<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/NCT01692626</url>
  </required_header>
  <id_info>
    <org_study_id>WVU21011</org_study_id>
    <nct_id>NCT01692626</nct_id>
  </id_info>
  <brief_title>1% Topical Pimecrolimus Cream for the Treatment of the Rash Associated With ERBITUX</brief_title>
  <official_title>1% Topical Pimecrolimus Cream for the Prevention of Rash Associated With the Use of the EGFR Antagonist, Cetuximab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West Virginia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>West Virginia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      When cancer patients are treated with the drug cetuximab they very often develop a rash.&#xD;
      Usually it appears on their face and back and other parts of the body. The rash looks like&#xD;
      acne and is treated with skin creams or antibiotics most of the time. The rash can become&#xD;
      very painful and cause patients to stop using cetuximab to treat their cancer, even if&#xD;
      cetuximab was helping fight their cancer.&#xD;
&#xD;
      Cetuximab is known to be a good drug to help treat cancer. This study will help us learn&#xD;
      about the rash cetuximab causes so hopefully future patients can finish taking cetuximab for&#xD;
      their cancer. In this study the investigators will use a cream called pimecrolimus (Elidel)&#xD;
      to see if it will help prevent the rash or keep the rash from getting worse. The&#xD;
      investigators also want to see how the rash affects patients and their quality of life.&#xD;
&#xD;
      Participants will be in this study for about four weeks if their rash does not get worse.&#xD;
      They will need to apply the study cream and placebo two times daily and answer quality of&#xD;
      life questionnaires during this study. Participants will also be seen by a dermatologist and&#xD;
      have pictures taken of their rash.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adult patients who are being treated with cetuximab for a malignancy will be offered the&#xD;
      chance to take part in the study. Patients must provide written informed consent in order to&#xD;
      participate in the study (including consent to clinical photographs).&#xD;
&#xD;
      The area of skin to be treated with investigational cream will be the face. Baseline&#xD;
      photographs will be taken of the selected area of bilateral face.&#xD;
&#xD;
      Patients will be requested to apply a thin layer of the investigational cream twice daily to&#xD;
      one half of face at the same time they are started on cetuximab. Patients will be provided&#xD;
      with a placebo cream to apply to the other side of their face. Patients will be provided the&#xD;
      sufficient investigational cream free of charge for the duration of study. The study&#xD;
      coordinator will instruct the patient regarding which side of the face to apply the&#xD;
      investigational cream. This will be randomly assigned by the study coordinator based on a&#xD;
      randomization list generated by the biostatistics core and will only be known to the study&#xD;
      coordinator. The dermatologist and study investigators will remain blinded to the side to&#xD;
      which the investigational cream was applied. In this manner, patients will serve as their own&#xD;
      controls. Patients are free to use oral tetracyclines if recommended by their primary&#xD;
      oncologists. Patients on the trial, however, cannot use another rash treatment with the&#xD;
      exception of moisturizing agents.&#xD;
&#xD;
      Patients participating in the study will be instructed to apply a moisturizing cream, lotion,&#xD;
      or ointment of their choice to the face three times a day. Moisturizers should be applied to&#xD;
      the skin after, not before, the investigational cream application. Patients should not wet&#xD;
      the treated area of skin for one hour after applying investigational cream, otherwise it&#xD;
      could be washed off. The investigational cream should not be applied at or near the eyes.&#xD;
      Patients on study will be instructed to minimize sun exposure and to avoid exposure to&#xD;
      artificial sunlight. Patients should apply sunscreen to when exposed to sunlight, after the&#xD;
      investigational cream has been completely absorbed into the skin.&#xD;
&#xD;
      Patients will be given a copy of the Dermatology Life Quality Index (DLQI) questionnaire and&#xD;
      asked to complete it on all study visits. Patients will be given help to complete the&#xD;
      questionnaire if needed. The questionnaire and its interpretation are listed in the appendix.&#xD;
