<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/NCT01700049</url>
  </required_header>
  <id_info>
    <org_study_id>ML28485</org_study_id>
    <secondary_id>22355</secondary_id>
    <nct_id>NCT01700049</nct_id>
  </id_info>
  <brief_title>Study Evaluating the Efficacy of Oral Vismodegib in Various Histologic Subtypes</brief_title>
  <official_title>ML28485:Phase 2B Single-site,Open-label,Nonrandomized Study Evaluating Efficacy of Oral Vismodegib in Various Histologic Subtypes (Infiltrative/Morpheaform,Nodular and Superficial)of High Risk and/or Locally Advanced Basal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the safety and effectiveness of oral vismodegib&#xD;
      therapy in the treatment of different 'histologic subtypes' of basal cell skin cancer (BCC).&#xD;
      The term 'histologic subtype' refers to how the cells and tumor tissue looks under the&#xD;
      microscope. Three different 'histologic subtypes' of basal cell skin cancer&#xD;
      (infiltrative/morpheaform, nodular and superficial) will be examined in this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to investigate the safety and effectiveness of oral vismodegib&#xD;
      therapy in the treatment of different 'histologic subtypes' of basal cell skin cancer (BCC).&#xD;
      The term 'histologic subtype' refers to how the cells and tumor tissue looks under the&#xD;
      microscope. Three different 'histologic subtypes' of basal cell skin cancer&#xD;
      (infiltrative/morpheaform, nodular and superficial) will be examined in this study. Each&#xD;
      subtype has a characteristic look under the microscope, which is related to how the tumor&#xD;
      will behave and grow.&#xD;
&#xD;
      ERIVEDGE (oral vismodegib capsule) has been approved for use in the United States for&#xD;
      treatment of metastatic BCC tumors (mBCC), tumors that have spread further into the skin,&#xD;
      bones or other tissues, or spread to other parts of the body and locally advanced basal cell&#xD;
      skin cancer (laBCC), cancers that have come back after surgery or that the healthcare&#xD;
      provider thinks cannot be treated with surgery or radiation. It works by blocking the signal,&#xD;
      called Hedgehog, which basal cell skin cancer cells need to grow. It has been given to about&#xD;
      800 people during clinical trials.&#xD;
&#xD;
      Data from previous studies is mostly based on a subtype of BCC made up of little round&#xD;
      collections of cancer cells, called &quot;Nodular&quot;. There is almost no data on the use of&#xD;
      vismodegib in other subtypes of BCC that that tend to extend deep into the skin&#xD;
      (&quot;Infiltrative&quot; subtype), or spread widely near the surface of the skin (&quot;Superficial&quot;&#xD;
      subtype).&#xD;
&#xD;
      A total of 36 subjects will be enrolled in the study. All study participants will receive&#xD;
      oral vismodegib treatment.&#xD;
&#xD;
      At the Week 12 visit, skin biopsies will be performed to give the investigators more&#xD;
      information on how the tumor is responding to vismodegib. If there is no evidence of tumor on&#xD;
      the biopsy, the subject will be eligible to end treatment early and enter the Observation&#xD;
      period. During this time the subject will be followed clinically every 3 months for up to 1&#xD;
      year.&#xD;
&#xD;
      For all other subjects, if any evidence of tumor is seen on biopsy at week 12, the subject&#xD;
      will continue treatment for the full 24 weeks. At week 24 visit, skin biopsies will be&#xD;
      performed again to see if there is any tumor left. If there is no evidence of tumor on the&#xD;
      biopsy, the subject will be eligible to end treatment early and enter the Observation period.&#xD;
      If there is tumor left, the subject will be referred for surgery or other standard of care&#xD;
      treatment to remove the tumor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2013</start_date>
  <completion_date type="Actual">July 3, 2018</completion_date>
  <primary_completion_date type="Actual">July 3, 2017</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>Efficacy of Vismodegib</measure>
    <time_frame>Week 24</time_frame>
    <description>The efficacy of vismodegib was defined as the number of tumor biopsies with positive pathology after 24 weeks. Subjects had one target lesion and up to 3 additional non-target lesions. A cumulative total of 65 tumors was measured after 24 weeks of treatment. Histopathological subtypes were categorized primarily as infiltrative, nodular and superficial.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of Vismodegib</measure>
    <time_frame>Up to 18 months</time_frame>
    <description>The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Onset of Efficacy of Vismodegib</measure>
    <time_frame>Up to week 24</time_frame>
    <description>Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Basal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Open Label oral vismodegib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma (BCC). A total of 36 subjects with infiltrative/morpheaform, nodular, or superficial BCC will be enrolled in the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vismodegib (150 mg PO daily)</intervention_name>
    <description>Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
    <arm_group_label>Open Label oral vismodegib</arm_group_label>
    <other_name>Brand name: Erivedge</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A signed and data informed consent&#xD;
&#xD;
          2. Willing to comply with scheduled visits, treatment plan, laboratory tests, and other&#xD;
             study procedures&#xD;
&#xD;
          3. 18 years of age or older at time of informed consent&#xD;
&#xD;
          4. Have one or more clinically suspicious lesions for BCC at Pre-Study screening Visit&#xD;
             that has:&#xD;
&#xD;
               1. a diameter ≥ 6 mm if located on the &quot;mask areas&quot; of face (central face, eyelids,&#xD;
                  eyebrows, periorbital,nose,lips,chin,mandible,preauricular and postauricular&#xD;
                  skin/sulci,temple,ear),genitalia,hands,or feet&#xD;
&#xD;
               2. a diameter ≥ 10 mm if located on cheeks,forehead,scalp,or neck&#xD;
&#xD;
