<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/NCT04487756</url>
  </required_header>
  <id_info>
    <org_study_id>IOR-IISML42037</org_study_id>
    <secondary_id>2020-000448-72</secondary_id>
    <nct_id>NCT04487756</nct_id>
  </id_info>
  <brief_title>Combination of Atezolizumab With Dendritic Cell Vaccine in Patients With Lung Cancer</brief_title>
  <acronym>VENEZO-LUNG</acronym>
  <official_title>Phase Ib/II Trial of the Combination of Atezolizumab With Dendritic Cell Vaccination as Maintenance Treatment in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) After Induction Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Oncológico Dr Rosell</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundacion Clinic per a la Recerca Biomédica</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto Oncológico Dr Rosell</source>
  <oversight_info>
    <has_dmc>Yes</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 single-arm Phase Ib/II multicenter open-label study, with translational sub-study,&#xD;
      of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in&#xD;
      extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites&#xD;
      will include patients in this study.&#xD;
&#xD;
      Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab&#xD;
      for four 21-day cycles (induction phase), followed by a maintenance phase during which they&#xD;
      will receive the dendritic cell vaccine (6 doses maximum) in combination with atezolizumab&#xD;
      until they had unacceptable toxic effects, disease progression according to Response&#xD;
      Evaluation Criteria in Solid Tumors (RECIST), version 1.1, or no additional clinical benefit.&#xD;
&#xD;
      The two primary endpoints are the investigator-assessed toxicity and the 6 months PFS, both&#xD;
      in the intention-to-treat population. Secondary Outcome Measures include: Duration of&#xD;
      clinical benefit (DCB), Overall survival (OS) and Overall response rate (ORR)&#xD;
&#xD;
      The translational substudy will include:&#xD;
&#xD;
      Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA&#xD;
      expression, Work Environmental Scale (WES) analysis, and flow cytometry in pretreatment fresh&#xD;
      tumor tissue.&#xD;
&#xD;
      The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA&#xD;
      analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study,&#xD;
      of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in&#xD;
      extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites&#xD;
      will include patients in this study.&#xD;
&#xD;
      Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab&#xD;
      for four 21-day cycles (induction phase), followed by a maintenance phase during which they&#xD;
      will receive atezolizumab and dendritic cell vaccine combination until they had unacceptable&#xD;
      toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors&#xD;
      (RECIST), version 1.1, or no additional clinical benefit. The two primary endpoints are the&#xD;
      investigator-assessed toxicity and the 6 months PFS, both in the intention-to-treat&#xD;
      population.&#xD;
&#xD;
      In the Phase Ib safety lead-in portion, up to 6 patients will be enrolled into and evaluated&#xD;
      for dose-limiting toxicities (DLT) during the first 2 cycles of the maintenance therapy. If&#xD;
      &lt;2 out of 6 patients present with limiting toxicities, the administration of the&#xD;
      investigational products will be deemed safe in the Phase 1b lead-in, therefore enrollment&#xD;
      will be expanded into the Phase 2 cohort. Inclusion and treatment of up to 20 patients&#xD;
      (including those enrolled in the Phase Ib lead-in) with atezolizumab and dendritic cell&#xD;
      vaccination as maintenance therapy is finally expected.&#xD;
&#xD;
      Safety assessments will be based on adverse event reports, results of clinical laboratory&#xD;
      tests, immune safety tests, physical examinations, vital sign measurements, Eastern&#xD;
      Cooperative Oncology Group (ECOG) performance status both during the study, and up to six&#xD;
      months following the last study drug administration. Adverse events (AEs) will be assessed&#xD;
      throughout the study period and evaluated by using National Cancer Institute (NCI) Common&#xD;
      Technology Criteria version of Adverse Events version 5.0 (NCI CTCAE v 5.0).&#xD;
&#xD;
