<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/NCT03823625</url>
  </required_header>
  <id_info>
    <org_study_id>SQUINT-FoRT 04</org_study_id>
    <nct_id>NCT03823625</nct_id>
  </id_info>
  <brief_title>An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)</brief_title>
  <acronym>SQUINT</acronym>
  <official_title>SQUINT (Squamous Immunotherapy Nivolumab-Ipilimumab Trial): An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Ricerca Traslazionale</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinical Research Technology S.r.l.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione Ricerca Traslazionale</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Non-small-cell Lung Cancer (NSCLC) remains the leading cause of cancer death in Western&#xD;
      Countries. Approximately 85% of lung cancers are of the non-small-cell type (NSCLC), with&#xD;
      25-30% of NSCLC being squamous histology type. Unlike nonsquamous NSCLC, squamous NSCLC&#xD;
      rarely harbors epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)&#xD;
      mutations for which there are directed therapies, and until the recent approval of&#xD;
      immunotherapies for pretreated squamous NSCLC, a limited number of traditional cytotoxic&#xD;
      chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic&#xD;
      squamous NSCLC. A platinum-based combination chemotherapy regimen has been the standard&#xD;
      first-line treatment for all NSCLC. Carboplatin is frequently substituted for cisplatin for&#xD;
      patients who have poor renal function or who experience toxicities from cisplatin (most&#xD;
      notably, nausea and vomiting). Taxanes, especially paclitaxel, or vinorelbine or gemcitabine,&#xD;
      commonly complete the standard two-drug backbone of platinum-based chemotherapy for the&#xD;
      first-line treatment of NSCLC, with platin-gemcitabine as the most commonly used regimen in&#xD;
      Europe in patients with squamous-histology. A recent press release announced that&#xD;
      pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy&#xD;
      alone in patients with squamous-cell lung cancer. Nevertheless, no data on Progression-Free&#xD;
      Survival (PFS) and Overall Survival (OS) are available. Therefore, considering the lack of&#xD;
      data in patients with squamous histology and the lack of information about efficacy of&#xD;
      combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus&#xD;
      chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such&#xD;
      strategies in patients with advanced, metastatic squamous-cell lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Better understanding of the role of the immunological system in tumor control has opened&#xD;
      multiple doors to implement different strategies to enhance immune response against cancer&#xD;
      cells. It is known that tumor cells elude immune response by several mechanisms. The&#xD;
      development of monoclonal antibodies against the checkpoint inhibitor programmed cell death&#xD;
      protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer&#xD;
      patients with long lasting responses. In the KEYNOTE 024 the anti-PD-1 inhibitor&#xD;
      Pembrolizumab significantly prolonged progression-free survival (PFS) and overall survival&#xD;
      (OS) of patients with advanced NSCLC and high PD-L1 level (&gt;50% of tumor cells) compared to&#xD;
      platinum based chemotherapy, thus becoming a new standard of care in front line setting.&#xD;
      However, the trial was not restricted to squamous population, with approximately 18% per arm&#xD;
      having this histology. Nivolumab, another PD-1 inhibitor, has been recently approved for the&#xD;
      treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in&#xD;
      a phase III trial comparing the drug to docetaxel, in second-line setting. Importantly, the&#xD;
      benefit produced by the drug was irrespective of PD-L1 expression suggesting that the high&#xD;
      mutation burden of squamous-cell lung carcinoma is more relevant than the expression of a&#xD;
      single biomarker, at least in pretreated individuals. In addition, recent studies in chemo&#xD;
      naive patients with non-squamous histology demonstrated that combination of chemotherapy and&#xD;
      immunotherapy is superior to chemotherapy alone in terms of Overall Survival irrespective of&#xD;
      PD-L1 expression (Keynote 189 and IMPOWER 150). In addition, the CheckMate 227 study recently&#xD;
      showed that, in chemonaive NSCLC, combination of nivolumab and ipilimumab was superior to&#xD;
      chemotherapy alone in patients with high tumor mutational burden (TMB), irrespective of PD-L1&#xD;
      expression. A recent press release announced that pembrolizumab plus chemotherapy produced&#xD;
      higher response rate when compared to chemotherapy alone in patients with squamous-cell lung&#xD;
      cancer (Keynote 407). Nevertheless, no data on Progression-Free Survival and Overall Survival&#xD;
      are available. Therefore, considering the lack of data in patients with squamous histology&#xD;
