<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/NCT03834233</url>
  </required_header>
  <id_info>
    <org_study_id>1258/18</org_study_id>
    <nct_id>NCT03834233</nct_id>
  </id_info>
  <brief_title>Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma</brief_title>
  <acronym>CA209-9JC</acronym>
  <official_title>A Phase II of Study of Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto do Cancer do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto do Cancer do Estado de São Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent malignancies worldwide,&#xD;
      and an increasing incidence has been documented over the past decades. Despite optimal&#xD;
      initial approach, which can be curative in the majority of cases, a proportion of patients&#xD;
      present with locally advanced or unresectable disease, leading to significant morbidity. In&#xD;
      addition, metastases of cSCC may affect 2 to 5% of individuals diagnosed with this disease.&#xD;
      In the setting of advanced cSCC, no standard systemic treatment has been established, and&#xD;
      treatment options are frequently adapted from those applied to squamous cell carcinoma&#xD;
      arising from other sites, based on a low level of evidence and often with short-lived&#xD;
      benefits.&#xD;
&#xD;
      cSCC are potentially immunogenic neoplasms with an unmet need for therapeutic options, having&#xD;
      sun exposure and chronic inflammation as the most significant risk factors. Using the&#xD;
      anti-PD1 monoclonal antibody nivolumab to treat patients with cSCC and planned scientific&#xD;
      correlates, investigators believe that the safety and efficacy of immune activating therapy&#xD;
      for this disease can be assessed.&#xD;
&#xD;
      This is a multi-center, Simon two-stage, phase II study to evaluate the safety and efficacy&#xD;
      of the anti-PD1 monoclonal antibody nivolumab for systemic-treatment-naïve patients with&#xD;
      metastatic and/or locally advanced cSCC.&#xD;
&#xD;
      The primary objective of the study is to evaluate the efficacy, as assessed by the best&#xD;
      objective response rate (complete response + partial response) at 24 weeks according to&#xD;
      RECIST criteria, of nivolumab in patients with advanced cSCC. Secondary objectives are to&#xD;
      assess the safety/tolerability of the treatment, to determine the progression-free survival&#xD;
      (PFS) and overall survival (OS) rates at 24 weeks, and to evaluate the objective response&#xD;
      rate as assessed by immune-related response criteria (irRC). Treatment will be given every 14&#xD;
      days until disease progression, unacceptable toxicity or withdrawal of consent/patient&#xD;
      decision. If the patient continues to benefit from treatment with nivolumab, treatment will&#xD;
      be continued for up to 12 months. Patients will be reassessed at week 12 and every 12 weeks&#xD;
      thereafter until week 52, and then as per discretion of the treating investigator. A tumor&#xD;
      biopsy will be performed before treatment initiation, unless contraindicated and optional&#xD;
      biopsies will be performed at week 13 and following disease progression. Serial blood samples&#xD;
      will be obtained at baseline, during, and after treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 5, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Actual">December 1, 2019</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 objective response rate (complete response + partial response) using RECIST criteria at 24 weeks</measure>
    <time_frame>From date of treatment initiation until week 24</time_frame>
    <description>To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by RECIST 1.1, of nivolumab in patients with advanced cSCC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment related adverse events</measure>
    <time_frame>From date of treatment initiation until week 24</time_frame>
    <description>To assess the safety and tolerability of nivolumab in patients with advanced cSCC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) rate</measure>
    <time_frame>From date of treatment initiation until week 24</time_frame>
    <description>To determine the progression free survival (PFS) rate at 24 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best objective response rate (complete response + partial response) using immune-related response criteria</measure>
    <time_frame>From date of treatment initiation until week 24</time_frame>
    <description>To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by immune-related response criteria (irRC), of nivolumab in patients with advanced cSCC.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Advanced Cutaneous Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab 3mg/kg IV every 14 days until disease progression, unacceptable toxicity or up to 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 3mg/kg IV every 14 days until disease progression, unacceptable toxicity or up to 12 months.</description>
    <arm_group_label>Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or females at least 18 years of age.&#xD;