      Tumor measurements will be performed by computed tomography (CT) scan at baseline, at week 6&#xD;
      (W6), at week 12 (W12), and every 9 weeks thereafter, to evaluate 6m PFS and response to&#xD;
      treatment. The response will be evaluated using the Response Evaluation Criteria in Solid&#xD;
      Tumors version 1.1 (RECIST 1.1) and the immune-related response criteria (irRECIST) as a&#xD;
      secondary endpoint. Brain magnetic resonance imaging (MRI) will be performed at baseline&#xD;
      (mandatory as per clinical practice), and along with CT scan at each timepoint, if there are&#xD;
      brain metastasis at baseline.&#xD;
&#xD;
      Patients with stable disease (SD), partial response (PR) or complete response (CR) after&#xD;
      induction with chemotherapy plus atezolizumab (CT scan on W12) will continue during the&#xD;
      maintenance phase with atezolizumab plus dendritic cell vaccine.&#xD;
&#xD;
      Treatment with atezolizumab will continue until disease progression (PD), significant&#xD;
      clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal from the&#xD;
      trial is fulfilled.&#xD;
&#xD;
      Treatment with dendritic cell vaccines will continue for a maximum of 6 doses until PD,&#xD;
      significant clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal&#xD;
      from the trial are fulfilled (whichever occurs first).&#xD;
&#xD;
      Treatment may continue after the initial determination of PD per RECIST 1.1 if the subject's&#xD;
      performance status remains stable, and if the opinion of the principal investigator, the&#xD;
      subject will benefit from continued treatment and if other criteria are fulfilled as outlined&#xD;
      in the protocol.&#xD;
&#xD;
      For patients who have a confirmed CR or PR, it should be considered prophylactic cranial&#xD;
      irradiation (PCI) after completion of chemotherapy (i.e., induction) based on the&#xD;
      investigator's judgment. Following the completion of the induction part, PCI may be&#xD;
      administered concurrently with atezolizumab and dendritic cell vaccination during the&#xD;
      maintenance part. For those patients who have not progressed at the time of study drug&#xD;
      discontinuation, the tumor assessments (including all disease locations) will be assessed&#xD;
      radiologically by CT or MRI, as performed at screening, every 9 weeks (approximately 63 ± 7&#xD;
      days), until the occurrence of PD or study completion. The same method of assessment (CT or&#xD;
      MRI) should be used to characterize tumors at screening and at all follow-up assessments. If&#xD;
      positron emission tomography (PET) is used, it should also be accompanied by spiral CT or&#xD;
      MRI.&#xD;
&#xD;
      Safety will be defined based on the rate of serious adverse events (SAEs) comparing with&#xD;
      historic controls of atezolizumab in monotherapy as a maintenance treatment.&#xD;
&#xD;
      Kaplan Meier method will be used to estimate the survival function. Translational study&#xD;
&#xD;
      Tumor samples: All patients will undergo baseline tumor tissue acquisition prior to&#xD;
      enrollment. The only mandatory tissue biopsy is pretreatment. Tissue samples:&#xD;
&#xD;
      Pre induction treatment fresh and paraffin-embedded tumor sample (If obtaining a fresh biopsy&#xD;
      is not feasible, the case should be discussed with Coordinating Investigators) Pre&#xD;
      maintenance phase (for those that rebiopsy is feasible) After 24 weeks on maintenance phase&#xD;
      (for those patents that continue on treatment after w24 on maintenance and rebiopsy is&#xD;
      feasible) At tumor progression (for those patients who progressed and rebiopsy is feasible).&#xD;
&#xD;
      Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA&#xD;
      expression, WES analysis, and flow cytometry in pretreatment fresh tumor tissue.&#xD;
&#xD;
      Peripheral blood samples: Peripheral blood samples will be collected:&#xD;
&#xD;
      Pre induction treatment Pre maintenance phase After 9 weeks of the first vaccination At&#xD;
      progression of the disease The analysis will consist of T cell immunophenotyping, DC&#xD;
      immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by&#xD;
      WES and cytokine analysis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 17, 2021</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 1/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>
