<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/NCT03774901</url>
  </required_header>
  <id_info>
    <org_study_id>P/2017/337</org_study_id>
    <secondary_id>2018-001427-38</secondary_id>
    <nct_id>NCT03774901</nct_id>
  </id_info>
  <brief_title>Maintenance Avelumab Immunotherapy in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma</brief_title>
  <acronym>PULSE</acronym>
  <official_title>Activity and Tolerability of Maintenance Avelumab Immunotherapy After First Line Polychemotherapy Including Platinum in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Besancon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Besancon</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>
      Patients with unresectable locally advanced or metastatic squamous cell penile carcinoma&#xD;
      (SPC) who are in response or with stable disease after first line platinum containing&#xD;
      polychemotherapy who meet the inclusion/exclusion criteria will be offered to take part in&#xD;
      the study.&#xD;
&#xD;
      The patients may be pre-screened at the time of the 1st line chemotherapy.&#xD;
&#xD;
      In order for patients to be enrolled, the investigator must have carried out a radiological&#xD;
      assessment of the disease during first line systemic treatment (a maximum of between 3 and 6&#xD;
      cycles): the cancer must be controlled. Patients with disease progression cannot be included&#xD;
      in the PULSE study as this is a maintenance study.&#xD;
&#xD;
      After inclusion, Avelumab will be administered at a dose of 10 mg/kg, at a frequency of once&#xD;
      every 2 weeks with appropriate supportive care.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 12, 2019</start_date>
  <completion_date type="Anticipated">September 22, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 22, 2024</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>PFS (progression-free survival)</measure>
    <time_frame>24 months</time_frame>
    <description>To estimate progression-free survival in patients included in this study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS (overall survival)</measure>
    <time_frame>32 months</time_frame>
    <description>To estimate overall survival in patients included in this study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MDT (median duration of treatment)</measure>
    <time_frame>24 months</time_frame>
    <description>To estimate the median duration of avelumab treatment calculated from avelumab initiation in patients included in this study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QOL (quality of life) assessed by EORTC QLQ-C30</measure>
    <time_frame>24 months</time_frame>
    <description>To assess health-related quality of life since avelumab is started in patients included in this study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.03</measure>
    <time_frame>24 months</time_frame>
    <description>To assess safety profile after avelumab initiation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Penile Cancer</condition>
  <condition>Penile Neoplasms</condition>
  <condition>Penile Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>avelumab maintenance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab will be administered at a dose of 10 mg/kg every 2 weeks with appropriate supportive care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>intravenous 10 mg/kg every 2 weeks</description>
    <arm_group_label>avelumab maintenance</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Eligibility Criteria&#xD;
&#xD;
        Inclusion:&#xD;
&#xD;
          -  Histologically confirmed unresectable locally advanced or metastatic squamous cell&#xD;
             penile carcinoma&#xD;
&#xD;
          -  Patients who have received a minimum of 3 and a maximum of 6 cycles of&#xD;
             polychemotherapy including a platinum (cisplatin or carboplatin) administered as 1st&#xD;
             line systemic treatment.&#xD;
&#xD;
        In the event of pretreatment with cisplatin: a cumulative minimum dose of 210 mg/m2 is&#xD;
        required in order to be eligible.&#xD;
&#xD;
        In the event of pretreatment with carboplatin: a minimum cumulative dose equivalent to 3&#xD;
        cycles of carboplatin AUC5 is required to be eligible&#xD;
&#xD;
          -  Patients without disease-progression according to the RECIST v1.1 criteria (i.e. in&#xD;
             complete or partial response or stable disease at inclusion) after 3 to 6 cycles of&#xD;
             1st line chemotherapy.&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Group) performance status of 0 to 2&#xD;