               3. a diameter ≥ 20 mm if located on trunk and extremities&#xD;
&#xD;
                  or has a lesion suspicious for locally advanced BCC defined as a lesion that:&#xD;
&#xD;
               4. is ≥ 10 mm,&#xD;
&#xD;
               5. has recurred following surgery or surgical resection would result in substantial&#xD;
                  deformity, and&#xD;
&#xD;
               6. has been deemed not appropriate for radiation.&#xD;
&#xD;
          5. Have a histologically-confirmed BCC prior to first dose of study drug&#xD;
&#xD;
          6. Have an Eastern Cooperative Oncology Group performance status of 2 or less at Baseline&#xD;
&#xD;
          7. Female of reproductive potential must use 2 effective methods to avoid pregnancy&#xD;
             during therapy and for 7 months after completing therapy&#xD;
&#xD;
          8. Male patients must use effective measures to avoid pregnancy in their partner at all&#xD;
             times during treatment and for 2 months after the last dose&#xD;
&#xD;
          9. Agree not to donate blood or blood products during the study and for 7 months after&#xD;
             the last dose&#xD;
&#xD;
         10. Subjects with Basal Cell Nevus Syndrome are eligible for enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant, lactating, or planning pregnancy while in the study&#xD;
&#xD;
          2. History of prior treatment with vismodegib or any Hh Pathway Inhibitor&#xD;
&#xD;
          3. Evidence of clinically significant and unstable diseases or conditions; Subjects with&#xD;
             clinically stable chronic medical conditions will be allowed to enter the study&#xD;
&#xD;
          4. Any dermatological disease at treatment site that the investigator thinks may be&#xD;
             exacerbated by treatment with vismodegib or cause difficulty with examination&#xD;
&#xD;
          5. The target lesion identified at Pre-study Screening visit has been determined to be&#xD;
             mBCC by radiological assessment prior to first dose of study drug&#xD;
&#xD;
          6. Inability or unwillingness to swallow capsules&#xD;
&#xD;
          7. History of infection requiring hospitalization, IV antimicrobial therapy, or is&#xD;
             otherwise judged to be clinically significant by the investigator within 4 wks prior&#xD;
             to first dose of study drug&#xD;
&#xD;
          8. History of infection requiring antimicrobial therapy within 2 wks prior to first dose&#xD;
             of study drug&#xD;
&#xD;
          9. History of alcohol or substance abuse, unless in full remission for greater than 6&#xD;
             months prior to first dose of study drug&#xD;
&#xD;
         10. Known to be infected with human immunodeficiency virus, hepatitis B or hepatitis C&#xD;
             viruses&#xD;
&#xD;
         11. Participation in other study using an investigational or experimental therapy or&#xD;
             procedure within 4 weeks or 5 half-lives (whichever is longer) before the study begins&#xD;
             and/or during study participation&#xD;
&#xD;
         12. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results in the judgment of the investigator&#xD;
&#xD;
         13. Subjects who are study site staff members or who are Sponsor employees directly&#xD;
             involved in the conduct of the trial&#xD;
&#xD;
         14. A subject who, in the opinion of the investigator or sponsor, will be uncooperative or&#xD;
             unable to comply with study procedures&#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>Scott Fosko, MD</last_name>
    <role>Study Director</role>
    <affiliation>fosko.scott@mayo.edu</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saint Louis University Department of Dermatology</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <reference>
    <citation>Lorusso PM, Jimeno A, Dy G, Adjei A, Berlin J, Leichman L, Low JA, Colburn D, Chang I, Cheeti S, Jin JY, Graham RA. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2011 Sep 1;17(17):5774-82. doi: 10.1158/1078-0432.CCR-11-0972. Epub 2011 Jul 13.</citation>
    <PMID>21753154</PMID>
  </reference>
  <reference>
    <citation>Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):389-402. doi: 10.1023/B:CANC.0000031775.04618.30.</citation>
    <PMID>15197337</PMID>
  </reference>
  <reference>
    <citation>Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9. doi: 10.1056/NEJMoa1113713.</citation>
    <PMID>22670903</PMID>
  </reference>
  <reference>
    <citation>Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH Jr. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012 Jun 7;366(23):2180-8. doi: 10.1056/NEJMoa1113538.</citation>
    <PMID>22670904</PMID>
  </reference>
  <reference>
    <citation>Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.</citation>
    <PMID>19726763</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>March 21, 2019</results_first_submitted>
  <results_first_submitted_qc>May 1, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 23, 2019</results_first_posted>
  <last_update_submitted>May 1, 2019</last_update_submitted>
  <last_update_submitted_qc>May 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Scott W. Fosko</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>advanced BCC</keyword>
  <keyword>high risk</keyword>
  <keyword>locally advanced</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/49/NCT01700049/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Open Label Oral Vismodegib</title>
          <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma (BCC).&#xD;
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Open Label Oral Vismodegib</title>
          <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma.&#xD;
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.5" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy of Vismodegib</title>
        <description>The efficacy of vismodegib was defined as the number of tumor biopsies with positive pathology after 24 weeks. Subjects had one target lesion and up to 3 additional non-target lesions. A cumulative total of 65 tumors was measured after 24 weeks of treatment. Histopathological subtypes were categorized primarily as infiltrative, nodular and superficial.</description>
        <time_frame>Week 24</time_frame>