    <intervention_model_description>single arm Phase Ib/II multicenter open label study, with translational sub-study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-Free Survival (PFS) rate at 6 months</measure>
    <time_frame>At 6 months after start of treatment</time_frame>
    <description>Calculated as the percentage of participants alive and without disease progression, as assessed by the Investigator using RECIST v1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency and severity of AEs and SAEs (Safety)</measure>
    <time_frame>Throughout the study. Approximately 3 years</time_frame>
    <description>he number of patients with AEs and SAEs, changes in laboratory values, vital signs, ECGs, and results of physician examinations graded according to the CTCAE v 5.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of clinical benefit (DCB) as per RECIST 1.1</measure>
    <time_frame>Throughout the study. Approximately 3 years</time_frame>
    <description>DCB calculated as the time (in months) from first dose of treatment to progression (or death from any cause) in patients who had a best overall response of CR, PR, or SD of ≥ 24 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Throughout the study. Approximately 3 years</time_frame>
    <description>Median Overall Survival (mOS) is calculated as the time from date of inclusion to date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR1) as per RECIST 1.1</measure>
    <time_frame>Throughout the study. Approximately 3 years</time_frame>
    <description>Rate of patients that achieve partial or complete response as best response during study induction treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR2) as per RECIST 1.1</measure>
    <time_frame>Throughout the study. Approximately 3 years</time_frame>
    <description>Rate of patients that have a further best response during maintenance treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Extensive-stage Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Atezo+DCvac</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- Induction (4 cycles, every 3 weeks): Carboplatin area under the curve (AUC) 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle) Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)&#xD;
- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks) DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab 1200 mg in 20 ML Injection</intervention_name>
    <description>- Induction (4 cycles, every 3 weeks): Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)&#xD;
- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks)</description>
    <arm_group_label>Atezo+DCvac</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ADC Vaccine</intervention_name>
    <description>- Maintenance (only patients without PD after 4 induction cycles, up to PD): DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.</description>
    <arm_group_label>Atezo+DCvac</arm_group_label>
    <other_name>Autologous Dendritic cell (ADC) vaccine, Dendritic cell (DC) vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>- Induction (4 cycles, every 3 weeks): Carboplatin AUC 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle)</description>
    <arm_group_label>Atezo+DCvac</arm_group_label>
    <other_name>Carboplatino (Teva/Accord/Pharmacia)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histological diagnosis of extensive-stage small cell lung cancer (ES-SCLC).&#xD;
             Unequivocally confirmed diagnosis of SCLC by histology preferably including the&#xD;
             presence of neuroendocrine features by immunohistochemistry.&#xD;
&#xD;
          2. Centrally confirmed tumor tissue viability for vaccine preparation.&#xD;
&#xD;
          3. No previous cancer treatment for advanced disease&#xD;
&#xD;
          4. Life expectancy at least 16 weeks&#xD;
&#xD;
          5. ECOG performance status 0 or 1.&#xD;
&#xD;
          6. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
             Absolute neutrophil count ≥ 1.5 x 109 cells/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9&#xD;
             g/dL Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 x upper limit of normal&#xD;
             (ULN) (≤ 5 x ULN, if documented liver metastases are present) Total bilirubin ≤ 2 x&#xD;
             ULN (except patients with documented Gilbert's syndrome) Creatinine &lt; 2 mg/dl (or a&#xD;
             glomerular filtration rate &gt; 60)&#xD;
&#xD;
          7. Prior palliative radiotherapy must have been completed at least 2 weeks prior to start&#xD;