&#xD;
      Patients will be assessed at least every two weeks in person. These visits may coincide with&#xD;
      appointments with their primary oncologist for the treatment of their cancer. Patients will&#xD;
      be able to contact the study coordinator during the duration of the study. Patients will also&#xD;
      be requested to contact the study coordinator or investigators if the rash appears to worsen.&#xD;
&#xD;
      The rash will be assessed by their treating oncologist during each study visit. Their&#xD;
      treating oncologist will remain blinded to the side which the pimecrolimus cream was applied.&#xD;
      Clinical photographs of the rash will be taken.&#xD;
&#xD;
      When the rash appears predominantly on the side to which pimecrolimus was applied and the&#xD;
      rash appears to worsen in the first 24 hrs of application of pimecrolimus then the patient&#xD;
      will be considered allergic to pimecrolimus, and the treatment will be stopped.&#xD;
&#xD;
      The rash will be compared at both sides of the face documented using the National Cancer&#xD;
      Institute Common Terminology Criteria (NCI CTC) for acneiform rash. A papule and pustule&#xD;
      count will also be determined by the study dermatologist and documented from the clinical&#xD;
      photographs. Toxicity of topical pimecrolimus therapy will also be assessed as described in&#xD;
      the appendix. Toxicity assessment will be described using NCI CTC Version 4. Toxicities&#xD;
      observed will be defined as related (definitely, probably, possibly) or unrelated to topical&#xD;
      pimecrolimus treatment.&#xD;
&#xD;
      The total duration of the study will be for four weeks. After two weeks on topical&#xD;
      pimecrolimus patients will be requested to come to a study visit. This will be coordinated&#xD;
      with their usual oncologist visit if possible.&#xD;
&#xD;
      After the rash assessment at this visit, the treating oncologist and the patient will be&#xD;
      unblinded. If the intensity of the rash in the treated area is no worse than in the&#xD;
      corresponding untreated area on the opposite side using the NCI CTC version 4 scale for&#xD;
      acneiform rash, no severe toxicities occurred in the patient, and the patient finds the&#xD;
      pimecrolimus therapy tolerable, the patient will continue on study. At this study visit,&#xD;
      patients will also be given a copy of the DLQI and asked to complete it. Patients will be&#xD;
      given help to complete the questionnaire by the study coordinator if needed. The&#xD;
      questionnaire and its interpretation are listed in the appendix. Clinical photographs will be&#xD;
      taken.&#xD;
&#xD;
      Patients who experience a worsening of rash intensity by NCI CTC Version 4.0 at a treated&#xD;
      area, or who suffer a severe toxicity (grade 3 or 4) related to topical pimecrolimus, or who&#xD;
      find the topical pimecrolimus intolerable will discontinue use of pimecrolimus to that area&#xD;
      immediately and will come off study.&#xD;
&#xD;
      Patients who continue on study after the two week visit may apply a thin layer of 1% topical&#xD;
      pimecrolimus twice daily to both sides of face.&#xD;
&#xD;
      Patients who continue pimecrolimus therapy, beyond the initial rash assessment, will be&#xD;
      re-assessed after two weeks in the same manner as at the initial rash assessment. Patients&#xD;
      will remain on study for a maximum of 4 weeks since starting pimecrolimus therapy. At the 4&#xD;
      week study visit, patients will also be given a copy of the DLQI and asked to complete it.&#xD;
      Patients will be given help to complete the questionnaire by the study coordinator if needed.&#xD;
      The questionnaire and its interpretation is listed in the appendix&#xD;
&#xD;
      Patients who are considered to have benefited from pimecrolimus therapy at the 4 week visit&#xD;
      may choose to use commercially available pimecrolimus off protocol but will be advised that&#xD;
      the safety of topical pimecrolimus has not been established beyond one year of use, and that&#xD;
      insurance might not cover for treatment.&#xD;
&#xD;
      RATIONALE FOR STUDY DESIGN&#xD;
&#xD;
      There is no highly-effective treatment for epidermal growth factor receptor (EGFR)-inhibitor&#xD;
      induced rash. In this study patients will be offered 1% pimecrolimus cream, in addition to&#xD;
      other standard non-topical therapy such as oral tetracycline antibiotics and moisturizing&#xD;
      agents. Patients will apply 1% pimecrolimus cream to one side of the face at the time of&#xD;