&#xD;
          -  Adequate organ function:&#xD;
&#xD;
        Absolute neutrophil (N) count ≥ 1500/mm3 ou ≥ 1,5.10^9/L Platelets ≥ 100 000 / mm3&#xD;
        Haemoglobin ≥ 9 g/dL Creatinine clearance ≥ 30 mL/min (by the MDRD formula) Total bilirubin&#xD;
        ≤ 1.5 x ULN (upper limit of the normal range) AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN OR AST&#xD;
        and ALT ≤ 5 x ULN if liver abnormalities due to liver metastases AST = aspartate&#xD;
        aminotransferase ALT = alanine aminotransferase&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          -  Patients who have never received chemotherapy with a platinum (cisplatin or&#xD;
             carboplatin)&#xD;
&#xD;
          -  Patients who have received more than one previous line of systemic treatment for&#xD;
             penile cancer unless in case of more than 12 months delay between the end of prior&#xD;
             treatment and the start of platinum containing polychemotherapy required.&#xD;
&#xD;
          -  Patients whose disease has progressed according to RECIST v1.1 criteria after 1st line&#xD;
             chemotherapy for penile cancer. The cancer must not be in the progression phase at&#xD;
             inclusion&#xD;
&#xD;
          -  Past history of immunotherapy treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1,&#xD;
             anti-PD-L2, anti-CD137, or an anti- CTLA-4 antibody (including ipilimumab) or any&#xD;
             other antibody or medicinal products specifically targeting anti-cancer immunotherapy&#xD;
&#xD;
          -  Major surgery within 4 weeks or major radiotherapy within 2 weeks prior to starting&#xD;
             avelumab. Previous palliative radiotherapy (≤ 10 fractions) for metastatic lesions is&#xD;
             permitted, provided that this has been completed at least 48 hours prior to starting&#xD;
             avelumab&#xD;
&#xD;
          -  Patients with a past history of known central nervous system metastases, meningeal&#xD;
             carcinomatosis or spinal compression&#xD;
&#xD;
          -  Existence of a past history of cancer within 3 years prior to inclusion into the study&#xD;
             (excluding cured localised cancer such as non-melanomatous skin cancers, superficial&#xD;
             bladder cancers and localised prostate cancer with undetectable PSA)&#xD;
&#xD;
          -  Active autoimmune disease, which may deteriorate following administration of an&#xD;
             immunostimulatory agent. Patients suffering from type I diabetes, vitiligo, psoriasis&#xD;
             or hypo- or hyperthyroidism not requiring immunosuppressant treatment are eligible&#xD;
&#xD;
          -  Patients with uncontrolled adrenal failure&#xD;
&#xD;
          -  Any of the following events in the 3 months prior to inclusion: myocardial infarction,&#xD;
             severe/unstable angina, coronary/periphery artery bypass, symptomatic congestive heart&#xD;
             failure, cerebrovascular accident, transient ischaemic attack.&#xD;
&#xD;
          -  Pulmonary embolism or deep vein thrombosis within 3 months prior to inclusion (unless&#xD;
             if stable, asymptomatic and treated with a low molecular heparin for at least 10 days&#xD;
             prior to starting the avelumab)&#xD;
&#xD;
          -  Active infection requiring systemic treatment&#xD;
&#xD;
          -  Current treatment with an immunosuppressant medicinal product or treatment within 7&#xD;
             days prior to inclusion, EXCEPT:&#xD;
&#xD;
        a - Intra-nasal, inhaled or local steroids or local steroid injections (such as&#xD;
        intra-articular injections) b - Systemic corticosteroids at physiological doses of ≤ 10&#xD;
        mg/day of prednisone or equivalent c - Steroids as premedication for hypersensitivity&#xD;
        reactions (such as CT scan premedication).&#xD;
&#xD;
          -  Diagnosis of human immunodeficiency virus (HIV) infection or disease related to the&#xD;
             acquired immunodeficiency syndrome (AIDS). In patients who are seropositive for HIV&#xD;
             but have a disease deemed to be controlled on anti-viral therapy from the opinion of&#xD;
             the patient's HIV contact doctor: inclusion is still possible if the CD4 count is ≥&#xD;
             300/mm3&#xD;
&#xD;
          -  Previous organ transplant including stem cell allotransplantation&#xD;
&#xD;
          -  Any screening test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating&#xD;
             active infection&#xD;
