<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/NCT03293680</url>
  </required_header>
  <id_info>
    <org_study_id>GECP 16/06_PEBEL</org_study_id>
    <nct_id>NCT03293680</nct_id>
  </id_info>
  <brief_title>Pembrolizumab in Elderly Patients With Advanced Lung Cancer</brief_title>
  <official_title>Survival, Quality of Life and Self-reported Outcomes of Elderly Patients With Advanced Non-small Cell Lung Cancer Treated With Pembrolizumab (MK-3475) in the First Line Setting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spanish Lung Cancer Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spanish Lung Cancer Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center phase II trial of intravenous (IV) Pembrolizumab MK-3475 in subjects&#xD;
      older than 70 years with advanced Non-small cell Lung Cancer (NSCLC) expressing Programmed&#xD;
      death-ligand 1 (PD-L1). 82 patients will be enrolled in this trial to examine the efficacy,&#xD;
      the impact on geriatric assessments, the quality of life and the self-reported outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will receive MK-3475 at a fixed dose of 200 mg every 3 weeks (Q3W) (Figure 1).&#xD;
      Subjects will be evaluated every 9 weeks (63 ± 7 days) with radiographic imaging to assess&#xD;
      response to treatment. QoL and Self-reported Health Questionnaires, as well as geriatric&#xD;
      follow-up will be performed at the same intervals. Investigators will make all&#xD;
      treatment-based decisions using immune-related Response Criteria (irRC). However, for&#xD;
      determination of overall response rate (ORR) and progression-free survival (PFS), the&#xD;
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used. Adverse events will&#xD;
      be monitored throughout the trial and graded in severity according to the guidelines outlined&#xD;
      in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment with&#xD;
      MK-3475 will continue until two years of therapy have been administered, documented disease&#xD;
      progression, unacceptable adverse event(s), intercurrent illness that prevents further&#xD;
      administration of treatment, investigator's decision to withdraw the subject, subject&#xD;
      withdraws consent, noncompliance with trial treatment or procedure requirements, or&#xD;
      administrative reasons.&#xD;
&#xD;
      After the end of treatment, each subject will be followed for a minimum of 30 days for&#xD;
      adverse event monitoring (serious adverse events will be collected for up to 90 days after&#xD;
      the end of treatment unless the subject starts a new anticancer therapy between days 31 and&#xD;
      90). Subjects will have post-treatment follow-up for disease status, including initiating a&#xD;
      non-study cancer treatment and experiencing disease progression, until death, withdrawing&#xD;
      consent, or becoming lost to follow-up.&#xD;
&#xD;
      Participation in this trial will be dependent upon supplying tumor tissue from a newly&#xD;
      obtained formalin-fixed specimen from locations not radiated prior to biopsy. The specimen&#xD;
      will be evaluated at a central laboratory facility for expression status of Programmed&#xD;
      death-ligand 1(PD-L1) in a prospective manner. Only subjects whose tumors express Programmed&#xD;
      death-ligand 1(PD-L1) as determined by the central laboratory facility will be eligible for&#xD;
      inclusion in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 15, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 31, 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>Efficacy of the treatment at 12 months (overall survival of the patients)</measure>
    <time_frame>From the date of inclusion of the first patient to 12 months after this date</time_frame>
    <description>To evaluate the overall survival of the patients included at one year</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in health-related quality of life with Lung Cancer Symptom Scale</measure>
    <time_frame>From the first dose until 12 months (time of the last dose of treatment)</time_frame>
    <description>To evaluate changes in health-related quality of life in responder and non-responder patients older than 70 years with advanced non-small cell lung cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact on cognitive assessments measured with Edmonton scale</measure>
    <time_frame>From the first dose until the last dose of treatment (12 months later)</time_frame>
    <description>To evaluate the impact on cognitive geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact on functional assessments measured with Barthel scale</measure>
    <time_frame>From the first dose until the last dose of treatment (12 months later)</time_frame>
    <description>To evaluate the impact on functional geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From the inclusion date in the study until first progression (at 9 months approximately) documented according to RECIST criteria</time_frame>
    <description>To describe Progression-free Survival (PFS), according to RECIST criteria v. 1.1 of the first-line treatment with pembrolizumab (MK-3475) in elderly patients with advanced NSCLC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival rate at 2 years.</measure>
    <time_frame>From the date of inclusion of the first patient to 24 months after this date</time_frame>
    <description>To evaluate the overall survival of the patients included at two years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety (Adverse events) and tolerability (quantity of infusion and adverse events related with them) profile</measure>
    <time_frame>From the date of the first infusion of medication until 90 days after the last dose</time_frame>
    <description>To describe the safety and tolerability profile of first-line pembrolizumab (MK-3475) in previously untreated elderly patients</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 group, Pembrolizumab (MK-3475) 200 mg, every 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab (MK-3475) 200 mg, every 3 weeks</description>
    <arm_group_label>Pembrolizumab Arm</arm_group_label>
    <other_name>KEYTRUDA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histological or cytological documented stage III B or IV squamous and&#xD;
             non-squamous non-small-cell lung cancer previously untreated.&#xD;
&#xD;
          2. Epidermal Growth Factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) have to&#xD;
             be wild-type.&#xD;
&#xD;
          3. The subject must be willing and able to provide written informed consent/assent for&#xD;
             the trial.&#xD;
&#xD;
          4. Patients must be aged more than 70 years, on day of signing informed consent.&#xD;
