<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/NCT03035188</url>
  </required_header>
  <id_info>
    <org_study_id>ADO-EP02 (ML29328)</org_study_id>
    <nct_id>NCT03035188</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Vismodegib in Patients With Large and/or Recurrent Resectable Basal Cell Carcinoma</brief_title>
  <acronym>NICCI</acronym>
  <official_title>A Phase II, Single-armed, Multicenter Trial of Neoadjuvant Vismodegib in Patients With Large and/or Recurrent Resectable Basal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SRH Wald-Klinikum Gera GmbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SRH Wald-Klinikum Gera GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study patients with resectable basal cell carcinoma (BCC) who usually undergo surgery&#xD;
      without prior anticancer treatment will be treated with antitumor medication. But since BCC&#xD;
      is mainly localized in clearly visible regions of the body, as e.g. the face, there is also a&#xD;
      need to reduce scars as a consequence of surgery which will be accomplished by neoadjuvant&#xD;
      therapy.&#xD;
&#xD;
      The used medication - vismodegib - displays controllable adverse events and shows a good&#xD;
      efficacy for reduction of BCC lesions. It is expected that the neoadjuvant setting will lead&#xD;
      to minor surgical intervention thus minimising surgical risks and scars for the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with resectable BCC will receive neoadjuvant vismodegib therapy for a time period of&#xD;
      12 weeks which applies to the routine use of vismodegib. This period is chosen because within&#xD;
      this time side effects are acceptable and response is expected. Tumor examination will be&#xD;
      performed monthly to expeditiously identify patients with progressive disease. This will be&#xD;
      done by non-invasive imaging techniques thus a further objective of this study is the testing&#xD;
      of diagnostic suitability of non-invasive methodology for the evaluation of response status&#xD;
      of the patients.&#xD;
&#xD;
      Patients in this clinical trial will be treated with an effective medication which is&#xD;
      approved for the therapy of metastatic and locally advanced BCC for a time having been shown&#xD;
      to be effective in neoadjuvant setting The same dose as approved for the advanced BCC disease&#xD;
      is used, therefore it can be expected that the side effects will be predictable. Furthermore&#xD;
      there are no hints in literature that the efficacy of the used medication may be decreased in&#xD;
      patients with resectable BCC.&#xD;
&#xD;
      Since the study patients are less sick than those for whom treatment with vismodegib is&#xD;
      approved, surgery would be their therapy according to guideline. Thus the risk of vismodegib&#xD;
      treatment has to be judged against the greater surgical risk if BCC will be operated directly&#xD;
      without prior reduction of tumor lesion. A benefit for the great majority of the patients&#xD;
      will be that smaller lesions result in minor scars and better cosmetically outcome of&#xD;
      surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">January 2021</completion_date>
  <primary_completion_date type="Actual">January 2020</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>Disease control rate (DCR) defined as complete response (CR), partial response (PR), or stable disease (SD) after 12 weeks of treatment with vismodegib</measure>
    <time_frame>12 weeks</time_frame>
    <description>Rate of patients with CR, PR and SD</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective and relative (%) reduction of the involved skin surface after 12 weeks of treatment with vismodegib</measure>
    <time_frame>12 weeks</time_frame>
    <description>Percent change of the BCC area from baseline to end of study therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>DCR (CR, PR, or SD) after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting for different basal cell carcinoma histotypes (superficial, scleroderma, nodular, others)</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of overall response (DoR)</measure>
    <time_frame>12 months</time_frame>
    <description>Time from documented CR, PR or SD until progression of disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life in patients receiving vismodegib for neoadjuvant treatment of basal cell carcinoma as measured by the Skindex-16 questionnaire</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Diagnostic suitability of non-invasive imaging techniques (in vivo confocal laserscan-microscopy and/or optical coherence tomography for the evaluation of response status of patients receiving vismodegib in the neoadjuvant setting)</measure>
    <time_frame>12 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Basal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Vismodegib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Continuous once-daily oral dosing of vismodegib at a dosage of 150 mg per administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vismodegib</intervention_name>
    <description>1 capsule (150 mg vismodegib) taken once daily for a maximum of 12 weeks.</description>
    <arm_group_label>Vismodegib</arm_group_label>
    <other_name>Erivedge</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patient aged ≥ 18 years&#xD;
&#xD;
          2. Able to participate and willing to give written informed consent including consent for&#xD;
             photographs prior to performance of study-related procedures and to comply with the&#xD;
             study protocol.&#xD;
&#xD;
          3. Patients with at least 1 large (≥ 2 cm in diameter in head/neck region, ≥ 5 cm for&#xD;
             trunk/extremities) basal cell carcinoma (BCC), still resectable, but with increased&#xD;
             risk for cosmetic disfigurement or functional defects by assessment of the enrolling&#xD;
