<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/NCT04470674</url>
  </required_header>
  <id_info>
    <org_study_id>HCRN LUN17-126</org_study_id>
    <nct_id>NCT04470674</nct_id>
  </id_info>
  <brief_title>Study of Durvalumab or Durvalumab Plus Chemotherapy in Kras Mutation Positive and PD-L1 High (≥ 50%) NSCLC Patients</brief_title>
  <official_title>Randomized Phase II Study of Durvalumab or Durvalumab Plus Chemotherapy in Kras Mutation Positive and PD-L1 High (≥ 50%) NSCLC Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shirish M Gadgeel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Henry Ford Health System</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoosier Cancer Research Network</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 is a two arm, randomized, phase II study of patients with advanced KRAS mutation&#xD;
      positive and PD-L1 high NSCLC who have not received therapy for advanced stage disease.&#xD;
      Patients will be randomized between Arm A and Arm B treatment. Arm A treatment will consist&#xD;
      of durvalumab every 4 weeks for 13 cycles. Arm B treatment will consist of durvalumab with&#xD;
      chemotherapy every 3 weeks for 4 cycles followed by durvalumab with pemetrexed every 3 weeks&#xD;
      for 13 cycles.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">April 6, 2021</start_date>
  <completion_date type="Actual">June 8, 2021</completion_date>
  <primary_completion_date type="Actual">June 8, 2021</primary_completion_date>
  <phase>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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response Rate</measure>
    <time_frame>12 months</time_frame>
    <description>Assess response rate by RECIST criteria 1.1 in Arm A and Arm B in advanced Kras mutation positive and PD-L1 high (≥50%) NSCLC patients.The objective response rate is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>12 months</time_frame>
    <description>A measurement from the date of randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>Adverse events will be summarized by frequency and severity using CTCAE version 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>12 months</time_frame>
    <description>Overall survival is defined by the date of randomization to date of death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lung Cancer</condition>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>PD-L1 Gene Mutation</condition>
  <condition>KRAS Activating Mutation</condition>
  <arm_group>
    <arm_group_label>Arm A (Durvalumab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Durvalumab 1500 mg IV every 4 weeks for 13 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (Durvalumab plus chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab 1500 mg IV plus carboplatin AUC 5 IV and pemetrexed 500 mg/m2 IV every 3 weeks for 4 cycles followed by durvalumab and pemetrexed every 3 weeks for 13 more cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab 1500 mg</description>
    <arm_group_label>Arm A (Durvalumab)</arm_group_label>
    <arm_group_label>Arm B (Durvalumab plus chemotherapy)</arm_group_label>
    <other_name>IMFINZI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>carboplatin AUC 5</description>
    <arm_group_label>Arm B (Durvalumab plus chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>pemetrexed 500 mg/m2</description>
    <arm_group_label>Arm B (Durvalumab plus chemotherapy)</arm_group_label>
    <other_name>Alimta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Written informed consent and HIPAA authorization for release of personal health&#xD;
             information. NOTE: HIPAA authorization may be included in the informed consent or&#xD;
             obtained separately.&#xD;
&#xD;
          -  Age ≥ 18 years at the time of consent.&#xD;
&#xD;
          -  Body weight &gt; 30 kg. If body weight falls to 30 kg or below during the study, the&#xD;
             subject will be removed from study drugs.&#xD;
&#xD;
          -  ECOG Performance Status of 0-1 within 7 days prior to registration.&#xD;
&#xD;
          -  Life expectancy of ≥ 12 weeks.&#xD;
&#xD;
          -  Histological or cytological evidence of stage IV Kras mutation positive non-squamous&#xD;
             NSCLC.&#xD;
&#xD;
          -  Patients who have recurrence following treatment for earlier stages of NSCLC are&#xD;
             eligible provided the recurrence has not occurred within 12 months of completing prior&#xD;
             therapy.&#xD;
&#xD;
          -  Patient's tumor must be known to be PD-L1 high (≥ 50%). SP-142 assay will not be&#xD;
             accepted. See Section 8.1 for additional information regarding this result.&#xD;
&#xD;
          -  Measurable disease according to RECIST v1.1 criteria within 4 weeks of study&#xD;
             registration.&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined in the table below; all screening labs&#xD;
             to be obtained within 14 days prior to registration.&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≥ 9.0 g/dL&#xD;
&#xD;
               -  Platelets ≥ 75 k/mm3&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 45 cc/min using the Cockcroft-Gault formula&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 × upper limit of normal (ULN) This will not apply to subjects&#xD;
                  with clinical diagnosis of Gilbert's syndrome (persistent or recurrent&#xD;
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis&#xD;