             the study treatment (subjects may receive localized palliative radiotherapy while&#xD;
             receiving study drug).&#xD;
&#xD;
          8. Subjects with brain metastases are eligible if they are asymptomatic, are treated, or&#xD;
             are neurological stable for at least 2 weeks without the use of steroids, or on a&#xD;
             stable or decreasing dose of &lt; 10 mg daily prednisone or equivalent.&#xD;
&#xD;
          9. Must be willing and able to accept one leukapheresis procedures&#xD;
&#xD;
         10. Written informed consent of approved by the investigator's Institutional Review Board&#xD;
             (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial&#xD;
             activities.&#xD;
&#xD;
         11. Male or female subjects aged ≥ 18 years.&#xD;
&#xD;
         12. Measurable disease by RECIST.1.1 criteria.&#xD;
&#xD;
         13. Highly effective contraception for both male and female subjects throughout the study&#xD;
             and for at least 30 days after the last atezolizumab treatment administration if the&#xD;
             risk of conception exists.&#xD;
&#xD;
         14. Negative serum pregnancy test at screening for women of childbearing potential. Female&#xD;
             subjects must either be of non-reproductive potential (ie, post-menopausal by history:&#xD;
             ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR&#xD;
             history of hysterectomy, OR history of bilateral tubal ligation, OR history of&#xD;
             bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.&#xD;
&#xD;
         15. Central negative serologic determination to HBsAg, Anti-HBc, HBV, HCV, HCV RNA, HIV-I&#xD;
             RNA, Agp24 IIIV + AC IIIV ½ (MLIA) serum, IgG antigen core v. hepatitis B, RPR (Ac&#xD;
             reaginic Lues-RPR, serum), Ac anti-HTLV I/II (if the patient came from an endemic&#xD;
             zone), Ac anti-Trypanosoma Cruzi, Chagas, (if a patient came from the endemic zone),&#xD;
             when RPR positive or doubtful for confirmation: IgG T. pallidum (ELISA) immunoglobulin&#xD;
             M (IgM) T. pallidum (ELISA), when IgG T. Pallidum doubtful: Pt confirmatory&#xD;
             immunoglobulin G (IgG)/IGM, T pallidum (LIA).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior chemotherapy for extensive-stage ES-SCLC&#xD;
&#xD;
          2. Any prior anti-PD-1/PD-L1 antibody therapy&#xD;
&#xD;
          3. History of, or significant evidence of risk for, severe chronic inflammatory or&#xD;
             autoimmune disease&#xD;
&#xD;
          4. Potential requirement for systemic corticosteroids or concurrent immunosuppressive&#xD;
             drugs based on prior history or received systemic steroids within the last 2 weeks&#xD;
             prior to enrollment (inhaled or topical steroids at standard doses are allowed)&#xD;
&#xD;
          5. Human immunodeficiency virus (HIV) seropositivity, active Hepatitis B or C&#xD;
             seropositivity&#xD;
&#xD;
          6. Dementia or significantly altered mental status that would prohibit the understanding&#xD;
             or rendering of informed consent and compliance with the requirements of this protocol&#xD;
&#xD;
          7. Pregnancy or breastfeeding; female patients must be surgically sterile or be&#xD;
             postmenopausal for two years or must agree to use effective contraception during the&#xD;
             period of treatment and 6 months after; all female patients with reproductive&#xD;
             potential must have a negative pregnancy test (serum/urine) within 24 hours from&#xD;
             starting the conditioning chemotherapy; the definition of effective contraception will&#xD;
             be based on the judgment of the study investigators; patients who are breastfeeding&#xD;
             are not allowed on study&#xD;
&#xD;
          8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects&#xD;
             with irreversible toxicity that is not reasonably expected to be exacerbated by the&#xD;
             investigational product may be included (e.g., hearing loss, peripheral neuropathy).&#xD;
&#xD;
          9. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects&#xD;
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within&#xD;
             the past 2 years) are not excluded. For phase I cohort, patients with autoimmune&#xD;
             paraneoplastic syndromes will be also excluded.&#xD;
