<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/NCT03014648</url>
  </required_header>
  <id_info>
    <org_study_id>HCC 16-153</org_study_id>
    <nct_id>NCT03014648</nct_id>
  </id_info>
  <brief_title>Evaluating the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>A Phase II Clinical Trial Evaluating the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer (NSCLC) in Patients Previously Treated With PD-1-directed Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Liza Villaruz, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II clinical trial aimed at evaluating the efficacy of PD-L1 inhibition with&#xD;
      atezolizumab in advanced squamous and non-squamous NSCLC patients previously treated with&#xD;
      anti-PD-1 therapy with either nivolumab or pembrolizumab.&#xD;
&#xD;
      In order to account for the variability of response kinetics to PD-1 directed therapy,&#xD;
      patients will be enrolled in 3 parallel cohorts based on the best overall response to PD-1&#xD;
      directed therapy.&#xD;
&#xD;
        -  Cohort 1 (progressive disease)&#xD;
&#xD;
        -  Cohort 2 (stable disease with minimum 12 weeks of therapy)&#xD;
&#xD;
        -  Cohort 3 (partial to complete response followed by progressive disease)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atezolizumab will be given on day 1 of a 21-day cycle at 1200 mg IV. Radiographic assessments&#xD;
      for disease response will occur every 6 weeks while on treatment. Confirmatory scans should&#xD;
      be obtained ≥ 4 weeks following initial documentation of objective response or progressive&#xD;
      disease on atezolizumab therapy.&#xD;
&#xD;
      Atezolizumab will be given as long as the patient continues to experience clinical benefit in&#xD;
      the opinion of the investigator or until unacceptable toxicity, symptomatic deterioration&#xD;
      attributed to disease progression.&#xD;
&#xD;
      Patients will be followed for 12 months or until death as per standard of care after&#xD;
      discontinuation of Atezolizumab or until death, whichever occurs first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2017</start_date>
  <completion_date type="Actual">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>Best Overall Response (BOR)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Best response recorded is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per RECIST v1.1: Complete Response (CR) - Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to &lt;10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of time that a tumor continues to respond to treatment from first documentation of response until disease progression.Per RECISIt v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to &lt;10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of time during and after treatment that a patient lives with disease but without disease progression. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of time from start of treatment that patients are still alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events ≥ Grade 3</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Adverse events will be graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Adverse events of grade 3 or greater determined to be possibly, probably or definitely related to treatment, or that result in dose holds or reductions, will be collected and reported. Adverse events and serious adverse events will be tabulated in order of prevalence, with the highest grade reported by each patient. The number and percent of subjects reporting adverse events will be summarized by category</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PD-L1 Expression</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>PD-L1 protein expression will be measured as positive (present) or negative (absent) in tissue from a biopsy conducted after discontinuation of the prior therapy and before initiation of study drug.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Advanced Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Atezolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Atezolizumab will be given on day 1 of a 21-day cycle at 1200 mg IV over 60 (plus or minus 15) minutes for first infusion; can be decreased to 30 (plus or minus 10) minutes for subsequent cycles.&#xD;
Atezolizumab will be given as long as the patient continues to experience clinical benefit in the opinion of the investigator or until unacceptable toxicity, symptomatic deterioration attributed to disease progression.&#xD;
There will be no dose reduction for Atezolizumab. Patients may temporarily suspend study treatment for up to 84 days beyond the scheduled date of delayed infusion if study drug-related toxicity requiring dose suspension is experienced. If Atezolizumab is held because of adverse events for greater than 84 days beyond the scheduled date of infusion, the patient will be discontinued from Atezolizumab and will be followed for safety and efficacy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab will be administered through an IV over 60 minutes at a dose of 1200mg on Day 1 of each 21-day cycle. If the first dose is tolerated without any infusion-related adverse events, the following doses can be administered over 30 minutes.</description>