      starting cetuximab. The opposite untreated side will serve as the control side. In this&#xD;
      controlled manner, if a decrease in papule and pustule count and/or rash severity per NCI CTC&#xD;
      version 4.0 with the use of topical pimecrolimus, without severe or intolerable toxicity is&#xD;
      demonstrated in this pilot study, further large scale studies of this therapy may be&#xD;
      warranted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Interim analysis shows no efficacy&#xD;
  </why_stopped>
  <start_date>February 2012</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants That do Not Experience Rash From Cetuximab Treatment on the Pimecrolimus Side of the Face.</measure>
    <time_frame>2 weeks</time_frame>
    <description>To determine if 1% pimecrolimus prevents the rash associated with treatment with cetuximab, as assessed by lesion counts on clinical photographs after two weeks of treatment.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Rash</condition>
  <arm_group>
    <arm_group_label>Pimecrolimus on Left vs. Placebo on Right</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will apply a thin layer of the Pimecrolimus cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pimecrolimus on Right vs. Placebo on Left</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will apply a thin layer of the Pimecrolimus cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimecrolimus</intervention_name>
    <description>Pimecrolimus 1% topical cream applied twice daily for four weeks on one side of the face.</description>
    <arm_group_label>Pimecrolimus on Left vs. Placebo on Right</arm_group_label>
    <arm_group_label>Pimecrolimus on Right vs. Placebo on Left</arm_group_label>
    <other_name>Elidel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo cream applied twice daily for four weeks on opposite side of the face from the Pimecrolimus side.</description>
    <arm_group_label>Pimecrolimus on Left vs. Placebo on Right</arm_group_label>
    <arm_group_label>Pimecrolimus on Right vs. Placebo on Left</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient is starting treatment with cetuximab at the WVU Cancer Center&#xD;
&#xD;
          -  Patient has advanced (unresectable or metastatic) malignancy&#xD;
&#xD;
          -  Patient is expected to remain on cetuximab treatment for at least 2 weeks after&#xD;
             enrollment on study.&#xD;
&#xD;
          -  Patients should be 18 years or older&#xD;
&#xD;
          -  Patients should not have a known contraindication to topical pimecrolimus therapy&#xD;
&#xD;
          -  Patients should have given written informed consent&#xD;
&#xD;
          -  Sexually active men and women of child bearing potential agree to use an effective&#xD;
             method of contraception during study participation and for three months afterwards.&#xD;
&#xD;
          -  Negative pregnancy test for woman of child bearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to topical pimecrolimus.&#xD;
&#xD;
          -  Patients with active or recent (within one month) infection in face&#xD;
&#xD;
          -  Psoriasis, eczema or others skin conditions not related to cetuximab involving face&#xD;
&#xD;
          -  Pregnant or nursing women&#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>Mohammed Almubarak, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West Virginia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West Virginia University Hospitals Mary Babb Randolph Cancer Center</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232. doi: 10.1016/1040-8428(94)00144-i. No abstract available.</citation>
    <PMID>7612182</PMID>
  </reference>
  <reference>
    <citation>Rusch V, Mendelsohn J, Dmitrovsky E. The epidermal growth factor receptor and its ligands as therapeutic targets in human tumors. Cytokine Growth Factor Rev. 1996 Aug;7(2):133-41. doi: 10.1016/1359-6101(96)00016-0.</citation>
    <PMID>8899291</PMID>
  </reference>
  <reference>
    <citation>Clark, R. Perez-Soler, L. Siu, A. Gordon and P. Santabarbara. Rash severity is predictive of increased survival with erlotinib HCl [abstract 786]. Proc Am Soc Clin Oncol 22 (2003),:p. 196.</citation>
  </reference>
  <reference>
    <citation>Mittmann N, Seung SJ. Rash rates with egfr inhibitors: meta-analysis. Curr Oncol. 2011 Apr;18(2):e54-63. doi: 10.3747/co.v18i2.605.</citation>
    <PMID>21505590</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>July 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>December 8, 2014</results_first_submitted>