                  or hepatic pathology)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) ≤ 2.5 × ULN, unless patients has liver&#xD;
                  metastases in which case it must be ≤5 × ULN&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN, unless patients has liver metastases&#xD;
                  in which case it must be ≤5 × ULN&#xD;
&#xD;
          -  Evidence of post-menopausal status or negative urine or serum pregnancy test for&#xD;
             female pre-menopausal patients. NOTE: Women will be considered post-menopausal if they&#xD;
             have been amenorrheic for 12 months without an alternative medical cause. See section&#xD;
             5.4 for age-specific requirements (&lt;50 year old vs. ≥50 year old).&#xD;
&#xD;
          -  Females of childbearing potential randomized to Arm A and males randomized to Arm A or&#xD;
             Arm B must be willing to abstain from heterosexual activity or agree to use a highly&#xD;
             effective method of contraception from the time of informed consent until 90 days&#xD;
             after treatment discontinuation. Females of childbearing potential randomized to Arm B&#xD;
             must be willing to abstain from heterosexual activity or agree to use a highly&#xD;
             effective method of contraception until 180 days after treatment discontinuation. See&#xD;
             section 5.4 for definition of childbearing potential.&#xD;
&#xD;
          -  As determined by the enrolling physician or protocol designee, ability of the subject&#xD;
             to understand and comply with study procedures for the entire length of the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Patient must not have received any prior systemic therapy for stage IV NSCLC. Patients&#xD;
             must not have received prior anti-PD-1 or anti-PD-L1.&#xD;
&#xD;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings, and TB testing in line with&#xD;
             local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),&#xD;
             hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients&#xD;
             with a past or resolved HBV infection (defined as the presence of hepatitis B core&#xD;
             antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for&#xD;
             hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative&#xD;
             for HCV RNA. Testing is not required at screening.&#xD;
&#xD;
          -  Patients with history of non-infectious pneumonitis that required steroids or has&#xD;
             current pneumonitis. Has known history of Interstitial Lung Disease (ILD) or radiation&#xD;
             pneumonitis which required therapy with steroids.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory (including inflammatory bowel&#xD;
             disease [eg, colitis or Crohn's disease], diverticulitis, systemic lupus&#xD;
             erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with&#xD;
             polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]) and&#xD;
             pneumonitis. The following are exceptions to this criterion:&#xD;
&#xD;
               -  Diverticulosis&#xD;
&#xD;
               -  Patients with vitiligo or alopecia&#xD;
&#xD;
               -  Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone&#xD;
                  replacement&#xD;
&#xD;
               -  Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               -  Patients without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study sponsor investigator.&#xD;
&#xD;
               -  Patients with celiac disease controlled by diet alone&#xD;
&#xD;
          -  History of allogenic progenitor/stem cell or organ transplantation.&#xD;
&#xD;
          -  History of immunodeficiency. Patient should not be on any immunosuppressive therapy or&#xD;
             steroids &gt; prednisone 10mg/day or its equivalent on the day of the start of therapy.&#xD;
&#xD;
          -  Patients with current or prior use of immune suppressive therapy within 7 days of&#xD;
             starting study therapy. Following exceptions are allowed&#xD;
&#xD;
               -  Intranasal, local (eg. Intraarticular injections), inhaled or topical steroids&#xD;
&#xD;
               -  Steroids to prevent hypersensitivity reactions, eg. IV contrast for CT scans&#xD;
&#xD;
               -  Systemic steroids not to exceed 10mg of prednisone or its equivalent.&#xD;
&#xD;
          -  Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy&#xD;
             for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related&#xD;
             conditions (e.g., hormone replacement therapy) is acceptable.&#xD;
&#xD;
          -  Patients who have received live attenuated vaccine within 30 days of the first dose of&#xD;
             study therapy. Patients should not receive live vaccines while on therapy and for 30&#xD;
             days after the last dose.&#xD;
&#xD;
          -  Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the&#xD;
             mother is being treated on study).&#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. Patients&#xD;
                  with elevated PSA (prostate specific antigen) as the only evidence of prostate&#xD;
                  cancer may be considered for enrolment after discussion with the&#xD;
                  sponsor-investigator.&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  Patients with leptomeningeal carcinomatosis are not eligible. Patients with&#xD;
             symptomatic brain metastases are eligible only after receiving appropriate therapy,&#xD;