    <arm_group_label>Atezolizumab</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Stage IIIB/IV squamous or non-squamous NSCLC (American Joint Committee&#xD;
             on Cancer 7th Edition Staging) who have had prior treatment with nivolumab or&#xD;
             pembrolizumab will be enrolled in one of 3 parallel cohorts based on the following:&#xD;
&#xD;
               -  Cohort 1: Patient with progressive disease on nivolumab or pembrolizumab as the&#xD;
                  best overall response. Progressive disease must be confirmed with a confirmatory&#xD;
                  scan ≤ 4 weeks after the 1st documented date of progression.&#xD;
&#xD;
               -  Cohort 2: Patients with stable disease as the best overall response on a minimum&#xD;
                  of 12 weeks of therapy with nivolumab or pembrolizumab.&#xD;
&#xD;
               -  Cohort 3: Patients with partial or complete response as the best overall response&#xD;
                  followed by progressive disease, on nivolumab or pembrolizumab. A confirmatory&#xD;
                  scan at the time of disease progression must be performed ≤ 4 weeks after the 1st&#xD;
                  documented date of progression.&#xD;
&#xD;
          -  Both men and women of all races and ethnic groups are eligible for this trial&#xD;
&#xD;
          -  Patients must have resolution of toxic effects to Grade 1 or less from prior therapy&#xD;
             (except alopecia).&#xD;
&#xD;
          -  Patients must sign Informed Consent Form and show ability and willingness to comply&#xD;
             with the requirements of the study protocol.&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  Willingness to undergo a biopsy ≤ 6 weeks of the start of study treatment to obtain&#xD;
             formalin-fixed paraffin-embedded tumor specimens in paraffin blocks (blocks are&#xD;
             preferred) or at least 15 unstained slides, with an associated pathology report, for&#xD;
             central testing of tumor PD-L1 expression.&#xD;
&#xD;
          -  Adequate hematologic and end organ function, defined by the following laboratory&#xD;
             results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):&#xD;
&#xD;
               -  ANC equal to/greater than 1500 cells/µL&#xD;
&#xD;
               -  WBC counts greater than 2500/µL&#xD;
&#xD;
               -  Lymphocyte count equal to/greater than 300µ/L&#xD;
&#xD;
               -  Platelet count equal to/greater than 100,000/µL&#xD;
&#xD;
               -  Hemoglobin equal to/greater than 9.0 g/dL&#xD;
&#xD;
               -  Total bilirubin equal to/less than 1.5 x ULN with the following exception:&#xD;
&#xD;
                    -  Patients with known Gilbert disease who have serum bilirubin level equal&#xD;
                       to/less than 3 x ULN may be enrolled.&#xD;
&#xD;
               -  AST and ALT equal to/less than 3.0 x ULN with the following exception:&#xD;
&#xD;
                    -  Patients with liver involvement: AST and/or ALT equal to/less than 5 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase equal to/less than 2.5 x ULN with the following exception:&#xD;
&#xD;
                    -  Patients with documented liver involvement or bone metastases: alkaline&#xD;
                       phosphatase equal to/less than 5 x ULN&#xD;
&#xD;
          -  Serum creatinine equal to/less than 1.5 x ULN or creatinine clearance equal to/greater&#xD;
             than 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate&#xD;
             estimation.&#xD;
&#xD;
          -  Measurable disease per RECIST v1.1 for patients with solid malignancies.&#xD;
&#xD;
          -  For female patients of childbearing potential and male patients with partners of&#xD;
             childbearing potential, agreement (by patient and/or partner) to use highly effective&#xD;
             form(s) of contraception (i.e., one that results in a low failure rate [less than 1%&#xD;
             per year] when used consistently and correctly) and to continue its use for 5 months&#xD;
             after the last dose of Atezolizumab.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1. Patients with an ECOG&#xD;
             Performance Status of 2 will be allowed at the discretion of the Treating Investigator&#xD;
             in agreement with the Sponsor-Investigator.&#xD;
&#xD;
          -  INR and aPTT equal to/less than 1.5 x ULN. This applies only to patients who do not&#xD;
             receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation&#xD;
             (such as low-molecular-weight heparin or warfarin) should be on a stable dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any approved anticancer therapy, including chemotherapy, hormonal therapy, or&#xD;
             radiotherapy, within 3 weeks prior to initiation of study treatment; however, the&#xD;
             following are allowed:&#xD;
&#xD;
               -  Hormone-replacement therapy or oral contraceptives.&#xD;
&#xD;
               -  Herbal therapy greater than 1 week prior to Cycle 1, Day 1 (herbal therapy&#xD;
                  intended as anticancer therapy must be discontinued at least 1 week prior to&#xD;
                  Cycle 1, Day 1).&#xD;
&#xD;
