<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/NCT03242915</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2017.057</org_study_id>
    <secondary_id>HUM00129169</secondary_id>
    <nct_id>NCT03242915</nct_id>
  </id_info>
  <brief_title>Pembrolizumab in Combination With Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients With Targetable Genetic Alterations, Previously Treated With Appropriate Targeted Agents, With Progressive Disease</brief_title>
  <official_title>Phase II Multi-center Study of Pembrolizumab in Combination With Platinum-based Doublet Chemotherapy in NSCLC (Non-small Cell Lung Cancer) Patients With Targetable Genetic Alterations in Their Tumor Previously Treated With Appropriate Targeted Agents With Progressive Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigators hypothesize that addition of pembrolizumab will enhance the efficacy of&#xD;
      carboplatin and pemetrexed in patients with EGFR-mutation-positive NSCLC, or patients with&#xD;
      other genetic alterations, and who have disease progression following appropriate targeted&#xD;
      therapies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 3, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2</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>The number of patients that respond to treatment</measure>
    <time_frame>Until disease progression or until study stops (up to ~5 years)</time_frame>
    <description>The primary endpoint is Response Rate (RR) defined as the rate of complete and partial response. Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (&lt;10mm short axis). Partial Response (PR): Persistence of one or more non-target lesion(s) but does not qualify for PD. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) time</measure>
    <time_frame>Until disease progression or until study stops (up to ~5 years)</time_frame>
    <description>PFS is defined as the duration of time from registration to time of progression. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) time</measure>
    <time_frame>Until death or until study stops (up to ~5 years)</time_frame>
    <description>Overall survival is defined as the time from registration to time of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab/Carboplatin/Pemetrexed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200mg IV every 3 weeks</description>
    <arm_group_label>Pembrolizumab/Carboplatin/Pemetrexed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC 5 IV every 3 weeks</description>
    <arm_group_label>Pembrolizumab/Carboplatin/Pemetrexed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>500 mg/m^2 IV every 3 weeks</description>
    <arm_group_label>Pembrolizumab/Carboplatin/Pemetrexed</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cohort-specific:&#xD;
&#xD;
        Cohort 1- EGFR mutation positive NSCLC patients previously treated with appropriate&#xD;
        targeted therapy with progressive and measurable disease per RECIST 1.1 criteria tumor.&#xD;
&#xD;
        Cohort 2- Other genetically altered NSCLC patients previously treated with appropriate&#xD;
        targeted therapy with progressive and measurable tumor.&#xD;
&#xD;
          -  Tumor tissue for PD-L1 assessment should be available unless PD-L1 assessment results&#xD;
             are already available.&#xD;
&#xD;
          -  Patients should not have received any systemic chemotherapy for advanced NSCLC.&#xD;
             Patients who received 1 cycle of systemic chemotherapy for advanced NSCLC while&#xD;
             awaiting the results of tumor molecular analysis and subsequently were switched to&#xD;
             appropriate targeted therapy will be eligible. Patients who have received neoadjuvant,&#xD;
             adjuvant or as part of concurrent chemotherapy and radiation are eligible if they&#xD;
             received the chemotherapy 12 months or more before the start of study therapy.&#xD;
&#xD;
          -  ECOG PS 0-1 (Eastern Cooperative Oncology Group Performance Status: an attempt to&#xD;
             quantify cancer patients' general well-being and activities of daily life. The score&#xD;
             ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)&#xD;
&#xD;
          -  Patients should have recovered to ≤ grade 1 from clinically meaningful (example&#xD;
             alopecia is not considered clinically meaningful) adverse events related to prior&#xD;
             treatments.&#xD;
&#xD;
          -  Patients should be willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Demonstrate adequate organ function&#xD;
&#xD;
          -  Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 1 week of enrollment.&#xD;
&#xD;
          -  Female subjects of childbearing potential must be willing to use an adequate method of&#xD;
             contraception&#xD;
&#xD;
          -  Male subjects of child bearing potential must agree to use an adequate method of&#xD;
             contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  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 the first dose of treatment. If the half-life of the drug is&#xD;
             known then starting therapy 5 half-lives after the end of the last therapy is&#xD;
             acceptable.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency. Patient should not be of any immunosuppressive&#xD;
             therapy or steroids &gt; prednisone 10mg/day or its equivalent on the day of the start of&#xD;
             therapy.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis)&#xD;
&#xD;
          -  Hypersensitivity to pembrolizumab, carboplatin or pemetrexed or any of its excipients.&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events&#xD;
             due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Has had targeted small molecule therapy, or palliative radiation therapy within 1 week&#xD;
             prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from&#xD;
             adverse events due to a previously administered agent.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment or&#xD;
             the treating physician believes will require therapy within 1 year.&#xD;
&#xD;
          -  Has symptomatic central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
&#xD;
          -  Has known history of non-infectious pneumonitis that required steroids or has current&#xD;
             pneumonitis. Has known history of interstitial lung disease.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  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 subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active Hepatitis B or Hepatitis C&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy.&#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>Gregory Kalemkerian, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Cancer Institute/Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Cancer Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</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>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 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>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Pemetrexed</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/NCT03242915
org study id: UMCC 2017.057
secondary id: HUM00129169
nct id: NCT03242915
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Investigators hypothesize that addition of pembrolizumab will enhance the efficacy of
      carboplatin and pemetrexed in patients with EGFR-mutation-positive NSCLC, or patients with
      other genetic alterations, and who have disease progression following appropriate targeted
      therapies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The number of patients that respond to treatment
time frame: Until disease progression or until study stops (up to ~5 years)
description: The primary endpoint is Response Rate (RR) defined as the rate of complete and partial response. Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (<10mm short axis). Partial Response (PR): Persistence of one or more non-target lesion(s) but does not qualify for PD. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).
measure: Progression free survival (PFS) time
time frame: Until disease progression or until study stops (up to ~5 years)
description: PFS is defined as the duration of time from registration to time of progression. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).
measure: Overall survival (OS) time
time frame: Until death or until study stops (up to ~5 years)
description: Overall survival is defined as the time from registration to time of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive.
arm group label: Pembrolizumab/Carboplatin/Pemetrexed
arm group type: Experimental
description: Pembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks
intervention type: Drug
intervention name: Pembrolizumab
description: 200mg IV every 3 weeks
arm group label: Pembrolizumab/Carboplatin/Pemetrexed
intervention type: Drug
intervention name: Carboplatin
description: AUC 5 IV every 3 weeks
arm group label: Pembrolizumab/Carboplatin/Pemetrexed
intervention type: Drug
intervention name: Pemetrexed
description: 500 mg/m^2 IV every 3 weeks
arm group label: Pembrolizumab/Carboplatin/Pemetrexed
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Kalemkerian, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Disease Progression
mesh term: Carboplatin
mesh term: Pembrolizumab
mesh term: Pemetrexed