             physician. Patients with large (as defined above) recurrent basal cell carcinoma are&#xD;
             also eligible.&#xD;
&#xD;
          4. Patients must be naïve to treatment with vismodegib or other hedgehog pathway&#xD;
             inhibitors&#xD;
&#xD;
          5. Local histopathologic confirmation of BCC (3 mm punch biopsy)&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2&#xD;
&#xD;
          7. Consent to undergo mapping biopsies upon reaching complete response&#xD;
&#xD;
             Adequate hematologic and organ function, defined by the following laboratory results,&#xD;
             to be obtained within 7 days prior to registration and prior to first dose of study&#xD;
             drug treatment:&#xD;
&#xD;
               -  Absolute neutrophilic count &gt; 1,0 x 109/L&#xD;
&#xD;
               -  Platelet count ≥ 75 x 109/L&#xD;
&#xD;
               -  Hemoglobin ≥ 8,5 g/dL&#xD;
&#xD;
               -  Albumin ≥ 2.5 g/dL&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 x the upper limit of normal (ULN) or within 3 x ULN for patients&#xD;
&#xD;
               -  Aspartate-aminotransferase, Alanine-aminotransferase, and alkaline phosphatase ≤&#xD;
                  3 x ULN&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
          8. Female patients of childbearing potential must agree to always use 2 effective forms&#xD;
             of contraception including one highly effective method and a barrier method during&#xD;
             treatment with study medication and for 24 months after the final dose. Male patients&#xD;
             with partners of childbearing potential must always use a condom (with spermicide, if&#xD;
             available), even after a vasectomy, during treatment with study medication and for at&#xD;
             least 2 months after the final dose. Breast feeding is likewise not allowed for at&#xD;
             least 24 months after completion of study therapy.&#xD;
&#xD;
          9. Negative serum pregnancy test within 7 days prior to commencement of dosing in women&#xD;
             of childbearing potential (including pre-menopausal women with tubal ligation).&#xD;
&#xD;
         10. Absence of any psychological, familial, sociological, or geographical condition that&#xD;
             potentially hampers compliance with the study protocol and follow-up as defined by the&#xD;
             treatment discontinuation schedule.&#xD;
&#xD;
         11. Agreement not to donate blood or blood products during the study and for at least 24&#xD;
             months after discontinuation of vismodegib. Because vismodegib has been detected in&#xD;
             seminal fluid, in addition for men, agreement not donate sperm during the study or for&#xD;
             at least 2 months after discontinuation of therapy&#xD;
&#xD;
         12. Optional: Consent to undergo non-invasive imaging examinations by means of confocal&#xD;
             laserscan-microscopy (CLSM) and/or optical coherence tomography (OCT), during and&#xD;
             after end of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of prior treatment with vismodegib or any other hedgehog pathway inhibitor.&#xD;
&#xD;
          2. Radiotherapy that involved the field of the target lesion within 6 months prior to&#xD;
             registration. Only one radiotherapy of the target lesion performed &gt; 6 months prior to&#xD;
             registration is allowed. If a second radiotherapy in this field took place, patient&#xD;
             will be excluded.&#xD;
&#xD;
          3. Any metastatic BCC&#xD;
&#xD;
          4. BCC lesion that is considered to be inoperable (e.g. medical contraindication to&#xD;
             surgery, suspicion of bone infiltration)&#xD;
&#xD;
          5. Metatypic BCC&#xD;
&#xD;
          6. Known or suspected Gorlin-Goltz syndrome&#xD;
&#xD;
          7. Uncontrolled medical illness, including advanced malignancies (no activities of the&#xD;
             malignancies in the past 3 years), at the discretion of the Investigator&#xD;
&#xD;
          8. History of other disease, metabolic dysfunction, physical examination finding, or&#xD;
             clinical laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug or that might affect interpretation&#xD;
             of the results of the study or renders the patient at high risk for treatment&#xD;
             complications&#xD;
&#xD;
          9. History (within 6 months prior to registration) or current signs or symptoms of&#xD;
             severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary,&#xD;
             gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or&#xD;
             metabolic disturbances&#xD;
&#xD;
         10. Any medical or psychological illness or condition preventing adequate consent or&#xD;
             ability to comply with the protocol&#xD;
&#xD;
         11. Inability or unwillingness to swallow capsules&#xD;
&#xD;
         12. Inability or unwillingness to comply with study and follow-up procedures&#xD;
&#xD;
         13. Current severe, uncontrolled systemic disease&#xD;
&#xD;
         14. History of malabsorption or other conditions that would interfere with the absorption&#xD;
             of the orally applicated study drug&#xD;
&#xD;
         15. Pregnant, lactating, or breast feeding women&#xD;
&#xD;
         16. Patients with one of the following rare hereditary conditions: galactose intolerance,&#xD;
             primary hypolactasia, or glucose-galactose malabsorption&#xD;
&#xD;
         17. Participation in another clinical study within 28 days before registration or within a&#xD;
             time period of five elimination half-lives of the slowest eliminated previously used&#xD;
             study drug (whichever is the longest time period).&#xD;
&#xD;
         18. Known or suspected alcohol or drug abuse in the opinion of the investigator&#xD;
&#xD;
         19. Known hypersensitivity reaction to vismodegib or any of the other ingredients of this&#xD;
             medicine&#xD;
&#xD;