      and the lack of information about efficacy of combinations of immune-checkpoints inhibitors&#xD;
      versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for&#xD;
      conducting a study assessing efficacy of such strategies in patients with advanced,&#xD;
      metastatic squamous-cell lung cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Anticipated">February 28, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Open-label, randomized, phase II trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy in terms of Overall Survival in subjects with Stage IIIB not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma treated in the study</measure>
    <time_frame>12 months</time_frame>
    <description>Overall Survival rate at 12 months in Arm A and B</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarkers analysis</measure>
    <time_frame>48 months</time_frame>
    <description>Correlation of PD-L1 expression and/or TMB with outcome in Arm A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>48 months</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">112</enrollment>
  <condition>Squamous-Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>ARM A: Nivolumab plus Ipilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months. Platinum-based chemotherapy will be given up to 6 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM B: Platinum-based chemotherapy plus Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Platinum-based chemotherapy will be given up to 6 cycles. Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab plus Ipilimumab</intervention_name>
    <description>Nivolumab will be administered at the standard dose of 360 mg every 3 weeks. Ipilimumab will be administered at the dose of 1 mg/kg every 6 weeks.</description>
    <arm_group_label>ARM A: Nivolumab plus Ipilimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Platinum-based chemotherapy plus Nivolumab</intervention_name>
    <description>Nivolumab will be administered at the standard dose of 360 mg every 3 weeks.&#xD;
Platinum-based chemotherapy will be chosen by the investigator among the following regimens:&#xD;
Cisplatin 80 mg/mq iv day 1 and Gemcitabine 1250 mg/mq iv days 1 and 8 every 21 days;&#xD;
Carboplatin AUC 5 iv day 1 and Gemcitabine 1000 mg/mq iv days 1 and 8 iv every 21 days;&#xD;
Carboplatin AUC 6 iv day 1 and paclitaxel 200 mg/mq iv day 1 every 21 days.</description>
    <arm_group_label>ARM B: Platinum-based chemotherapy plus Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients willing and able to give written informed consent;&#xD;
&#xD;
          -  Histologically confirmed diagnosis of Stage IIIB-not amenable to radical treatment or&#xD;
             Stage IV or recurrent squamous-cell lung carcinoma;&#xD;
&#xD;
          -  Tumor p63 (or p40) positive and TTF1 negative;&#xD;
&#xD;
          -  Availability of tumor tissue for PD-L1 expression analysis. One formalin-fixed&#xD;
             paraffin embedded tumor tissue block or a minimum of 16 unstained tumor tissue&#xD;
             sections are acceptable. The tumor tissue sample may be fresh or archival if obtained&#xD;
             within 6 months prior to enrollment, and there can have been no systemic therapy (eg,&#xD;
             adjuvant or neoadjuvant chemotherapy) given after the sample was obtained. Tissue must&#xD;
             be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies or&#xD;
             drainage of pleural effusions with cytospins are not considered adequate for biomarker&#xD;
             review. Biopsies of bone lesions that do not have a soft tissue component or&#xD;
             decalcified bone tumor samples are also not acceptable;&#xD;
&#xD;
          -  Availability of PD-L1 status;&#xD;
&#xD;
          -  Chemonaive patient. Adjuvant/neoadjuvant chemotherapy is allowed if therapy was&#xD;
             completed at least 6 months before trial inclusion;&#xD;
&#xD;
          -  Performance status 0-1 (ECOG);&#xD;
&#xD;
          -  Patient compliance to trial procedures;&#xD;
&#xD;
          -  Age ≥ 18 years;&#xD;
&#xD;
          -  Written informed consent;&#xD;
&#xD;
          -  Adequate BM function (ANC ≥ 1.5x109/L, Platelets ≥ 100x109/L, HgB &gt; 9g/dl);&#xD;
&#xD;
          -  Adequate liver function (bilirubin &lt; G2, transaminases no more than 3xULN/&lt;5xULN in&#xD;
             present of liver metastases);&#xD;
&#xD;
          -  Normal level of alkaline phosphatase and creatinine;&#xD;
&#xD;
          -  If female: childbearing potential either terminated by surgery, radiation, or&#xD;
             menopause, or attenuated by use of approved contraceptive method [intrauterine&#xD;
             contraceptive device (IUD), birth control pills, or barrier device] during and for&#xD;
             twenty-three (23) weeks after end of treatment;&#xD;
&#xD;
          -  If men who are sexually active with WOCBP must use any contraceptive method with a&#xD;
             failure rate of less than 1% per year. Men receiving nivolumab and who are sexually&#xD;
             active with WOCBP will be instructed to adhere to contraception for a period of 31&#xD;