             are clinically stable and do not require steroids equivalent to 10 mg of prednisone&#xD;
             daily. Patients with asymptomatic brain metastases are eligible if the treating&#xD;
             physician determines that the brain metastases do not require immediate directed&#xD;
             therapy, they are clinically stable, and are not using steroids equivalent to &gt;10mg of&#xD;
             prednisone day prior to trial treatment.&#xD;
&#xD;
          -  Any unresolved toxicity from previous anticancer therapy Grade ≥2 except for alopecia,&#xD;
             vitiligo, and the laboratory values defined in the inclusion criteria.&#xD;
&#xD;
               -  Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis&#xD;
                  after consultation with the sponsor-investigator.&#xD;
&#xD;
               -  Patients with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
                  treatment with durvalumab may be included only after consultation with the&#xD;
                  sponsor-investigator.&#xD;
&#xD;
          -  Patients who have radiation therapy within 1 week prior to Day 1. Patients should have&#xD;
             recovered from any adverse events related to radiation therapy to ≤ grade 1 or&#xD;
             baseline. Patients must be considered stable to receive study therapy.&#xD;
&#xD;
          -  Participation in another clinical study with an investigational product within 30 days&#xD;
             prior to study registration.&#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;
          -  Major surgery as determined by the treating physician within 4 weeks of study&#xD;
             registration. Placement of a central access device (port) is not considered major&#xD;
             surgery.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness as determined by the treating physician, including&#xD;
             but not limited to, symptomatic congestive heart failure, uncontrolled hypertension,&#xD;
             unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious&#xD;
             chronic gastrointestinal conditions associated with diarrhea, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirement,&#xD;
             substantially increase risk of incurring AEs or compromise the ability of the patient&#xD;
             to give written informed consent.&#xD;
&#xD;
          -  History or hypersensitivity reaction to carboplatin, cisplatin or other&#xD;
             platinum-containing compounds, pemetrexed, or durvalumab.&#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>Shirish M Gadgeel, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Henry Ford Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hoosier Cancer Research Network</investigator_affiliation>
    <investigator_full_name>Shirish M Gadgeel</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Durvalumab</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/NCT04470674
org study id: HCRN LUN17-126
nct id: NCT04470674
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a two arm, randomized, phase II study of patients with advanced KRAS mutation
      positive and PD-L1 high NSCLC who have not received therapy for advanced stage disease.
      Patients will be randomized between Arm A and Arm B treatment. Arm A treatment will consist
      of durvalumab every 4 weeks for 13 cycles. Arm B treatment will consist of durvalumab with
      chemotherapy every 3 weeks for 4 cycles followed by durvalumab with pemetrexed every 3 weeks
      for 13 cycles.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: 12 months
description: Assess response rate by RECIST criteria 1.1 in Arm A and Arm B in advanced Kras mutation positive and PD-L1 high (≥50%) NSCLC patients.The objective response rate is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence
measure: Progression Free Survival
time frame: 12 months
description: A measurement from the date of randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs.
measure: Assess adverse events
time frame: 12 months
description: Adverse events will be summarized by frequency and severity using CTCAE version 5.
measure: Overall Survival
time frame: 12 months
description: Overall survival is defined by the date of randomization to date of death from any cause.
arm group label: Arm A (Durvalumab)
arm group type: Active Comparator
description: Durvalumab 1500 mg IV every 4 weeks for 13 cycles.
arm group label: Arm B (Durvalumab plus chemotherapy)
arm group type: Experimental
description: Durvalumab 1500 mg IV plus carboplatin AUC 5 IV and pemetrexed 500 mg/m2 IV every 3 weeks for 4 cycles followed by durvalumab and pemetrexed every 3 weeks for 13 more cycles.
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab 1500 mg
arm group label: Arm A (Durvalumab)
arm group label: Arm B (Durvalumab plus chemotherapy)
other name: IMFINZI
intervention type: Drug
intervention name: Carboplatin
description: carboplatin AUC 5
arm group label: Arm B (Durvalumab plus chemotherapy)
intervention type: Drug
intervention name: Pemetrexed
description: pemetrexed 500 mg/m2
arm group label: Arm B (Durvalumab plus chemotherapy)
other name: Alimta
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shirish M Gadgeel, MBBS
role: Principal Investigator
affiliation: Henry Ford Health System
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Hoosier Cancer Research Network
investigator full name: Shirish M Gadgeel
investigator title: Sponsor-Investigator
mesh term: Lung Neoplasms
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Durvalumab
sharing ipd: No