               -  Hormonal therapy for prostate cancer or breast cancer provided criteria in 3.2.21&#xD;
                  are met.&#xD;
&#xD;
                    -  Palliative radiotherapy (e.g., treatment of known bony metastases) allowed,&#xD;
                       provided it does not interfere with the assessment of tumor target lesions&#xD;
                       (e.g. the lesion being irradiated is not the only site of disease, because&#xD;
                       that would render the patient not evaluable for response by tumor&#xD;
                       assessments according to RECIST v1.1).&#xD;
&#xD;
          -  Adverse events from prior anticancer therapy that have not resolved to Grade equal&#xD;
             to/less than1 except for alopecia.&#xD;
&#xD;
          -  History of grade 4 immune-related adverse events requiring treatment with prednisone&#xD;
             or history of grade 3 immune-related adverse events requiring prednisone &gt;10 mg/kg for&#xD;
             &gt;12 weeks.&#xD;
&#xD;
          -  Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy&#xD;
             for other reasons (e.g., bone metastasis or osteoporosis) is allowed).&#xD;
&#xD;
          -  Known clinically significant liver disease, including active viral, alcoholic, or&#xD;
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease.&#xD;
&#xD;
          -  Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia,&#xD;
             chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory&#xD;
             myeloma.&#xD;
&#xD;
          -  Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases.&#xD;
             Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the&#xD;
             following criteria are met:&#xD;
&#xD;
               -  Evaluable or measurable disease outside the CNS.&#xD;
&#xD;
               -  No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm&#xD;
                  of the optic apparatus (optic nerves and chiasm).&#xD;
&#xD;
               -  No history of intracranial hemorrhage or spinal cord hemorrhage.&#xD;
&#xD;
               -  No ongoing requirement for dexamethasone for CNS disease; patients on a stable&#xD;
                  dose of anticonvulsants are permitted.&#xD;
&#xD;
               -  No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day&#xD;
                  1.&#xD;
&#xD;
          -  Patients with asymptomatic treated CNS metastases may be enrolled, provided all the&#xD;
             criteria listed above are met as well as the following:&#xD;
&#xD;
               -  Radiographic demonstration of improvement upon the completion of CNS directed&#xD;
                  therapy and no evidence of interim progression between the completion of&#xD;
                  CNS-directed therapy and the screening radiographic study.&#xD;
&#xD;
               -  No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle&#xD;
                  1, Day 1.&#xD;
&#xD;
               -  Screening CNS radiographic study equal to/greater than 4 weeks from completion of&#xD;
                  radiotherapy and equal to/greater than 2 weeks from discontinuation of&#xD;
                  corticosteroids.&#xD;
&#xD;
          -  Patients who are pregnant, are lactation, or breastfeeding.&#xD;
&#xD;
          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant&#xD;
             human antibodies.&#xD;
&#xD;
          -  Inability to comply with study and follow-up procedures.&#xD;
&#xD;
          -  History or risk of autoimmune disease, including but not limited to systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis&#xD;
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's&#xD;
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune&#xD;
             thyroid disease, vasculitis, or glomerulonephritis.&#xD;
&#xD;
               -  Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid&#xD;
                  replacement hormone may be eligible.&#xD;
&#xD;
               -  Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may&#xD;
                  be eligible.&#xD;
&#xD;
               -  Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with&#xD;
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis would&#xD;
                  be excluded) are permitted provided that they meet the following conditions:&#xD;
&#xD;
               -  Patients with psoriasis must have a baseline ophthalmologic exam to rule out&#xD;
                  ocular manifestations.&#xD;
&#xD;
               -  Rash must cover less than 10% of body surface area (BSA).&#xD;
&#xD;
               -  Disease is well controlled at baseline and only requiring low potency topical&#xD;
                  steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone&#xD;
                  0.01%, desonide 0.05%, alclometasone dipropionate 0.05%).&#xD;
&#xD;
               -  No acute exacerbations of underlying condition within the last 12 months (not&#xD;
                  requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids,&#xD;
                  biologic agents, oral calcineurin inhibitors; high potency or oral steroids).&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),&#xD;
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing&#xD;
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed&#xD;
