapy with concurrent Durvalumab starting one week before RT.&#xD;
      Radiation will be delivered using cardiac sparing accelerated fractionated proton radiation.&#xD;
      Radiation will have two dose escalation schemes followed by an expansion cohort for a total&#xD;
      of approximately 24 participants enrolled at University Hospitals Cleveland Medical Center.&#xD;
&#xD;
      The objectives of this study are to evaluate the safety and feasibility of combination of&#xD;
      durvalumab with two different schemes for accelerated fractionation proton radiation in&#xD;
      participants who are unable to tolerate concurrent chemoradiation therapy. This will also&#xD;
      include the evaluation of adverse events resulting from these treatment schemes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2019</start_date>
  <completion_date type="Actual">January 27, 2022</completion_date>
  <primary_completion_date type="Actual">January 27, 2022</primary_completion_date>
  <phase>Early Phase 1</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>Arm 1: 60 CGyE in 20 fractions (3+3 participants, 3-6 total) Arm 2: 69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of intervention as defined by number of participants with Dose Limiting Toxicities (DLT) between first dose of Durvalumab and 30 days following completion of radiotherapy.</measure>
    <time_frame>Up to 30 days following end of treatment</time_frame>
    <description>Safety of intervention as defined by number of participants with DLT's between first dose of Durvalumab and 30 days following completion of radiotherapy. This is defined as 0 of 3 or 1 of 6 participants having no DLT of either Durvalumab or RT.&#xD;
DLT for RT defined as:&#xD;
Grade 4-5 non-hematologic serious adverse events (SAEs) considered by the Investigators to be probably or definitely related to protocol treatment.&#xD;
Grade 3 or higher cardiac adverse events (e.g. severely symptomatic congestive heart failure (CHF), myocarditis, pericardial effusion, myocardial infarction, symptomatic arrhythmia) considered by the Investigators to be probably or definitely related to protocol treatment.&#xD;
Grade 3 or higher pulmonary adverse events (e.g. dyspnea/pneumonitis) considered by the Investigators to be probably or definitely related to protocol treatment and not responsive to steroids.&#xD;
Failure to receive at least 54</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility of intervention defined by number of participants receiving full course of RT treatment and minimum of two doses of Durvalumab</measure>
    <time_frame>Up to 30 days following end of treatment</time_frame>
    <description>Feasibility of intervention is defined as a participant receiving the entire course of prescribed RT as well as having received a minimum of two doses of Durvalumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with Adverse Events according to CTCAE v5.0</measure>
    <time_frame>Up to 30 days following end of treatment</time_frame>
    <description>All toxicities will be graded according to NCI CTCAE, Version 5.0. See Adverse Events section.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1 - 60 CGyE in 20 fractions</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT.&#xD;
Radiation will follow dose escalation scheme:&#xD;
60 CGyE in 20 fractions (3+3 participants, 3-6 total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT.&#xD;
Radiation will follow dose escalation scheme:&#xD;
69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody immunotherapy for lung cancer. Participants will receive 1500mg durvalumab via intravenous (IV) infusion Q4W for up to a maximum of 12 months (up to 13 doses/cycles) with the last administration on week 48 unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. (N.b. If a participant's weight falls to 30kg (≤30 kg)), then the participant should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W after consultation between Investigator and Study Physician, until the weight improves to above 30 kg &gt;30 kg, at which point the participant should start receiving the fixed dosing of durvalumab 1500 mg Q4W).</description>
    <arm_group_label>Arm 1 - 60 CGyE in 20 fractions</arm_group_label>
    <arm_group_label>Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton beam therapy RT</intervention_name>
    <description>Proton beam therapy is a type of RT where the proton stops at a specific depth according to its energy which allows for a sufficient tumor dose that may improve local control and survival while sparing normal organs at risk, such as the heart, lung, and spinal cord.</description>
    <arm_group_label>Arm 1 - 60 CGyE in 20 fractions</arm_group_label>
    <arm_group_label>Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Body Weight &gt;30kg&#xD;
&#xD;