&#xD;
          -  Vaccination within 4 weeks prior to first administration of avelumab and throughout&#xD;
             the period of the study, except with inactivated vaccines (such as, inactivated&#xD;
             influenza vaccines).&#xD;
&#xD;
          -  Men of childbearing age who do not wish or cannot use 2 methods of highly effective&#xD;
             contraception (oral contraceptives, contraceptive injections, intra-uterine devices,&#xD;
             dual barrier method or contraceptive patches) as described in the protocol throughout&#xD;
             the study and for at least 60 days after the last dose of avelumab&#xD;
&#xD;
          -  Other severe acute or chronic medical conditions including immune colitis,&#xD;
             inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric&#xD;
             conditions including recent (within the past year) or active suicidal ideation or&#xD;
             behavior; or laboratory abnormalities that may increase the risk associated with study&#xD;
             participation or study treatment administration or may interfere with the&#xD;
             interpretation of study results and, in the judgment of the investigator, would make&#xD;
             the patient inappropriate for entry into this study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Elise Robert</last_name>
    <phone>0033381219086</phone>
    <email>e1robert@chu-besancon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Diane Berthod</last_name>
    <phone>0033370632403</phone>
    <email>dberthod@chu-besancon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Antoine THIERY VUILLEMIN</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine THIERY-VUILLEMIN, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>Penile Cancer</keyword>
  <keyword>Penile Squamous Cell Carcinoma</keyword>
  <keyword>Avelumab</keyword>
  <keyword>maintenance</keyword>
  <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>
    <mesh_term>Penile Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</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/NCT03774901
org study id: P/2017/337
secondary id: 2018-001427-38
nct id: NCT03774901
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients with unresectable locally advanced or metastatic squamous cell penile carcinoma
      (SPC) who are in response or with stable disease after first line platinum containing
      polychemotherapy who meet the inclusion/exclusion criteria will be offered to take part in
      the study.

      The patients may be pre-screened at the time of the 1st line chemotherapy.

      In order for patients to be enrolled, the investigator must have carried out a radiological
      assessment of the disease during first line systemic treatment (a maximum of between 3 and 6
      cycles): the cancer must be controlled. Patients with disease progression cannot be included
      in the PULSE study as this is a maintenance study.

      After inclusion, Avelumab will be administered at a dose of 10 mg/kg, at a frequency of once
      every 2 weeks with appropriate supportive care.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS (progression-free survival)
time frame: 24 months
description: To estimate progression-free survival in patients included in this study
measure: OS (overall survival)
time frame: 32 months
description: To estimate overall survival in patients included in this study
measure: MDT (median duration of treatment)
time frame: 24 months
description: To estimate the median duration of avelumab treatment calculated from avelumab initiation in patients included in this study
measure: QOL (quality of life) assessed by EORTC QLQ-C30
time frame: 24 months
description: To assess health-related quality of life since avelumab is started in patients included in this study
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
time frame: 24 months
description: To assess safety profile after avelumab initiation
arm group label: avelumab maintenance
arm group type: Experimental
description: Avelumab will be administered at a dose of 10 mg/kg every 2 weeks with appropriate supportive care
intervention type: Drug
intervention name: Avelumab
description: intravenous 10 mg/kg every 2 weeks
arm group label: avelumab maintenance
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elise Robert
phone: 0033381219086
email: e1robert@chu-besancon.fr
last name: Diane Berthod
phone: 0033370632403
email: dberthod@chu-besancon.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Penile Neoplasms
mesh term: Avelumab
sharing ipd: Undecided