  <results_first_submitted_qc>January 24, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2017</results_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cetuximab rash</keyword>
  <keyword>Erbitux rash</keyword>
  <keyword>Rash</keyword>
  <keyword>Pimecrolimus</keyword>
  <keyword>1% Topical pimecrolimus cream</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exanthema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pimecrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Left Side Investigational Cream/Placebo Cream on Right Side</title>
          <description>Patients will apply a thin layer of the investigational cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.&#xD;
Pimecrolimus: Pimecrolimus 1% topical cream twice daily for four weeks.</description>
        </group>
        <group group_id="P2">
          <title>Right Side Investigational Cream / Placebo on Left Side</title>
          <description>Patients will apply a thin layer of the investigational cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.&#xD;
Pimecrolimus: Pimecrolimus 1% topical cream twice daily for four weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Investigational Cream/Placebo Cream</title>
          <description>Patients will apply a thin layer of the investigational cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.&#xD;
Pimecrolimus: Pimecrolimus 1% topical cream twice daily for four weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;18 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;= 18 - 69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;= 70 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants That do Not Experience Rash From Cetuximab Treatment on the Pimecrolimus Side of the Face.</title>
        <description>To determine if 1% pimecrolimus prevents the rash associated with treatment with cetuximab, as assessed by lesion counts on clinical photographs after two weeks of treatment.</description>
        <time_frame>2 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Left sidePimecrolimus Cream</title>
            <description>The left side of the face that the Pimecrolimus Cream was applied.</description>
          </group>
          <group group_id="O2">
            <title>The Right Side the Pimecrolimus Cream</title>
            <description>The right side of the face that the pimecrolimus cream was applied.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants That do Not Experience Rash From Cetuximab Treatment on the Pimecrolimus Side of the Face.</title>
          <description>To determine if 1% pimecrolimus prevents the rash associated with treatment with cetuximab, as assessed by lesion counts on clinical photographs after two weeks of treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected for 1 year 9 months. The time from when the first participant went on the study until the last time the all the participants were off of the study.</time_frame>
      <desc>No difference in the definition. Adverse events that occur after the subject has signed the informed consent must be documented in the study database/case report forms, subject's medical records, and as required per additional institutional standards. Source documentation must be available to support all reported adverse events.&#xD;
Serious Adverse Events (SAE) requiring expedited reporting within 24 hours will also be reported to the Medical Director for Clinical Trials.</desc>
      <group_list>
        <group group_id="E1">
          <title>Investigational Cream/Placebo Cream</title>
          <description>Patients will apply a thin layer of the investigational cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.&#xD;
Pimecrolimus: Pimecrolimus 1% topical cream twice daily for four weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </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>
    <limitations_and_caveats>Changed Status to Terminated to indicate study closed early</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Mohammed Almubarak, MD, Assistant Professor</name_or_title>
      <organization>West Virginia University</organization>
      <phone>304-293-4229</phone>
      <email>malmubarak@hsc.wvu.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/NCT01692626
org study id: WVU21011
nct id: NCT01692626
lead sponsor: 
has dmc: Yes
When cancer patients are treated with the drug cetuximab they very often develop a rash.
      Usually it appears on their face and back and other parts of the body. The rash looks like
      acne and is treated with skin creams or antibiotics most of the time. The rash can become
      very painful and cause patients to stop using cetuximab to treat their cancer, even if
      cetuximab was helping fight their cancer.