&#xD;
          -  Subjects must have a histologically confirmed metastatic/locally advanced cutaneous&#xD;
             squamous cell carcinoma&#xD;
&#xD;
          -  No prior systemic treatments for advanced (metastatic or locally advanced) cSCC&#xD;
&#xD;
          -  Measurable disease as defined by RECIST 1.1&#xD;
&#xD;
          -  Performance status: ECOG 0 to 1&#xD;
&#xD;
          -  Patients must be recovered from surgery or toxic effects of prior radiation therapy.&#xD;
             Study treatment may not start until at least two weeks from completion of radiation&#xD;
             therapy or surgery.&#xD;
&#xD;
          -  Adequate hematologic, hepatic and renal function as defined below i. Hemoglobin &gt; 8.5&#xD;
             g/dl (can be post transfusion) ii. Absolute neutrophil count &gt; 1,000/mm3 iii. Platelet&#xD;
             count &gt; 75,000/mm3 iv. Total Bilirubin &lt;2.0 x upper limit of normal (ULN) in absence&#xD;
             of Gilbert disease (Total Bilirubin ≤ 3 x ULN with Gilbert).&#xD;
&#xD;
             v. ALT (SGOT) or AST (SGPT) &lt;2.0 x ULN (or &lt; 3 times the upper limit of normal are&#xD;
             permitted if clearly attributed to liver metastasis) vi. Calculated creatinine&#xD;
             clearance (CrCI) ≥ 30 mL/min using the lean body mass formula only (Modified Cockroft&#xD;
             and Gault; Shargel and Yu 1985)&#xD;
&#xD;
          -  Ability to understand informed consent and comply with treatment protocol&#xD;
&#xD;
          -  Male and female patients with reproductive potential must use an approved&#xD;
             contraceptive method if appropriate (eg, intrauterine device [IUD], birth control&#xD;
             pills, or barrier device) during and for 5 months (females) or 7 months (males) after&#xD;
             the study. Women of childbearing potential (WOCBP) must have a negative serum&#xD;
             pregnancy test within 30 days prior to study enrollment. Men of fathering potential&#xD;
             must be using an adequate method of contraception to avoid conception throughout the&#xD;
             study and for 7 months following the last dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior use of anti-PD-1 or anti-PD-L1 monoclonal antibody.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including active infection or symptomatic congestive&#xD;
             heart failure within 6 months&#xD;
&#xD;
          -  Patients requiring systemic treatment with corticosteroids (&gt;10mg daily of prednisone&#xD;
             or equivalent) or using immunosuppressive medications within 10 days of study drug&#xD;
             administration.&#xD;
&#xD;
          -  Patients with untreated or symptomatic brain metastases.&#xD;
&#xD;
          -  Known history of immunodeficiency virus disease with detectable viral load and CD4+&#xD;
             lymphocyte count &lt;350 mm3. Patients with undetectable vital load and CD4+ lymphocyte&#xD;
             count &gt;350 mm3 are eligible&#xD;
&#xD;
          -  History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis,&#xD;
             vasculitis, or other symptomatic autoimmune disease, or documented history of&#xD;
             autoimmune disease or syndrome requiring systemic steroids or immunosuppressive agents&#xD;
             except vitiligo or resolved childhood asthma/atopy.&#xD;
&#xD;
          -  Evidence of clinically significant immunosuppression, including primary&#xD;
             immunodeficiency state such as Severe Combined Immunodeficiency Disease or concurrent&#xD;
             opportunistic infection&#xD;
&#xD;
          -  Known active hepatitis B or hepatitis C infection. Patients with undetectable viral&#xD;
             load for hepatitis B or C as determined by PCR are eligible.&#xD;
&#xD;
          -  History of stem-cell or solid organ transplant.&#xD;
&#xD;
          -  Received live vaccine within 28 days prior to enrollment&#xD;
&#xD;
          -  Female subject is pregnant or breast-feeding, or planning to become pregnant during&#xD;
             study treatment and through 5 months after the last dose of nivolumab.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rodrigo Ramella Munhoz</name>
      <address>
        <city>São Paulo</city>
        <zip>01346000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>February 3, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto do Cancer do Estado de São Paulo</investigator_affiliation>
    <investigator_full_name>Rodrigo R Munhoz</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</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/NCT03834233
org study id: 1258/18
nct id: NCT03834233
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent malignancies worldwide,
      and an increasing incidence has been documented over the past decades. Despite optimal
      initial approach, which can be curative in the majority of cases, a proportion of patients
      present with locally advanced or unresectable disease, leading to significant morbidity. In
      addition, metastases of cSCC may affect 2 to 5% of individuals diagnosed with this disease.