&#xD;
          5. Measurable disease (at least 1 lesion) based on RECIST criteria v1.1. Patients will&#xD;
             not be eligible if this lesion was irradiated before inclusion.&#xD;
&#xD;
          6. Be willing to provide tissue from a newly obtained core or excision biopsy of a tumor&#xD;
             lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior&#xD;
             to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot&#xD;
             be provided (e.g. inaccessible or subject safety concern) may submit an archived&#xD;
             specimen only upon agreement from the Sponsor.&#xD;
&#xD;
          7. PD-L1 expression ≥ 1%&#xD;
&#xD;
          8. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group&#xD;
             Performance Scale.&#xD;
&#xD;
          9. Screening laboratory values must meet the following criteria (Table 1, see protocol),&#xD;
             all screening laboratory tests should be performed within 8 days of treatment&#xD;
             initiation.&#xD;
&#xD;
         10. Male subjects of childbearing potential must agree to use an adequate method of&#xD;
             contraception, starting with the first dose of study therapy through 120 days after&#xD;
             the last dose of study therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. 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.&#xD;
&#xD;
          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose&#xD;
             over 10 mg of prednisone or equivalent, or any other form of immunosuppressive therapy&#xD;
             within 7 days prior to the first dose of trial treatment.&#xD;
&#xD;
          3. Has a known history of active Tuberculosis Bacillus&#xD;
&#xD;
          4. Hypersensitivity to Pembrolizumab or any of its excipients.&#xD;
&#xD;
          5. Has had any prior anti-cancer therapy for his or her metastatic NSCLC. In the case of&#xD;
             patients who have progressed to a metastatic stage after having been treated for early&#xD;
             stage NSCLC, chemotherapy or radiation therapy as part of this previous treatment is&#xD;
             allowed, provided they have been completed more than three months ago. Patients who&#xD;
             received adjuvant or neoadjuvant treatment or both for early stages will be eligible&#xD;
             for this trial. All adverse events related to these previous treatments must have&#xD;
             recovered (i.e., ≤ Grade 1 or at baseline).&#xD;
&#xD;
          6. Has had any previous malignancy (except non melanoma skin cancer, and cancer in situ&#xD;
             of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast), unless a complete&#xD;
             remission was achieved at least 2 years prior to study entry and no additional therapy&#xD;
             is required or anticipated to be required during the study period.&#xD;
&#xD;
          7. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate if they&#xD;
             are stable (without evidence of progression by imaging for at least four weeks prior&#xD;
             to the first dose of trial treatment and any neurologic symptoms have returned to&#xD;
             baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids at a dose over 10 mg of prednisone or equivalent, for at least 7 days prior&#xD;
             to trial treatment. This exception does not include carcinomatous meningitis which is&#xD;
             excluded regardless of clinical stability.&#xD;
&#xD;
          8. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (eg., thyroxin, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          9. Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
         10. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         11. 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;
         12. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         13. Has any geriatric exclusion criteria:&#xD;
&#xD;
               -  advanced dementia (GDS ranking &gt;6)&#xD;
&#xD;
               -  moderate or severe functional dependence (Barthel Index &lt; 35)&#xD;
&#xD;
               -  Life expectancy less than one year, due to co-morbidities other than lung cancer.&#xD;
&#xD;
         14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C&#xD;
             Virus RNA [qualitative] is detected).&#xD;
&#xD;
         16. Has received a live vaccine within 30 days of planned start of study therapy. Note:&#xD;
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and&#xD;
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live&#xD;
             attenuated vaccines, and are not allowed.&#xD;
&#xD;
         17. Evidence of interstitial lung disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Remei Blanco, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Terrassa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ICO-Hospitalet</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorci Sanitari de Terrassa</name>
      <address>
        <city>Terrassa</city>
        <state>Barcelona</state>
        <zip>08227</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Sta Lucia</name>
      <address>
        <city>Cartagena</city>
        <state>Murcia</state>
        <zip>30202</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Lluís Alcanyís</name>
      <address>
        <city>Xàtiva</city>
        <state>Valencia</state>
        <zip>46800</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Luz</name>
      <address>
        <city>Cuenca</city>
        <zip>16002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Lucus Agustí</name>
      <address>
        <city>Lugo</city>
        <zip>27003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Dr. Peset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.gecp.org</url>
    <description>Web page of the sponsor where users can find more information about Fundación GECP studies</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>June 22, 2023</last_update_submitted>
  <last_update_submitted_qc>June 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 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>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 6, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03293680
org study id: GECP 16/06_PEBEL
nct id: NCT03293680
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multi-center phase II trial of intravenous (IV) Pembrolizumab MK-3475 in subjects
      older than 70 years with advanced Non-small cell Lung Cancer (NSCLC) expressing Programmed
      death-ligand 1 (PD-L1). 82 patients will be enrolled in this trial to examine the efficacy,
      the impact on geriatric assessments, the quality of life and the self-reported outcomes.
