<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/NCT01728233</url>
  </required_header>
  <id_info>
    <org_study_id>INT110/12</org_study_id>
    <nct_id>NCT01728233</nct_id>
  </id_info>
  <brief_title>Dacomitinib (PF-00299804) in Advanced/Metastatic Squamous Cell Carcinoma of the Penis</brief_title>
  <acronym>HER-Uro01</acronym>
  <official_title>Phase II Study of the Pan-HER Inhibitor Dacomitinib (PF-00299804) for Patients With Locally Advanced or Metastatic Squamous Cell Carcinoma of the Penis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Penile squamous cell carcinoma (SCC) is a very rare disease and prognosis depends primarily&#xD;
      on regional lymph-node involvement. Despite the fact that cure can be obtained in patients&#xD;
      with low metastatic load (pN1) by monotherapy, combination therapy is required for more&#xD;
      advanced cases. Medical treatment options only for advanced or metastatic penile SCC are not&#xD;
      very effective so far and the few chances for cure are solely dependent on multimodality&#xD;
      treatment, either with surgery or radiation. Based on the observation that the epidermal&#xD;
      growth factor receptor (EGFR) is almost invariably expressed in penile SCC and assuming&#xD;
      similarities to the SCC of head and neck district, anti-EGFR targeted monotherapy has been&#xD;
      investigated with promising early results at Istituto Tumori Milan and University of Texas MD&#xD;
      Andreson Cancer Center. These premises lend support to the use of the pan-HER inhibitor&#xD;
      dacomitinib for advanced or metastatic penile SCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2013</start_date>
  <completion_date type="Actual">September 21, 2018</completion_date>
  <primary_completion_date type="Actual">September 21, 2018</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>The primary outcome measure will be the assessment of response-rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.</measure>
    <time_frame>2-months</time_frame>
    <description>RR (%) = complete response (CR) + partial response (PR), where CR is the disappearance of all target lesions (any pathological lymph-nodes must have reduction in short axis to &lt; 10 mm) and PR indicates at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the safety and tolerability of the study drug. Incidence, nature and severity of treatment-related adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.</measure>
    <time_frame>2-months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic complete response (pCR) rate for patients undergoing surgery in the treatment time course.</measure>
    <time_frame>2-months or longer.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival.</measure>
    <time_frame>2-months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>6-months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language.</measure>
    <time_frame>2-months.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Penile Neoplasms</condition>
  <condition>Carcinoma, Squamous Cell</condition>
  <arm_group>
    <arm_group_label>Dacomitinib (PF-00299804)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PF-299804 will be administered orally at a dose of 45 mg/day continuously until surgery, evidence of disease progression or onset of unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dacomitinib</intervention_name>
    <description>PF-299804 will be administered orally at a dose of 45 mg/day continuously until surgery, evidence of disease progression or onset of unacceptable toxicity.</description>
    <arm_group_label>Dacomitinib (PF-00299804)</arm_group_label>
    <other_name>PF-00299804</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must provide written informed consent&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of at least 1&#xD;
&#xD;
          -  Cytologically or histologically proven diagnosis of SCC of the penis&#xD;
&#xD;
          -  Uni- or bidimensionally measurable disease as defined by RECIST v1.1 criteria&#xD;
&#xD;
          -  Clinical stage N2-3 and/or M1 (TNM 2002)&#xD;
&#xD;
          -  Locoregional relapse after prior major surgery/ies (either single or multiple)&#xD;
&#xD;
          -  No prior systemic therapy except for the administration of&#xD;
             vincristine-bleomycin-methotrexate (VBM) chemotherapy for superficial disease if&#xD;
             administered at least 6 months prior to study enrollment&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Central nervous system (CNS) metastases or leptomeningeal carcinomatosis&#xD;
&#xD;
          -  History of active serious cardiovascular, cerebrovascular, pulmonary co-morbidities&#xD;
&#xD;
          -  Previous or concurrent cancer that is distinct in primary site or histology from the&#xD;
             cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal&#xD;
             cell carcinoma or any cancer curatively treated &gt; 5 years prior to study entry.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrea Necchi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roberto Salvioni, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <last_update_submitted>May 12, 2021</last_update_submitted>
  <last_update_submitted_qc>May 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</investigator_affiliation>
    <investigator_full_name>Andrea Necchi</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Molecular Targeted Therapy</keyword>
  <keyword>Neoadjuvant therapy</keyword>
  <keyword>Dacomitinib</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>
  <!-- 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/NCT01728233
org study id: INT110/12
nct id: NCT01728233
lead sponsor: 
collaborator: 
has dmc: Yes
Penile squamous cell carcinoma (SCC) is a very rare disease and prognosis depends primarily
      on regional lymph-node involvement. Despite the fact that cure can be obtained in patients
      with low metastatic load (pN1) by monotherapy, combination therapy is required for more
      advanced cases. Medical treatment options only for advanced or metastatic penile SCC are not
      very effective so far and the few chances for cure are solely dependent on multimodality
      treatment, either with surgery or radiation. Based on the observation that the epidermal
      growth factor receptor (EGFR) is almost invariably expressed in penile SCC and assuming
      similarities to the SCC of head and neck district, anti-EGFR targeted monotherapy has been
      investigated with promising early results at Istituto Tumori Milan and University of Texas MD
      Andreson Cancer Center. These premises lend support to the use of the pan-HER inhibitor
      dacomitinib for advanced or metastatic penile SCC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The primary outcome measure will be the assessment of response-rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
time frame: 2-months
description: RR (%) = complete response (CR) + partial response (PR), where CR is the disappearance of all target lesions (any pathological lymph-nodes must have reduction in short axis to < 10 mm) and PR indicates at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
measure: To assess the safety and tolerability of the study drug. Incidence, nature and severity of treatment-related adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
time frame: 2-months
measure: Pathologic complete response (pCR) rate for patients undergoing surgery in the treatment time course.
time frame: 2-months or longer.
measure: Progression-free survival.
time frame: 2-months.
measure: Overall Survival
time frame: 6-months
measure: Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language.
time frame: 2-months.
arm group label: Dacomitinib (PF-00299804)
arm group type: Experimental
description: PF-299804 will be administered orally at a dose of 45 mg/day continuously until surgery, evidence of disease progression or onset of unacceptable toxicity.
intervention type: Drug
intervention name: Dacomitinib
description: PF-299804 will be administered orally at a dose of 45 mg/day continuously until surgery, evidence of disease progression or onset of unacceptable toxicity.
arm group label: Dacomitinib (PF-00299804)
other name: PF-00299804
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Andrea Necchi, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
last name: Roberto Salvioni, MD
role: Study Chair
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
investigator full name: Andrea Necchi
investigator title: MD
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Penile Neoplasms