         20. Treatment with St John's wort (Hypericum perforatum)&#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>Martin Kaatz, PD Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>martin.kaatz@wkg.srh.de</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SRH Wald-Klinikum Gera GmbH</name>
      <address>
        <city>Gera</city>
        <state>Thuringia</state>
        <zip>07548</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Augsburg Süd</name>
      <address>
        <city>Augsburg</city>
        <zip>86179</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elbe Kliniken Stade - Buxtehude GmbH</name>
      <address>
        <city>Buxtehude</city>
        <zip>21614</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Klinikum Erfurt</name>
      <address>
        <city>Erfurt</city>
        <zip>99089</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Münster</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fachklinik Hornheide</name>
      <address>
        <city>Münster</city>
        <zip>48157</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Nürnberg Nord</name>
      <address>
        <city>Nürnberg</city>
        <zip>90419</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harzklinikum Dorothea Christiane Erxleben GmbH</name>
      <address>
        <city>Quedlinburg</city>
        <zip>06484</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 26, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>February 10, 2022</last_update_submitted>
  <last_update_submitted_qc>February 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>resectable</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Basal Cell</mesh_term>
  </condition_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/NCT03035188
org study id: ADO-EP02 (ML29328)
nct id: NCT03035188
lead sponsor: 
has dmc: No
In this study patients with resectable basal cell carcinoma (BCC) who usually undergo surgery
      without prior anticancer treatment will be treated with antitumor medication. But since BCC
      is mainly localized in clearly visible regions of the body, as e.g. the face, there is also a
      need to reduce scars as a consequence of surgery which will be accomplished by neoadjuvant
      therapy.

      The used medication - vismodegib - displays controllable adverse events and shows a good
      efficacy for reduction of BCC lesions. It is expected that the neoadjuvant setting will lead
      to minor surgical intervention thus minimising surgical risks and scars for the patients.
Patients with resectable BCC will receive neoadjuvant vismodegib therapy for a time period of
      12 weeks which applies to the routine use of vismodegib. This period is chosen because within
      this time side effects are acceptable and response is expected. Tumor examination will be
      performed monthly to expeditiously identify patients with progressive disease. This will be
      done by non-invasive imaging techniques thus a further objective of this study is the testing
      of diagnostic suitability of non-invasive methodology for the evaluation of response status
      of the patients.

      Patients in this clinical trial will be treated with an effective medication which is
      approved for the therapy of metastatic and locally advanced BCC for a time having been shown
      to be effective in neoadjuvant setting The same dose as approved for the advanced BCC disease
      is used, therefore it can be expected that the side effects will be predictable. Furthermore
      there are no hints in literature that the efficacy of the used medication may be decreased in
      patients with resectable BCC.

      Since the study patients are less sick than those for whom treatment with vismodegib is
      approved, surgery would be their therapy according to guideline. Thus the risk of vismodegib
      treatment has to be judged against the greater surgical risk if BCC will be operated directly
      without prior reduction of tumor lesion. A benefit for the great majority of the patients
      will be that smaller lesions result in minor scars and better cosmetically outcome of
      surgery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate (DCR) defined as complete response (CR), partial response (PR), or stable disease (SD) after 12 weeks of treatment with vismodegib
time frame: 12 weeks
description: Rate of patients with CR, PR and SD
measure: Objective and relative (%) reduction of the involved skin surface after 12 weeks of treatment with vismodegib
time frame: 12 weeks
description: Percent change of the BCC area from baseline to end of study therapy
measure: DCR (CR, PR, or SD) after 12 weeks of treatment with vismodegib in the neoadjuvant treatment setting for different basal cell carcinoma histotypes (superficial, scleroderma, nodular, others)
time frame: 12 weeks
measure: Duration of overall response (DoR)
time frame: 12 months
description: Time from documented CR, PR or SD until progression of disease
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 12 months
measure: Health-related quality of life in patients receiving vismodegib for neoadjuvant treatment of basal cell carcinoma as measured by the Skindex-16 questionnaire
time frame: 12 months
measure: Diagnostic suitability of non-invasive imaging techniques (in vivo confocal laserscan-microscopy and/or optical coherence tomography for the evaluation of response status of patients receiving vismodegib in the neoadjuvant setting)
time frame: 12 months
arm group label: Vismodegib
arm group type: Experimental
description: Continuous once-daily oral dosing of vismodegib at a dosage of 150 mg per administration
intervention type: Drug
intervention name: Vismodegib
description: 1 capsule (150 mg vismodegib) taken once daily for a maximum of 12 weeks.
arm group label: Vismodegib
other name: Erivedge
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin Kaatz, PD Dr.
role: Principal Investigator
affiliation: martin.kaatz@wkg.srh.de
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Basal Cell
sharing ipd: No