          -  Must have anticipated life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Must be histologically or cytologically confirmed to be non-small cell lung cancer&#xD;
             (NSCLC) confirmed by biopsy within 90 days of registration.&#xD;
&#xD;
          -  Any tumor PD-L1 expression is allowed (including 0% to 100%, or unknown at time of&#xD;
             study enrollment)&#xD;
&#xD;
          -  AJCC 8th Stage IIA-IIIC.&#xD;
&#xD;
          -  Must be deemed by Specialist or tumor board decision to not be a candidate for&#xD;
             surgical resection or the participant refuses resection. Being deemed unresectable can&#xD;
             be for any reason, including but not limited to: tumor location, tumor&#xD;
             characteristics, operative risks, poor participant lung function, participant age or&#xD;
             medical comorbidity.&#xD;
&#xD;
          -  Must be deemed by Medical Oncologist or tumor board decision to not be a candidate for&#xD;
             or able to tolerate standard cisplatinum based doublet concurrent chemoradiation&#xD;
             therapy or the participant refuses chemotherapy. Being deemed not a chemotherapy&#xD;
             candidate can be for any reason, including but not limited to: age, medical&#xD;
             comorbidity, end organ dysfunction.&#xD;
&#xD;
          -  Pulmonary function testing performed within 365 days prior to registration. .&#xD;
             Sufficient lung function as judged by the primary investigator based on anticipated&#xD;
             radiation fields, with a minimum of FEV1 ≥ 0.7 Liter or ≥ 30% and DLCO ≥ 30% with or&#xD;
             without bronchodilator within 365 days prior to registration.&#xD;
&#xD;
          -  Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
          -  Haemoglobin ≥9.0 g/dL&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) 1.5 (or 1.0) x (&gt; 1500 per mm3)&#xD;
&#xD;
          -  Platelet count ≥75 x 109/L (&gt;75,000 per mm3)&#xD;
&#xD;
          -  Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply&#xD;
             to participants with confirmed Gilbert's syndrome (persistent or recurrent&#xD;
             hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or&#xD;
             hepatic pathology), who will be allowed only in consultation with their physician.&#xD;
&#xD;
          -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal&#xD;
&#xD;
          -  Measured creatinine clearance (CL) &gt;30 mL/min or Calculated creatinine CL&gt;30 mL/min by&#xD;
             the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection&#xD;
             for determination of creatinine clearance:&#xD;
&#xD;
          -  Males:&#xD;
&#xD;
        Creatinine CL (mL/min) = (Weight (kg) x (140 - Age)) / (72 x serum creatinine (mg/dL))&#xD;
&#xD;
          -  Females:&#xD;
&#xD;
        Creatinine CL (mL/min) = (Weight (kg) x (140 - Age)) / (72 x serum creatinine (mg/dL)) x&#xD;
        0.85&#xD;
&#xD;
          -  Subjects must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal participants. Women will be considered post-menopausal if they&#xD;
             have been amenorrheic for 12 months without an alternative medical cause. The&#xD;
             following 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 treatments&#xD;
             and if they have luteinizing hormone and follicle-stimulating hormone levels in the&#xD;
             post-menopausal range for the institution or underwent surgical sterilization&#xD;
             (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 menopause with last menses &gt;1 year ago, had&#xD;
             chemotherapy-induced menopause with last menses &gt;1 year ago, or underwent surgical&#xD;
             sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).&#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;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior large field thoracic radiation therapy is not allowed except for at the&#xD;
             discretion of the primary investigator. Prior SBRT to contralateral lung, or breast&#xD;
             radiation greater than 3 years prior is allowed. Other prior thoracic radiation is&#xD;
             allowed at the discretion of the primary investigator.&#xD;
&#xD;
          -  Prior radiation therapy, or immunotherapy for current diagnosis of NSCLC&#xD;
&#xD;
          -  Concurrent enrolment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or during the follow-up period of an&#xD;
             interventional study&#xD;
&#xD;
          -  Female participants who are pregnant or breastfeeding or male or female participants&#xD;
             of reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 90 days after the last dose of durvalumab monotherapy.&#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;
             before the first dose of IP and of low potential risk for recurrence&#xD;
&#xD;
          -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of&#xD;