      Cetuximab is known to be a good drug to help treat cancer. This study will help us learn
      about the rash cetuximab causes so hopefully future patients can finish taking cetuximab for
      their cancer. In this study the investigators will use a cream called pimecrolimus (Elidel)
      to see if it will help prevent the rash or keep the rash from getting worse. The
      investigators also want to see how the rash affects patients and their quality of life.

      Participants will be in this study for about four weeks if their rash does not get worse.
      They will need to apply the study cream and placebo two times daily and answer quality of
      life questionnaires during this study. Participants will also be seen by a dermatologist and
      have pictures taken of their rash.
Adult patients who are being treated with cetuximab for a malignancy will be offered the
      chance to take part in the study. Patients must provide written informed consent in order to
      participate in the study (including consent to clinical photographs).

      The area of skin to be treated with investigational cream will be the face. Baseline
      photographs will be taken of the selected area of bilateral face.

      Patients will be requested to apply a thin layer of the investigational cream twice daily to
      one half of face at the same time they are started on cetuximab. Patients will be provided
      with a placebo cream to apply to the other side of their face. Patients will be provided the
      sufficient investigational cream free of charge for the duration of study. The study
      coordinator will instruct the patient regarding which side of the face to apply the
      investigational cream. This will be randomly assigned by the study coordinator based on a
      randomization list generated by the biostatistics core and will only be known to the study
      coordinator. The dermatologist and study investigators will remain blinded to the side to
      which the investigational cream was applied. In this manner, patients will serve as their own
      controls. Patients are free to use oral tetracyclines if recommended by their primary
      oncologists. Patients on the trial, however, cannot use another rash treatment with the
      exception of moisturizing agents.

      Patients participating in the study will be instructed to apply a moisturizing cream, lotion,
      or ointment of their choice to the face three times a day. Moisturizers should be applied to
      the skin after, not before, the investigational cream application. Patients should not wet
      the treated area of skin for one hour after applying investigational cream, otherwise it
      could be washed off. The investigational cream should not be applied at or near the eyes.
      Patients on study will be instructed to minimize sun exposure and to avoid exposure to
      artificial sunlight. Patients should apply sunscreen to when exposed to sunlight, after the
      investigational cream has been completely absorbed into the skin.

      Patients will be given a copy of the Dermatology Life Quality Index (DLQI) questionnaire and
      asked to complete it on all study visits. Patients will be given help to complete the
      questionnaire if needed. The questionnaire and its interpretation are listed in the appendix.

      Patients will be assessed at least every two weeks in person. These visits may coincide with
      appointments with their primary oncologist for the treatment of their cancer. Patients will
      be able to contact the study coordinator during the duration of the study. Patients will also
      be requested to contact the study coordinator or investigators if the rash appears to worsen.

      The rash will be assessed by their treating oncologist during each study visit. Their
      treating oncologist will remain blinded to the side which the pimecrolimus cream was applied.
      Clinical photographs of the rash will be taken.

      When the rash appears predominantly on the side to which pimecrolimus was applied and the
      rash appears to worsen in the first 24 hrs of application of pimecrolimus then the patient
      will be considered allergic to pimecrolimus, and the treatment will be stopped.

      The rash will be compared at both sides of the face documented using the National Cancer
      Institute Common Terminology Criteria (NCI CTC) for acneiform rash. A papule and pustule
      count will also be determined by the study dermatologist and documented from the clinical
      photographs. Toxicity of topical pimecrolimus therapy will also be assessed as described in
      the appendix. Toxicity assessment will be described using NCI CTC Version 4. Toxicities
      observed will be defined as related (definitely, probably, possibly) or unrelated to topical
      pimecrolimus treatment.

      The total duration of the study will be for four weeks. After two weeks on topical
      pimecrolimus patients will be requested to come to a study visit. This will be coordinated
      with their usual oncologist visit if possible.

      After the rash assessment at this visit, the treating oncologist and the patient will be
      unblinded. If the intensity of the rash in the treated area is no worse than in the
      corresponding untreated area on the opposite side using the NCI CTC version 4 scale for
      acneiform rash, no severe toxicities occurred in the patient, and the patient finds the
      pimecrolimus therapy tolerable, the patient will continue on study. At this study visit,
      patients will also be given a copy of the DLQI and asked to complete it. Patients will be
      given help to complete the questionnaire by the study coordinator if needed. The
      questionnaire and its interpretation are listed in the appendix. Clinical photographs will be
      taken.

      Patients who experience a worsening of rash intensity by NCI CTC Version 4.0 at a treated
      area, or who suffer a severe toxicity (grade 3 or 4) related to topical pimecrolimus, or who
      find the topical pimecrolimus intolerable will discontinue use of pimecrolimus to that area
      immediately and will come off study.

      Patients who continue on study after the two week visit may apply a thin layer of 1% topical
      pimecrolimus twice daily to both sides of face.