&#xD;
         10. Any syndrome that requires systemic corticosteroid/immunosuppressive medication EXCEPT&#xD;
             for syndromes which would not be expected to recur in the absence of an external&#xD;
             trigger (vitiligo, autoimmune thyroiditis, or type 1 diabetes mellitus are permitted&#xD;
             to enroll)&#xD;
&#xD;
         11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             ulcerative colitis).&#xD;
&#xD;
         12. History of primary immunodeficiency.&#xD;
&#xD;
         13. History of allogeneic organ transplant. 14 History of hypersensitivity to atezolizumab&#xD;
             / ADC vaccine or any excipient.&#xD;
&#xD;
        15- Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
        infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina&#xD;
        pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding&#xD;
        diathesis including any subject known to have evidence of acute or chronic hepatitis B or C&#xD;
        or psychiatric illness/social situations that would limit compliance with study&#xD;
        requirements or compromise the ability of the subject to give written informed consent.&#xD;
&#xD;
        16- Known history of active tuberculosis. 17- Subjects with previous malignancies (except&#xD;
        for non-melanoma skin cancer, and cancer in situ of the bladder, gastric, colon,&#xD;
        cervical/dysplasia, melanoma, breast) are excluded unless a complete remission was achieved&#xD;
        at least 5 years prior to study entry and no additional therapy is required or anticipated&#xD;
        to be required during the study period.&#xD;
&#xD;
        18- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30&#xD;
        days of receiving atezolizumab.&#xD;
&#xD;
        19- Prior allogeneic stem-cell transplantation. 20- Known severe hypersensitivity reactions&#xD;
        to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or&#xD;
        uncontrolled asthma.&#xD;
&#xD;
        21- Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
        reproductive potential who are not willing to employ highly effective birth control from&#xD;
        screening to 180 days after the last dose of ADC + atezolizumab combination 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>María González Cao</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Quirón-Dexeus</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>A responsible person designated by the sponsor</last_name>
    <phone>93 434 44 12</phone>
    <email>investigacion@mfar.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Responsible person designated by the sponsor</last_name>
    <phone>93 434 44 12</phone>
    <email>investigacion@mfar.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>ICO Badalona</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Principal Investigator Selected by Sponsor, M.D., Ph.D.</last_name>
      <email>investigacion@mfar.net</email>
    </contact>
    <investigator>
      <last_name>Principal Investigator Selected by Sponsor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Quirón Dexeus</name>
      <address>
        <city>Barcelona</city>
        <zip>08028</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Investigator Selected by Sponsor, M.D., Ph.D.</last_name>
      <email>investigacion@mfar.net</email>
    </contact>
    <investigator>
      <last_name>Principal investigator Selected by Sponsor, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Investigator Selected by Sponsor, M.D.</last_name>
      <email>investigacion@mfar.net</email>
    </contact>
    <investigator>
      <last_name>Principal investigator Selected by Sponsor, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>June 29, 2022</last_update_submitted>
  <last_update_submitted_qc>June 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Small cell lung cancer</keyword>
  <keyword>Atezolizumab</keyword>
  <keyword>Dendritic cell vaccine</keyword>
  <keyword>Safety</keyword>
  <keyword>Efficacy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Vaccines</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/NCT04487756
org study id: IOR-IISML42037
secondary id: 2020-000448-72
nct id: NCT04487756
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study,
      of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in
      extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites
      will include patients in this study.

      Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab
      for four 21-day cycles (induction phase), followed by a maintenance phase during which they
      will receive the dendritic cell vaccine (6 doses maximum) in combination with atezolizumab
      until they had unacceptable toxic effects, disease progression according to Response
      Evaluation Criteria in Solid Tumors (RECIST), version 1.1, or no additional clinical benefit.

      The two primary endpoints are the investigator-assessed toxicity and the 6 months PFS, both
      in the intention-to-treat population. Secondary Outcome Measures include: Duration of
      clinical benefit (DCB), Overall survival (OS) and Overall response rate (ORR)

      The translational substudy will include:

      Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA
      expression, Work Environmental Scale (WES) analysis, and flow cytometry in pretreatment fresh
      tumor tissue.

      The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA
      analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis
This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study,
      of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in
      extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites
      will include patients in this study.

      Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab
      for four 21-day cycles (induction phase), followed by a maintenance phase during which they
      will receive atezolizumab and dendritic cell vaccine combination until they had unacceptable
      toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors
      (RECIST), version 1.1, or no additional clinical benefit. The two primary endpoints are the
      investigator-assessed toxicity and the 6 months PFS, both in the intention-to-treat
      population.

      In the Phase Ib safety lead-in portion, up to 6 patients will be enrolled into and evaluated
      for dose-limiting toxicities (DLT) during the first 2 cycles of the maintenance therapy. If
      <2 out of 6 patients present with limiting toxicities, the administration of the
      investigational products will be deemed safe in the Phase 1b lead-in, therefore enrollment
      will be expanded into the Phase 2 cohort. Inclusion and treatment of up to 20 patients
      (including those enrolled in the Phase Ib lead-in) with atezolizumab and dendritic cell
      vaccination as maintenance therapy is finally expected.

      Safety assessments will be based on adverse event reports, results of clinical laboratory
      tests, immune safety tests, physical examinations, vital sign measurements, Eastern
      Cooperative Oncology Group (ECOG) performance status both during the study, and up to six
      months following the last study drug administration. Adverse events (AEs) will be assessed
      throughout the study period and evaluated by using National Cancer Institute (NCI) Common
      Technology Criteria version of Adverse Events version 5.0 (NCI CTCAE v 5.0).

      Tumor measurements will be performed by computed tomography (CT) scan at baseline, at week 6
      (W6), at week 12 (W12), and every 9 weeks thereafter, to evaluate 6m PFS and response to
      treatment. The response will be evaluated using the Response Evaluation Criteria in Solid
      Tumors version 1.1 (RECIST 1.1) and the immune-related response criteria (irRECIST) as a
      secondary endpoint. Brain magnetic resonance imaging (MRI) will be performed at baseline
      (mandatory as per clinical practice), and along with CT scan at each timepoint, if there are
      brain metastasis at baseline.

      Patients with stable disease (SD), partial response (PR) or complete response (CR) after
      induction with chemotherapy plus atezolizumab (CT scan on W12) will continue during the
      maintenance phase with atezolizumab plus dendritic cell vaccine.

      Treatment with atezolizumab will continue until disease progression (PD), significant
      clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal from the
      trial is fulfilled.

      Treatment with dendritic cell vaccines will continue for a maximum of 6 doses until PD,
      significant clinical deterioration, unacceptable toxicity, or if any criteria for withdrawal
      from the trial are fulfilled (whichever occurs first).

      Treatment may continue after the initial determination of PD per RECIST 1.1 if the subject's
      performance status remains stable, and if the opinion of the principal investigator, the
      subject will benefit from continued treatment and if other criteria are fulfilled as outlined
      in the protocol.

      For patients who have a confirmed CR or PR, it should be considered prophylactic cranial
      irradiation (PCI) after completion of chemotherapy (i.e., induction) based on the
      investigator's judgment. Following the completion of the induction part, PCI may be
      administered concurrently with atezolizumab and dendritic cell vaccination during the
      maintenance part. For those patients who have not progressed at the time of study drug
      discontinuation, the tumor assessments (including all disease locations) will be assessed
      radiologically by CT or MRI, as performed at screening, every 9 weeks (approximately 63 ± 7
      days), until the occurrence of PD or study completion. The same method of assessment (CT or
      MRI) should be used to characterize tumors at screening and at all follow-up assessments. If
      positron emission tomography (PET) is used, it should also be accompanied by spiral CT or
      MRI.

      Safety will be defined based on the rate of serious adverse events (SAEs) comparing with
      historic controls of atezolizumab in monotherapy as a maintenance treatment.