             disease&#xD;
&#xD;
          -  Adequately treated carcinoma in situ (i.e. breast) without evidence of disease&#xD;
&#xD;
          -  Low risk prostate cancer which has been treated or is undergoing active surveillance.&#xD;
&#xD;
          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria&#xD;
&#xD;
          -  Participants with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after&#xD;
             consultation with the Study Physician.&#xD;
&#xD;
          -  Participants with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
             treatment with durvalumab may be included only after consultation with the Study&#xD;
             Physician.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP.&#xD;
&#xD;
          -  Judgment by the investigator that the participant is unsuitable to participate in the&#xD;
             study and the participant is unlikely to comply with study procedures, restrictions&#xD;
             and requirements&#xD;
&#xD;
        Medication Specific Exclusion Criterion:&#xD;
&#xD;
          -  History of primary immunodeficiency&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with&#xD;
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,&#xD;
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
          -  Participants with vitiligo or alopecia&#xD;
&#xD;
          -  Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on&#xD;
             hormone replacement&#xD;
&#xD;
          -  Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
          -  Participants without active disease in the last 5 years may be included but only after&#xD;
             consultation with the study physician&#xD;
&#xD;
          -  Participants with celiac disease controlled by diet alone&#xD;
&#xD;
          -  Participants with prior allogeneic bone marrow transplantation or prior solid organ&#xD;
             transplantation&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications (including but not limited to&#xD;
             prednisone &gt; 10 mg daily, cyclophosphamide, azathioprine, methotrexate, thalidomide,&#xD;
             and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1.&#xD;
             However, the use of inhaled corticosteroids and mineralocorticoids (e.g.,&#xD;
             fludrocortisone) for participants with orthostatic hypotension or adrenocortical&#xD;
             insufficiency is allowed.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic&#xD;
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirement, substantially increase&#xD;
             risk of incurring AEs or compromise the ability of the participant to give written&#xD;
             informed consent&#xD;
&#xD;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings, and tuberculosis testing in&#xD;
             line with local practice), hepatitis B (known positive hepatitis B surface antigen&#xD;
             [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive human&#xD;
             immunodeficiency virus [HIV] 1/2 antibodies). Participants with a past or resolved&#xD;
             hepatitis B (HBV) infection (defined as the presence of hepatitis B core antibody&#xD;
             [anti-HBc] and absence of HBsAg) are eligible. Participants positive for hepatitis C&#xD;
             (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:&#xD;
             Participants, if enrolled, should not receive live vaccine whilst receiving IP and up&#xD;
             to 30 days after the last dose of IP.&#xD;
&#xD;
          -  Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical&#xD;
             study regardless of treatment arm assignment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Debora Bruno, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Durvalumab</keyword>
  <keyword>PARTICLE-D</keyword>
  <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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Beginning 3 months and ending 5 years following article publication</ipd_time_frame>
    <ipd_access_criteria>Will be shared with researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. To gain access, data requesters will need to sign a data access agreement</ipd_access_criteria>
  </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/NCT03818776
org study id: CASE1518
nct id: NCT03818776
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
The purpose of this study is to treat participants with the combination of durvalumab (the
      study drug) and proton beam therapy. Proton beam therapy is a type of radiotherapy (RT) with
      a unique characteristic where the proton stops at a specific depth according to its energy.
      This may be advantageous in treating lung cancer because it allows for a sufficient tumor
      dose that may improve local control and survival while sparing normal organs at risk, such as
      the heart, lung, and spinal cord.