             tomography (CT) scan. History of radiation pneumonitis in the radiation field&#xD;
             (fibrosis) is permitted.&#xD;
&#xD;
          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical&#xD;
             laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug or that may affect the&#xD;
             interpretation of the results or render the patient at high risk from treatment&#xD;
             complications.&#xD;
&#xD;
          -  History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C&#xD;
             infection.&#xD;
&#xD;
               -  Patients with past or resolved hepatitis B infection (defined as having a&#xD;
                  negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc&#xD;
                  [antibody to hepatitis B core antigen] antibody test) are eligible.&#xD;
&#xD;
               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction (PCR) is negative for HCV RNA.&#xD;
&#xD;
          -  Active tuberculosis.&#xD;
&#xD;
          -  Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to&#xD;
             hospitalization for complications of infection, bacteremia, or severe pneumonia.&#xD;
&#xD;
          -  Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.&#xD;
&#xD;
          -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. Patients&#xD;
             receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection&#xD;
             or chronic obstructive pulmonary disease) are eligible.&#xD;
&#xD;
          -  Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of&#xD;
             need for a major surgical procedure during the course of the study.&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 4 weeks before enrollment or&#xD;
             anticipation that such a live attenuated vaccine will be required during the study or&#xD;
             for 5 months after the last dose of Atezolizumab. Influenza vaccination should be&#xD;
             given during influenza season only (approximately October to March). Patients must not&#xD;
             receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to&#xD;
             enrollment, at any time during the study, or for 5 months after the last dose of&#xD;
             Atezolizumab.&#xD;
&#xD;
          -  Malignancies other than the disease under study within 5 years prior to Cycle 1, Day&#xD;
             1, with the exception of those with a negligible risk of metastasis or death and with&#xD;
             expected curative outcome (such as adequately treated carcinoma in situ of the cervix,&#xD;
             basal or squamous cell skin cancer, localized prostate cancer treated surgically with&#xD;
             curative intent, or ductal carcinoma in situ treated surgically with curative intent)&#xD;
             or undergoing active surveillance per standard-of-care management (e.g., chronic&#xD;
             lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score equal to/less&#xD;
             than 6, and prostate-specific antigen equal to/less than10 mg/mL, etc.).&#xD;
&#xD;
          -  Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within&#xD;
             five half lives of the investigational product, whichever is longer).&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications (including but not limited to&#xD;
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor&#xD;
             necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.&#xD;
&#xD;
               -  Patients who have received acute, low dose, systemic immunosuppressant&#xD;
                  medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.&#xD;
&#xD;
               -  The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)&#xD;
                  for patients with orthostatic hypotension or adrenocortical insufficiency is&#xD;
                  allowed.&#xD;
&#xD;
          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies or fusion proteins.&#xD;
&#xD;
          -  Patients with prior allogeneic bone marrow transplantation or prior solid organ&#xD;
             transplantation.&#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>Liza Villaruz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AdventHealth Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>April 10, 2022</last_update_submitted>
  <last_update_submitted_qc>April 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Liza Villaruz, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </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>Atezolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>December 29, 2022</submitted>
    <returned>January 23, 2023</returned>
    <submitted>February 17, 2023</submitted>
    <returned>March 15, 2023</returned>
    <submitted>March 27, 2023</submitted>
    <returned>April 17, 2023</returned>
    <submitted>April 18, 2023</submitted>
    <returned>May 10, 2023</returned>
  </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/NCT03014648
org study id: HCC 16-153
nct id: NCT03014648
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II clinical trial aimed at evaluating the efficacy of PD-L1 inhibition with
      atezolizumab in advanced squamous and non-squamous NSCLC patients previously treated with
      anti-PD-1 therapy with either nivolumab or pembrolizumab.