      Kaplan Meier method will be used to estimate the survival function. Translational study

      Tumor samples: All patients will undergo baseline tumor tissue acquisition prior to
      enrollment. The only mandatory tissue biopsy is pretreatment. Tissue samples:

      Pre induction treatment fresh and paraffin-embedded tumor sample (If obtaining a fresh biopsy
      is not feasible, the case should be discussed with Coordinating Investigators) Pre
      maintenance phase (for those that rebiopsy is feasible) After 24 weeks on maintenance phase
      (for those patents that continue on treatment after w24 on maintenance and rebiopsy is
      feasible) At tumor progression (for those patients who progressed and rebiopsy is feasible).

      Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA
      expression, WES analysis, and flow cytometry in pretreatment fresh tumor tissue.

      Peripheral blood samples: Peripheral blood samples will be collected:

      Pre induction treatment Pre maintenance phase After 9 weeks of the first vaccination At
      progression of the disease The analysis will consist of T cell immunophenotyping, DC
      immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by
      WES and cytokine analysis
allocation: N/A
intervention model: Single Group Assignment
intervention model description: single arm Phase Ib/II multicenter open label study, with translational sub-study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival (PFS) rate at 6 months
time frame: At 6 months after start of treatment
description: Calculated as the percentage of participants alive and without disease progression, as assessed by the Investigator using RECIST v1.1
measure: Frequency and severity of AEs and SAEs (Safety)
time frame: Throughout the study. Approximately 3 years
description: he number of patients with AEs and SAEs, changes in laboratory values, vital signs, ECGs, and results of physician examinations graded according to the CTCAE v 5.0.
measure: Duration of clinical benefit (DCB) as per RECIST 1.1
time frame: Throughout the study. Approximately 3 years
description: DCB calculated as the time (in months) from first dose of treatment to progression (or death from any cause) in patients who had a best overall response of CR, PR, or SD of ≥ 24 weeks.
measure: Overall Survival (OS)
time frame: Throughout the study. Approximately 3 years
description: Median Overall Survival (mOS) is calculated as the time from date of inclusion to date of death due to any cause.
measure: Objective response rate (ORR1) as per RECIST 1.1
time frame: Throughout the study. Approximately 3 years
description: Rate of patients that achieve partial or complete response as best response during study induction treatment
measure: Objective response rate (ORR2) as per RECIST 1.1
time frame: Throughout the study. Approximately 3 years
description: Rate of patients that have a further best response during maintenance treatment
arm group label: Atezo+DCvac
arm group type: Experimental
description: - Induction (4 cycles, every 3 weeks): Carboplatin area under the curve (AUC) 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle) Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)
- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks) DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.
intervention type: Drug
intervention name: Atezolizumab 1200 mg in 20 ML Injection
description: - Induction (4 cycles, every 3 weeks): Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)
- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks)
arm group label: Atezo+DCvac
other name: Tecentriq
intervention type: Biological
intervention name: ADC Vaccine
description: - Maintenance (only patients without PD after 4 induction cycles, up to PD): DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.
arm group label: Atezo+DCvac
other name: Autologous Dendritic cell (ADC) vaccine, Dendritic cell (DC) vaccine
intervention type: Drug
intervention name: Carboplatin
description: - Induction (4 cycles, every 3 weeks): Carboplatin AUC 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle)
arm group label: Atezo+DCvac
other name: Carboplatino (Teva/Accord/Pharmacia)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: María González Cao
role: Study Chair
affiliation: Hospital Quirón-Dexeus
last name: A responsible person designated by the sponsor
phone: 93 434 44 12
email: investigacion@mfar.net
last name: Responsible person designated by the sponsor
phone: 93 434 44 12
email: investigacion@mfar.net
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Spain
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
mesh term: Carboplatin
mesh term: Atezolizumab
mesh term: Vaccines
sharing ipd: No