        <population>A total of 65 tumors were categorized into histopathologic subtype where 24 of 65 were infiltrative, 29 of 65 were nodular, 10 of 65 were superficial and 2 out of 65 were keratotic.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Oral Vismodegib</title>
            <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma.&#xD;
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Vismodegib</title>
          <description>The efficacy of vismodegib was defined as the number of tumor biopsies with positive pathology after 24 weeks. Subjects had one target lesion and up to 3 additional non-target lesions. A cumulative total of 65 tumors was measured after 24 weeks of treatment. Histopathological subtypes were categorized primarily as infiltrative, nodular and superficial.</description>
          <population>A total of 65 tumors were categorized into histopathologic subtype where 24 of 65 were infiltrative, 29 of 65 were nodular, 10 of 65 were superficial and 2 out of 65 were keratotic.</population>
          <units>tumors</units>
          <param>Count of Units</param>
          <units_analyzed>tumors</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>tumors</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Infiltrative</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>tumors</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nodular</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>tumors</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Superficial</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>tumors</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Keratotic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>tumors</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety of Vismodegib</title>
        <description>The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death.</description>
        <time_frame>Up to 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label Oral Vismodegib</title>
            <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma. vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of Vismodegib</title>
          <description>The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death.</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Onset of Efficacy of Vismodegib</title>
        <description>Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area.</description>
        <time_frame>Up to week 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label Oral Vismodegib</title>
            <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma.&#xD;
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
          </group>
        </group_list>
        <measure>
          <title>Onset of Efficacy of Vismodegib</title>
          <description>Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area.</description>
          <units>tumors</units>
          <param>Count of Units</param>
          <units_analyzed>tumors</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>tumors</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The study period during which all Adverse Events (AE) and Serious Adverse Events (SAE) must be reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open Label Oral Vismodegib</title>
          <description>This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma.&#xD;
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Congestive Heart Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastrointestinal bleed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Exacerbation of low back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neurogenic claudication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperlipidemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated blood pressure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurry vision</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia/Loss of Taste</sub_title>
                <counts group_id="E1" events="24" subjects_affected="24" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abnormal hair growth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Scalp tenderness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Falls</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Decrease in eyelashes/eyebrows</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Stunted nail growth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tooth pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Visual hallucinations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Burning sensation of tongue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Halitosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lower extremity edema/intermittent swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Viral syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Salivary gland infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite/anorexia/weight loss</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="23" subjects_affected="23" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Joint aches</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle aches</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Maxillary fibrous cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sprain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Orthostatic tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal bleeding</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Itching/pruritus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Comedones</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Actinic keratosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Biopsy site inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rosacea flare</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Eyelid reconstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral arterial disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Scott Fosko</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>904-953-2303</phone>
      <email>fosko.scott@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01700049
org study id: ML28485
secondary id: 22355
nct id: NCT01700049
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to investigate the safety and effectiveness of oral vismodegib
      therapy in the treatment of different 'histologic subtypes' of basal cell skin cancer (BCC).