      In the setting of advanced cSCC, no standard systemic treatment has been established, and
      treatment options are frequently adapted from those applied to squamous cell carcinoma
      arising from other sites, based on a low level of evidence and often with short-lived
      benefits.

      cSCC are potentially immunogenic neoplasms with an unmet need for therapeutic options, having
      sun exposure and chronic inflammation as the most significant risk factors. Using the
      anti-PD1 monoclonal antibody nivolumab to treat patients with cSCC and planned scientific
      correlates, investigators believe that the safety and efficacy of immune activating therapy
      for this disease can be assessed.

      This is a multi-center, Simon two-stage, phase II study to evaluate the safety and efficacy
      of the anti-PD1 monoclonal antibody nivolumab for systemic-treatment-naïve patients with
      metastatic and/or locally advanced cSCC.

      The primary objective of the study is to evaluate the efficacy, as assessed by the best
      objective response rate (complete response + partial response) at 24 weeks according to
      RECIST criteria, of nivolumab in patients with advanced cSCC. Secondary objectives are to
      assess the safety/tolerability of the treatment, to determine the progression-free survival
      (PFS) and overall survival (OS) rates at 24 weeks, and to evaluate the objective response
      rate as assessed by immune-related response criteria (irRC). Treatment will be given every 14
      days until disease progression, unacceptable toxicity or withdrawal of consent/patient
      decision. If the patient continues to benefit from treatment with nivolumab, treatment will
      be continued for up to 12 months. Patients will be reassessed at week 12 and every 12 weeks
      thereafter until week 52, and then as per discretion of the treating investigator. A tumor
      biopsy will be performed before treatment initiation, unless contraindicated and optional
      biopsies will be performed at week 13 and following disease progression. Serial blood samples
      will be obtained at baseline, during, and after treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best objective response rate (complete response + partial response) using RECIST criteria at 24 weeks
time frame: From date of treatment initiation until week 24
description: To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by RECIST 1.1, of nivolumab in patients with advanced cSCC.
measure: Incidence of treatment related adverse events
time frame: From date of treatment initiation until week 24
description: To assess the safety and tolerability of nivolumab in patients with advanced cSCC.
measure: Progression free survival (PFS) rate
time frame: From date of treatment initiation until week 24
description: To determine the progression free survival (PFS) rate at 24 weeks
measure: Best objective response rate (complete response + partial response) using immune-related response criteria
time frame: From date of treatment initiation until week 24
description: To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by immune-related response criteria (irRC), of nivolumab in patients with advanced cSCC.
arm group label: Nivolumab
arm group type: Experimental
description: Nivolumab 3mg/kg IV every 14 days until disease progression, unacceptable toxicity or up to 12 months.
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 3mg/kg IV every 14 days until disease progression, unacceptable toxicity or up to 12 months.
arm group label: Nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Instituto do Cancer do Estado de São Paulo
investigator full name: Rodrigo R Munhoz
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Nivolumab
sharing ipd: Undecided