All study participants will receive the same study intervention, which will consist of proton
      based external beam radiation therapy with concurrent Durvalumab starting one week before RT.
      Radiation will be delivered using cardiac sparing accelerated fractionated proton radiation.
      Radiation will have two dose escalation schemes followed by an expansion cohort for a total
      of approximately 24 participants enrolled at University Hospitals Cleveland Medical Center.

      The objectives of this study are to evaluate the safety and feasibility of combination of
      durvalumab with two different schemes for accelerated fractionation proton radiation in
      participants who are unable to tolerate concurrent chemoradiation therapy. This will also
      include the evaluation of adverse events resulting from these treatment schemes.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Arm 1: 60 CGyE in 20 fractions (3+3 participants, 3-6 total) Arm 2: 69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of intervention as defined by number of participants with Dose Limiting Toxicities (DLT) between first dose of Durvalumab and 30 days following completion of radiotherapy.
time frame: Up to 30 days following end of treatment
description: Safety of intervention as defined by number of participants with DLT's between first dose of Durvalumab and 30 days following completion of radiotherapy. This is defined as 0 of 3 or 1 of 6 participants having no DLT of either Durvalumab or RT.
DLT for RT defined as:
Grade 4-5 non-hematologic serious adverse events (SAEs) considered by the Investigators to be probably or definitely related to protocol treatment.
Grade 3 or higher cardiac adverse events (e.g. severely symptomatic congestive heart failure (CHF), myocarditis, pericardial effusion, myocardial infarction, symptomatic arrhythmia) considered by the Investigators to be probably or definitely related to protocol treatment.
Grade 3 or higher pulmonary adverse events (e.g. dyspnea/pneumonitis) considered by the Investigators to be probably or definitely related to protocol treatment and not responsive to steroids.
Failure to receive at least 54
measure: Feasibility of intervention defined by number of participants receiving full course of RT treatment and minimum of two doses of Durvalumab
time frame: Up to 30 days following end of treatment
description: Feasibility of intervention is defined as a participant receiving the entire course of prescribed RT as well as having received a minimum of two doses of Durvalumab.
measure: Number of participants with Adverse Events according to CTCAE v5.0
time frame: Up to 30 days following end of treatment
description: All toxicities will be graded according to NCI CTCAE, Version 5.0. See Adverse Events section.
arm group label: Arm 1 - 60 CGyE in 20 fractions
arm group type: Experimental
description: Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT.
Radiation will follow dose escalation scheme:
60 CGyE in 20 fractions (3+3 participants, 3-6 total)
arm group label: Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a
arm group type: Experimental
description: Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT.
Radiation will follow dose escalation scheme:
69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody immunotherapy for lung cancer. Participants will receive 1500mg durvalumab via intravenous (IV) infusion Q4W for up to a maximum of 12 months (up to 13 doses/cycles) with the last administration on week 48 unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. (N.b. If a participant's weight falls to 30kg (≤30 kg)), then the participant should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W after consultation between Investigator and Study Physician, until the weight improves to above 30 kg >30 kg, at which point the participant should start receiving the fixed dosing of durvalumab 1500 mg Q4W).
arm group label: Arm 1 - 60 CGyE in 20 fractions
arm group label: Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a
other name: MEDI4736
intervention type: Radiation
intervention name: Proton beam therapy RT
description: Proton beam therapy is a type of RT where the proton stops at a specific depth according to its energy which allows for a sufficient tumor dose that may improve local control and survival while sparing normal organs at risk, such as the heart, lung, and spinal cord.
arm group label: Arm 1 - 60 CGyE in 20 fractions
arm group label: Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Debora Bruno, MD
role: Principal Investigator
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Durvalumab
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Beginning 3 months and ending 5 years following article publication
ipd access criteria: Will be shared with researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. To gain access, data requesters will need to sign a data access agreement