             weeks after the last dose of investigational product;&#xD;
&#xD;
          -  Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2&#xD;
             weeks prior to treatment. Patients with symptomatic tumor lesions that may require&#xD;
             palliative radiotherapy within 4 weeks of first treatment are strongly encouraged to&#xD;
             receive palliative radiotherapy prior to treatment. Patients are eligible if CNS&#xD;
             metastases are adequately treated and patients are neurologically returned to baseline&#xD;
             (except for residual signs or symptoms related to the CNS treatment) for at least 2&#xD;
             weeks prior to randomization;&#xD;
&#xD;
          -  Patients must be either off corticosteroids, or on a stable or decreasing dose of ≥10&#xD;
             mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No tumor tissue available;&#xD;
&#xD;
          -  Tumor negative for p63 (or p40) or positive for TTF1;&#xD;
&#xD;
          -  Previous chemotherapy for stage IV disease;&#xD;
&#xD;
          -  Adjuvant or neoadjuvant chemotherapy completed less than 6 months before trial&#xD;
             inclusion; adjuvant or neoadjuvant immunotherapy is not allowed;&#xD;
&#xD;
          -  Concomitant radiotherapy or chemotherapy;&#xD;
&#xD;
          -  Untreated brain metastases;&#xD;
&#xD;
          -  Diagnosis of any other malignancy during the last 2 years, except for in situ&#xD;
             carcinoma of cervix uteri and cutaneous squamous cell carcinoma;&#xD;
&#xD;
          -  Pregnancy or lactating;&#xD;
&#xD;
          -  Other serious illness or medical condition potentially interfering with the study.&#xD;
&#xD;
        Nivolumab and ipilimumab specific exclusion&#xD;
&#xD;
          -  Patients with an active, known or suspected autoimmune disease. Patients with type I&#xD;
             diabetes mellitus; hypothyroidism only requiring hormone replacement, skin disorders&#xD;
             (such as vitiligo, psoriasis, or alopecia) requiring systemic treatment, or conditions&#xD;
             not expected to recur in the absence of an external trigger are permitted to enroll;&#xD;
&#xD;
          -  Patients with a condition requiring systemic treatment with either corticosteroids (&gt;&#xD;
             10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of randomization. Inhaled or topical steroids, and adrenal replacement steroid &gt;&#xD;
             10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune&#xD;
             disease;&#xD;
&#xD;
          -  Patients should be excluded if they are positive test for hepatitis B virus surface&#xD;
             antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating&#xD;
             acute or chronic infection;&#xD;
&#xD;
          -  Patients should be excluded if they have known history of testing positive for human&#xD;
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).&#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>Federico Cappuzzo</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale di Ravenna</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Federico Cappuzzo</last_name>
    <phone>0544285206</phone>
    <email>f.cappuzzo@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica</name>
      <address>
        <city>Meldola</city>
        <state>Forlì- Cesena</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angelo Delmonte, MD</last_name>
      <phone>+39 0543739100</phone>
      <email>angelo.delmonte@irst.emr.it</email>
    </contact>
    <investigator>
      <last_name>Angelo Delmonte, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;Infermi&quot; Rimini</name>
      <address>
        <city>Rimini</city>
        <state>Italia</state>
        <zip>47900</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maximilian Papi, MD</last_name>
      <email>maximilian.papi@auslromagna.it</email>
    </contact>
    <contact_backup>
      <phone>0541705413</phone>
    </contact_backup>
    <investigator>
      <last_name>Maximilian Papi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centro di Riferimento Oncologico della Basilicata</name>
      <address>
        <city>Rionero In Vulture</city>
        <state>Potenza</state>
        <zip>85028</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Aieta</last_name>
      <phone>+39 0972726429</phone>
      <email>michele.aieta@crob.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica</name>
      <address>
        <city>Negrar</city>
        <state>Verona</state>
        <zip>37024</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefania Gori, MD</last_name>
      <phone>+39 0456013472</phone>
      <email>stefania.gori@sacrocuore.it</email>
    </contact>
    <investigator>
      <last_name>Stefania Gori, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8</name>
      <address>
        <city>Arezzo</city>
        <zip>52100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sergio Bracarda</last_name>
      <phone>+39 0575255438</phone>
      <email>sergio.bracarda@usl8.toscana.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Francesco Grossi</last_name>