      In order to account for the variability of response kinetics to PD-1 directed therapy,
      patients will be enrolled in 3 parallel cohorts based on the best overall response to PD-1
      directed therapy.

        -  Cohort 1 (progressive disease)

        -  Cohort 2 (stable disease with minimum 12 weeks of therapy)

        -  Cohort 3 (partial to complete response followed by progressive disease)
Atezolizumab will be given on day 1 of a 21-day cycle at 1200 mg IV. Radiographic assessments
      for disease response will occur every 6 weeks while on treatment. Confirmatory scans should
      be obtained ≥ 4 weeks following initial documentation of objective response or progressive
      disease on atezolizumab therapy.

      Atezolizumab will be given as long as the patient continues to experience clinical benefit in
      the opinion of the investigator or until unacceptable toxicity, symptomatic deterioration
      attributed to disease progression.

      Patients will be followed for 12 months or until death as per standard of care after
      discontinuation of Atezolizumab or until death, whichever occurs first.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response (BOR)
time frame: Up to 6 years
description: Best response recorded is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per RECIST v1.1: Complete Response (CR) - Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Duration of Response (DOR)
time frame: Up to 6 years
description: The length of time that a tumor continues to respond to treatment from first documentation of response until disease progression.Per RECISIt v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
measure: Progression-free survival (PFS)
time frame: Up to 6 years
description: The length of time during and after treatment that a patient lives with disease but without disease progression. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
measure: Overall survival (OS)
time frame: Up to 6 years
description: The length of time from start of treatment that patients are still alive.
measure: Adverse Events ≥ Grade 3
time frame: Up to 6 years
description: Adverse events will be graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Adverse events of grade 3 or greater determined to be possibly, probably or definitely related to treatment, or that result in dose holds or reductions, will be collected and reported. Adverse events and serious adverse events will be tabulated in order of prevalence, with the highest grade reported by each patient. The number and percent of subjects reporting adverse events will be summarized by category
measure: PD-L1 Expression
time frame: Up to 6 years
description: PD-L1 protein expression will be measured as positive (present) or negative (absent) in tissue from a biopsy conducted after discontinuation of the prior therapy and before initiation of study drug.
arm group label: Atezolizumab
arm group type: Experimental
description: Atezolizumab will be given on day 1 of a 21-day cycle at 1200 mg IV over 60 (plus or minus 15) minutes for first infusion; can be decreased to 30 (plus or minus 10) minutes for subsequent cycles.
Atezolizumab will be given as long as the patient continues to experience clinical benefit in the opinion of the investigator or until unacceptable toxicity, symptomatic deterioration attributed to disease progression.
There will be no dose reduction for Atezolizumab. Patients may temporarily suspend study treatment for up to 84 days beyond the scheduled date of delayed infusion if study drug-related toxicity requiring dose suspension is experienced. If Atezolizumab is held because of adverse events for greater than 84 days beyond the scheduled date of infusion, the patient will be discontinued from Atezolizumab and will be followed for safety and efficacy.
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab will be administered through an IV over 60 minutes at a dose of 1200mg on Day 1 of each 21-day cycle. If the first dose is tolerated without any infusion-related adverse events, the following doses can be administered over 30 minutes.
arm group label: Atezolizumab
other name: Tecentriq
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Liza Villaruz, MD
role: Principal Investigator
affiliation: University of Pittsburgh Medical Center
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Liza Villaruz, MD
investigator title: Assistant Professor of Medicine
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Atezolizumab
sharing ipd: No
submitted: December 29, 2022
returned: January 23, 2023
submitted: February 17, 2023
returned: March 15, 2023
submitted: March 27, 2023
returned: April 17, 2023
submitted: April 18, 2023
returned: May 10, 2023