Subjects will receive MK-3475 at a fixed dose of 200 mg every 3 weeks (Q3W) (Figure 1).
      Subjects will be evaluated every 9 weeks (63 ± 7 days) with radiographic imaging to assess
      response to treatment. QoL and Self-reported Health Questionnaires, as well as geriatric
      follow-up will be performed at the same intervals. Investigators will make all
      treatment-based decisions using immune-related Response Criteria (irRC). However, for
      determination of overall response rate (ORR) and progression-free survival (PFS), the
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used. Adverse events will
      be monitored throughout the trial and graded in severity according to the guidelines outlined
      in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment with
      MK-3475 will continue until two years of therapy have been administered, documented disease
      progression, unacceptable adverse event(s), intercurrent illness that prevents further
      administration of treatment, investigator's decision to withdraw the subject, subject
      withdraws consent, noncompliance with trial treatment or procedure requirements, or
      administrative reasons.

      After the end of treatment, each subject will be followed for a minimum of 30 days for
      adverse event monitoring (serious adverse events will be collected for up to 90 days after
      the end of treatment unless the subject starts a new anticancer therapy between days 31 and
      90). Subjects will have post-treatment follow-up for disease status, including initiating a
      non-study cancer treatment and experiencing disease progression, until death, withdrawing
      consent, or becoming lost to follow-up.

      Participation in this trial will be dependent upon supplying tumor tissue from a newly
      obtained formalin-fixed specimen from locations not radiated prior to biopsy. The specimen
      will be evaluated at a central laboratory facility for expression status of Programmed
      death-ligand 1(PD-L1) in a prospective manner. Only subjects whose tumors express Programmed
      death-ligand 1(PD-L1) as determined by the central laboratory facility will be eligible for
      inclusion in this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy of the treatment at 12 months (overall survival of the patients)
time frame: From the date of inclusion of the first patient to 12 months after this date
description: To evaluate the overall survival of the patients included at one year
measure: Changes in health-related quality of life with Lung Cancer Symptom Scale
time frame: From the first dose until 12 months (time of the last dose of treatment)
description: To evaluate changes in health-related quality of life in responder and non-responder patients older than 70 years with advanced non-small cell lung cancer
measure: Impact on cognitive assessments measured with Edmonton scale
time frame: From the first dose until the last dose of treatment (12 months later)
description: To evaluate the impact on cognitive geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.
measure: Impact on functional assessments measured with Barthel scale
time frame: From the first dose until the last dose of treatment (12 months later)
description: To evaluate the impact on functional geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.
measure: Progression-free Survival (PFS)
time frame: From the inclusion date in the study until first progression (at 9 months approximately) documented according to RECIST criteria
description: To describe Progression-free Survival (PFS), according to RECIST criteria v. 1.1 of the first-line treatment with pembrolizumab (MK-3475) in elderly patients with advanced NSCLC
measure: Median Overall Survival rate at 2 years.
time frame: From the date of inclusion of the first patient to 24 months after this date
description: To evaluate the overall survival of the patients included at two years
measure: Safety (Adverse events) and tolerability (quantity of infusion and adverse events related with them) profile
time frame: From the date of the first infusion of medication until 90 days after the last dose
description: To describe the safety and tolerability profile of first-line pembrolizumab (MK-3475) in previously untreated elderly patients
arm group label: Pembrolizumab Arm
arm group type: Experimental
description: 1 group, Pembrolizumab (MK-3475) 200 mg, every 3 weeks
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab (MK-3475) 200 mg, every 3 weeks
arm group label: Pembrolizumab Arm
other name: KEYTRUDA
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Remei Blanco, PhD
role: Principal Investigator
affiliation: Hospital de Terrassa
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
url: http://www.gecp.org
description: Web page of the sponsor where users can find more information about Fundación GECP studies
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Pembrolizumab
sharing ipd: No
submitted: September 6, 2023