      <phone>+39 0105600385</phone>
      <email>fg1965@libero.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia - Divisione di Oncologia Toracica</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Filippo De Marinis, MD</last_name>
      <phone>+39 0257489482</phone>
      <email>Filippo.DeMarinis@ieo.it</email>
    </contact>
    <investigator>
      <last_name>Filippo De Marinis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fausto Barbieri, MD</last_name>
      <phone>+39 0594224385</phone>
      <email>barbieri.fausto@policlinico.mo.it</email>
    </contact>
    <investigator>
      <last_name>Fausto Barbieri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.R.N dei Colli - Ospedale Monaldi</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>I.R.C.C.S. Istituto Oncologico Veneto</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura Bonanno, MD</last_name>
      <phone>+39 0498215553</phone>
      <email>laura.bonanno@ioveneto.it</email>
    </contact>
    <investigator>
      <last_name>Laura Bonanno, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Paolo Giaccone</name>
      <address>
        <city>Palermo</city>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Casa di Cura La Maddalena- U.O. Oncologia medica</name>
      <address>
        <city>Palermo</city>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vittorio Gebbia</last_name>
      <phone>+39 0916806111</phone>
      <email>vittorio.gebbia@tin.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Perugia- S.C. Oncologia Medica</name>
      <address>
        <city>Perugia</city>
        <zip>06132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincenzo Minotti, MD</last_name>
      <phone>0755784099</phone>
      <email>vinminotti@yahoo.it</email>
    </contact>
    <investigator>
      <last_name>Vincenzo Minotti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale di Ravenna- Oncologia Medica</name>
      <address>
        <city>Ravenna</city>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Federico Cappuzzo, MD</last_name>
      <phone>+39 0544285247</phone>
      <email>f.cappuzzo@googlemail.com</email>
    </contact>
    <investigator>
      <last_name>Federico Cappuzzo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IRCCS Arcispedale Santa Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <zip>42123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesca Zanelli, MD</last_name>
      <phone>+39 0522296602</phone>
      <email>zanelli.francesca@asmn.re.it</email>
    </contact>
    <investigator>
      <last_name>Francesca Zanelli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera San Camillo-Forlanini</name>
      <address>
        <city>Roma</city>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario &quot;Campus Biomedico&quot; di Roma</name>
      <address>
        <city>Roma</city>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Daniele Santini</last_name>
      <phone>+ 39 06225411344</phone>
      <email>d.santini@unicampus.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>February 2, 2018</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SqLC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03823625
org study id: SQUINT-FoRT 04
nct id: NCT03823625
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
Non-small-cell Lung Cancer (NSCLC) remains the leading cause of cancer death in Western
      Countries. Approximately 85% of lung cancers are of the non-small-cell type (NSCLC), with
      25-30% of NSCLC being squamous histology type. Unlike nonsquamous NSCLC, squamous NSCLC
      rarely harbors epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)
      mutations for which there are directed therapies, and until the recent approval of
      immunotherapies for pretreated squamous NSCLC, a limited number of traditional cytotoxic
      chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic
      squamous NSCLC. A platinum-based combination chemotherapy regimen has been the standard
      first-line treatment for all NSCLC. Carboplatin is frequently substituted for cisplatin for
      patients who have poor renal function or who experience toxicities from cisplatin (most
      notably, nausea and vomiting). Taxanes, especially paclitaxel, or vinorelbine or gemcitabine,
      commonly complete the standard two-drug backbone of platinum-based chemotherapy for the
      first-line treatment of NSCLC, with platin-gemcitabine as the most commonly used regimen in
      Europe in patients with squamous-histology. A recent press release announced that
      pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy
      alone in patients with squamous-cell lung cancer. Nevertheless, no data on Progression-Free
      Survival (PFS) and Overall Survival (OS) are available. Therefore, considering the lack of
      data in patients with squamous histology and the lack of information about efficacy of
      combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus
      chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such
      strategies in patients with advanced, metastatic squamous-cell lung cancer.