      The term 'histologic subtype' refers to how the cells and tumor tissue looks under the
      microscope. Three different 'histologic subtypes' of basal cell skin cancer
      (infiltrative/morpheaform, nodular and superficial) will be examined in this study.
The purpose of this study is to investigate the safety and effectiveness of oral vismodegib
      therapy in the treatment of different 'histologic subtypes' of basal cell skin cancer (BCC).
      The term 'histologic subtype' refers to how the cells and tumor tissue looks under the
      microscope. Three different 'histologic subtypes' of basal cell skin cancer
      (infiltrative/morpheaform, nodular and superficial) will be examined in this study. Each
      subtype has a characteristic look under the microscope, which is related to how the tumor
      will behave and grow.

      ERIVEDGE (oral vismodegib capsule) has been approved for use in the United States for
      treatment of metastatic BCC tumors (mBCC), tumors that have spread further into the skin,
      bones or other tissues, or spread to other parts of the body and locally advanced basal cell
      skin cancer (laBCC), cancers that have come back after surgery or that the healthcare
      provider thinks cannot be treated with surgery or radiation. It works by blocking the signal,
      called Hedgehog, which basal cell skin cancer cells need to grow. It has been given to about
      800 people during clinical trials.

      Data from previous studies is mostly based on a subtype of BCC made up of little round
      collections of cancer cells, called "Nodular". There is almost no data on the use of
      vismodegib in other subtypes of BCC that that tend to extend deep into the skin
      ("Infiltrative" subtype), or spread widely near the surface of the skin ("Superficial"
      subtype).

      A total of 36 subjects will be enrolled in the study. All study participants will receive
      oral vismodegib treatment.

      At the Week 12 visit, skin biopsies will be performed to give the investigators more
      information on how the tumor is responding to vismodegib. If there is no evidence of tumor on
      the biopsy, the subject will be eligible to end treatment early and enter the Observation
      period. During this time the subject will be followed clinically every 3 months for up to 1
      year.

      For all other subjects, if any evidence of tumor is seen on biopsy at week 12, the subject
      will continue treatment for the full 24 weeks. At week 24 visit, skin biopsies will be
      performed again to see if there is any tumor left. If there is no evidence of tumor on the
      biopsy, the subject will be eligible to end treatment early and enter the Observation period.
      If there is tumor left, the subject will be referred for surgery or other standard of care
      treatment to remove the tumor.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy of Vismodegib
time frame: Week 24
description: The efficacy of vismodegib was defined as the number of tumor biopsies with positive pathology after 24 weeks. Subjects had one target lesion and up to 3 additional non-target lesions. A cumulative total of 65 tumors was measured after 24 weeks of treatment. Histopathological subtypes were categorized primarily as infiltrative, nodular and superficial.
measure: Safety of Vismodegib
time frame: Up to 18 months
description: The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death.
measure: Onset of Efficacy of Vismodegib
time frame: Up to week 24
description: Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area.
arm group label: Open Label oral vismodegib
arm group type: Experimental
description: This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma (BCC). A total of 36 subjects with infiltrative/morpheaform, nodular, or superficial BCC will be enrolled in the study.
intervention type: Drug
intervention name: vismodegib (150 mg PO daily)
description: Biopsies will be performed on all participants at baseline, week 12 and week 24.
arm group label: Open Label oral vismodegib
other name: Brand name: Erivedge
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott Fosko, MD
role: Study Director
affiliation: fosko.scott@mayo.edu
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
citation: Lorusso PM, Jimeno A, Dy G, Adjei A, Berlin J, Leichman L, Low JA, Colburn D, Chang I, Cheeti S, Jin JY, Graham RA. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2011 Sep 1;17(17):5774-82. doi: 10.1158/1078-0432.CCR-11-0972. Epub 2011 Jul 13.
PMID: 21753154
citation: Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):389-402. doi: 10.1023/B:CANC.0000031775.04618.30.
PMID: 15197337
citation: Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9. doi: 10.1056/NEJMoa1113713.
PMID: 22670903
citation: Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH Jr. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012 Jun 7;366(23):2180-8. doi: 10.1056/NEJMoa1113538.
PMID: 22670904
citation: Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.
PMID: 19726763
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Scott W. Fosko
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Basal Cell
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 