      Patients who continue pimecrolimus therapy, beyond the initial rash assessment, will be
      re-assessed after two weeks in the same manner as at the initial rash assessment. Patients
      will remain on study for a maximum of 4 weeks since starting pimecrolimus therapy. At the 4
      week study visit, patients will also be given a copy of the DLQI and asked to complete it.
      Patients will be given help to complete the questionnaire by the study coordinator if needed.
      The questionnaire and its interpretation is listed in the appendix

      Patients who are considered to have benefited from pimecrolimus therapy at the 4 week visit
      may choose to use commercially available pimecrolimus off protocol but will be advised that
      the safety of topical pimecrolimus has not been established beyond one year of use, and that
      insurance might not cover for treatment.

      RATIONALE FOR STUDY DESIGN

      There is no highly-effective treatment for epidermal growth factor receptor (EGFR)-inhibitor
      induced rash. In this study patients will be offered 1% pimecrolimus cream, in addition to
      other standard non-topical therapy such as oral tetracycline antibiotics and moisturizing
      agents. Patients will apply 1% pimecrolimus cream to one side of the face at the time of
      starting cetuximab. The opposite untreated side will serve as the control side. In this
      controlled manner, if a decrease in papule and pustule count and/or rash severity per NCI CTC
      version 4.0 with the use of topical pimecrolimus, without severe or intolerable toxicity is
      demonstrated in this pilot study, further large scale studies of this therapy may be
      warranted.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
measure: Percentage of Participants That do Not Experience Rash From Cetuximab Treatment on the Pimecrolimus Side of the Face.
time frame: 2 weeks
description: To determine if 1% pimecrolimus prevents the rash associated with treatment with cetuximab, as assessed by lesion counts on clinical photographs after two weeks of treatment.
arm group label: Pimecrolimus on Left vs. Placebo on Right
arm group type: Experimental
description: Patients will apply a thin layer of the Pimecrolimus cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.
arm group label: Pimecrolimus on Right vs. Placebo on Left
arm group type: Experimental
description: Patients will apply a thin layer of the Pimecrolimus cream twice daily for four weeks (unless rash worsens sooner) to one half of face at the same time the are started on cetuximab. Patients will be provided with a placebo cream to apply to the other side of their face. The study coordinator will instruct the patient regarding which side of the face to apply the investigational cream. This will be randomly assigned by the study coordinator based on a randomization list generated by the biostatistics core and will only be known to the study coordinator.
intervention type: Drug
intervention name: Pimecrolimus
description: Pimecrolimus 1% topical cream applied twice daily for four weeks on one side of the face.
arm group label: Pimecrolimus on Left vs. Placebo on Right
arm group label: Pimecrolimus on Right vs. Placebo on Left
other name: Elidel
intervention type: Drug
intervention name: Placebo
description: Placebo cream applied twice daily for four weeks on opposite side of the face from the Pimecrolimus side.
arm group label: Pimecrolimus on Left vs. Placebo on Right
arm group label: Pimecrolimus on Right vs. Placebo on Left
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohammed Almubarak, MD
role: Principal Investigator
affiliation: West Virginia University
facility: 
country: United States
citation: Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232. doi: 10.1016/1040-8428(94)00144-i. No abstract available.
PMID: 7612182
citation: Rusch V, Mendelsohn J, Dmitrovsky E. The epidermal growth factor receptor and its ligands as therapeutic targets in human tumors. Cytokine Growth Factor Rev. 1996 Aug;7(2):133-41. doi: 10.1016/1359-6101(96)00016-0.
PMID: 8899291
citation: Clark, R. Perez-Soler, L. Siu, A. Gordon and P. Santabarbara. Rash severity is predictive of increased survival with erlotinib HCl [abstract 786]. Proc Am Soc Clin Oncol 22 (2003),:p. 196.
citation: Mittmann N, Seung SJ. Rash rates with egfr inhibitors: meta-analysis. Curr Oncol. 2011 Apr;18(2):e54-63. doi: 10.3747/co.v18i2.605.
PMID: 21505590
responsible party type: Sponsor
mesh term: Exanthema
mesh term: Pimecrolimus
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Changed Status to Terminated to indicate study closed early
point of contact: 