Better understanding of the role of the immunological system in tumor control has opened
      multiple doors to implement different strategies to enhance immune response against cancer
      cells. It is known that tumor cells elude immune response by several mechanisms. The
      development of monoclonal antibodies against the checkpoint inhibitor programmed cell death
      protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer
      patients with long lasting responses. In the KEYNOTE 024 the anti-PD-1 inhibitor
      Pembrolizumab significantly prolonged progression-free survival (PFS) and overall survival
      (OS) of patients with advanced NSCLC and high PD-L1 level (>50% of tumor cells) compared to
      platinum based chemotherapy, thus becoming a new standard of care in front line setting.
      However, the trial was not restricted to squamous population, with approximately 18% per arm
      having this histology. Nivolumab, another PD-1 inhibitor, has been recently approved for the
      treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in
      a phase III trial comparing the drug to docetaxel, in second-line setting. Importantly, the
      benefit produced by the drug was irrespective of PD-L1 expression suggesting that the high
      mutation burden of squamous-cell lung carcinoma is more relevant than the expression of a
      single biomarker, at least in pretreated individuals. In addition, recent studies in chemo
      naive patients with non-squamous histology demonstrated that combination of chemotherapy and
      immunotherapy is superior to chemotherapy alone in terms of Overall Survival irrespective of
      PD-L1 expression (Keynote 189 and IMPOWER 150). In addition, the CheckMate 227 study recently
      showed that, in chemonaive NSCLC, combination of nivolumab and ipilimumab was superior to
      chemotherapy alone in patients with high tumor mutational burden (TMB), irrespective of PD-L1
      expression. A recent press release announced that pembrolizumab plus chemotherapy produced
      higher response rate when compared to chemotherapy alone in patients with squamous-cell lung
      cancer (Keynote 407). Nevertheless, no data on Progression-Free Survival and Overall Survival
      are available. Therefore, considering the lack of data in patients with squamous histology
      and the lack of information about efficacy of combinations of immune-checkpoints inhibitors
      versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for
      conducting a study assessing efficacy of such strategies in patients with advanced,
      metastatic squamous-cell lung cancer.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open-label, randomized, phase II trial
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy in terms of Overall Survival in subjects with Stage IIIB not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma treated in the study
time frame: 12 months
description: Overall Survival rate at 12 months in Arm A and B
measure: Biomarkers analysis
time frame: 48 months
description: Correlation of PD-L1 expression and/or TMB with outcome in Arm A and B
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 48 months
description: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
arm group label: ARM A: Nivolumab plus Ipilimumab
arm group type: Experimental
description: Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months. Platinum-based chemotherapy will be given up to 6 cycles.
arm group label: ARM B: Platinum-based chemotherapy plus Nivolumab
arm group type: Experimental
description: Platinum-based chemotherapy will be given up to 6 cycles. Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months.
intervention type: Drug
intervention name: Nivolumab plus Ipilimumab
description: Nivolumab will be administered at the standard dose of 360 mg every 3 weeks. Ipilimumab will be administered at the dose of 1 mg/kg every 6 weeks.
arm group label: ARM A: Nivolumab plus Ipilimumab
intervention type: Drug
intervention name: Platinum-based chemotherapy plus Nivolumab
description: Nivolumab will be administered at the standard dose of 360 mg every 3 weeks.
Platinum-based chemotherapy will be chosen by the investigator among the following regimens:
Cisplatin 80 mg/mq iv day 1 and Gemcitabine 1250 mg/mq iv days 1 and 8 every 21 days;
Carboplatin AUC 5 iv day 1 and Gemcitabine 1000 mg/mq iv days 1 and 8 iv every 21 days;
Carboplatin AUC 6 iv day 1 and paclitaxel 200 mg/mq iv day 1 every 21 days.
arm group label: ARM B: Platinum-based chemotherapy plus Nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Federico Cappuzzo
role: Principal Investigator
affiliation: Ospedale di Ravenna
last name: Federico Cappuzzo
phone: 0544285206
email: f.cappuzzo@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Active, not recruiting
country: Italy
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Nivolumab
mesh term: Ipilimumab
sharing ipd: Undecided