<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/NCT02239731</url>
  </required_header>
  <id_info>
    <org_study_id>FDX104-1</org_study_id>
    <nct_id>NCT02239731</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Efficacy Study of Doxycycline Foam for the Prevention of EGFRI Skin Toxicity in Cancer Patients</brief_title>
  <official_title>A Safety, Tolerability and Efficacy Study of Doxycycline Topical Foam Administered Topically for Prevention of Epidermal Growth Factor Receptor Inhibition Skin Toxicity, to Subjects With Cancer Receiving Cetuximab or Panitumumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vyne Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vyne Therapeutics Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety, tolerability and efficacy of FDX104&#xD;
      Antibiotic Foam in the prevention of EGFRI skin toxicity in cancer patients receiving&#xD;
      Cetuximab or Panitumumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II multicenter, randomized, double blind, vehicle controlled clinical study&#xD;
      to evaluate the safety, tolerability and efficacy of Doxycycline Foam 4% for the prevention&#xD;
      of Epidermal Growth Factor Receptor Inhibition Skin Toxicity, to Subjects with Cancer&#xD;
      Receiving Cetuximab or Panitumumab on a weekly or every 2 weeks basis.&#xD;
&#xD;
      The study consists of a screening visit, a treatment period where patients will be treated&#xD;
      topically on the face twice daily for 5 weeks. A post-treatment follow up visit (4 weeks&#xD;
      after end of treatment), will be performed only for subjects who have experienced unresolved&#xD;
      possibly-related or related adverse events at the end of the treatment. Seven days after&#xD;
      randomization and study drug initiation, subjects will start their EGFRI treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To investigate the safety and tolerability of FDX104 in cancer patients receiving EGFRI</measure>
    <time_frame>9 weeks</time_frame>
    <description>To demonstrate the safety and tolerability of FDX104 in terms of skin tolerability, adverse events, serious adverse events and vital signs in subjects with advanced cancer treated by EGFRI.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Reduction of skin toxicity by FDX104 in cancer patients treated with EGFRI</measure>
    <time_frame>9 weeks</time_frame>
    <description>Reduction in numbers of papulo-pustular eruptions in the treatment side compared to the placebo treated side and reduction in erythema or edema areas in the treatment side compared to the placebo treated side estimated by the MESTT grading scale developed by the Multinational Association of Supportive Care in Cancer (MASCC) and by visual scale of rash severity (Scope A. scale)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Rash Due to Epidermal Growth Factor Receptor Inhibitors</condition>
  <arm_group>
    <arm_group_label>FDX104 (4% Doxycycline)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active ingredient: Doxycycline Concentration: 4% Route: Topical Dosage schedule: Twice daily, morning and evening. Prophylactic treatment to prevent the rash associated with EGFRI treatment. patients will apply a thin layer of the drug twice daily for five weeks to one half of face</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo foam</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Active ingredient: None Route: Topical Dosage schedule: Twice daily, morning and evening. Patients will apply a thin layer of the placebo twice daily for five weeks to the opposite half of the face of which they received active treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FDX104 (4% Doxycycline)</intervention_name>
    <description>FDX104 - 4% or Placebo to be applied twice twice daily during 5 weeks</description>
    <arm_group_label>FDX104 (4% Doxycycline)</arm_group_label>
    <arm_group_label>Placebo foam</arm_group_label>
    <other_name>FDX104 antibiotic foam</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 years and older&#xD;
&#xD;
          2. Subjects with any cancer receiving Cetuximab or Panitumumab on a weekly or every 2&#xD;
             weeks basis.&#xD;
&#xD;
          3. Scheduled to start Cetuximab or Panitumumab treatment;&#xD;
&#xD;
          4. Males or non-pregnant, non-lactating females who are postmenopausal, naturally or&#xD;
             surgically sterile, or with a negative subunit hCG pregnancy test immediately prior to&#xD;
             study entry.&#xD;
&#xD;
          5. Able to understand and provide signed informed consent.&#xD;
&#xD;
          6. Ability to reliably apply topical FDX104 and vehicle twice a day to the appropriate&#xD;
             part of the face&#xD;
&#xD;
          7. Willingness to minimize sun exposure for 5 weeks from randomization&#xD;
&#xD;
          8. ECOG performance status 0-2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior allergic reaction or severe intolerance to Doxcycycline and/or other&#xD;
             tetracyclines.&#xD;
&#xD;
          2. Prior allergic reaction or severe intolerance to soy or coconut oil&#xD;
&#xD;
          3. Cutaneous metastases on the face or might spread to the face.&#xD;
&#xD;
          4. The presence of any active skin disease (e.g., eczema), tattoos or other problems at&#xD;
             application site, (i.e., located on the face) that, in the investigator's opinion,&#xD;
             could confound the evaluation of the rash or make topical application unacceptable&#xD;
&#xD;
          5. Hair on the face (e.g beard) which would interfere with the application of the study&#xD;
             drug or its evaluation.&#xD;
&#xD;
          6. ANC &lt;1,500/mm3 (or&lt;1.5x109/L), or Platelet count &lt; 100,000/mm3 (or &lt;100x109/L)&#xD;
&#xD;
          7. Abnormal renal functions: Serum creatinine &gt;1.6 mg/dL or 142umol/L (SI units) or&#xD;
             calculated estimated creatinine clearance &lt;40 ml/min1.73 m2 based on Cockcroft and&#xD;
             Gault formula.&#xD;
&#xD;
          8. Abnormal hepatic functions: Serum Aspartate transaminase (AST) or alanine tansaminase&#xD;
             (ALT) &gt;5 institutional upper limit of normal (ULN). Or Total billirubin &gt; 2 x&#xD;
             institutional ULN or &gt;5 x institutional ULN if documented liver metastasis.&#xD;
&#xD;
          9. Any clinically significant safety laboratory results that, in the opinion of the&#xD;
             Investigator, would place the subject at undue risk if the subject were to participate&#xD;
             in the study&#xD;
&#xD;
         10. Any clinically significant finding on the physical examination that, in the opinion of&#xD;
             the Investigator, would place the subject at undue risk if the subject were to&#xD;
             participate in the study&#xD;
&#xD;
         11. Systemic lupus erythematosus&#xD;
&#xD;
         12. Undergoing any current biological treatment for cancer other than the prescribed EGFRI&#xD;
&#xD;
         13. Treatment with topical antibiotics, anti-acne medication and other topical treatments&#xD;
             on the face within 14 days prior to treatment start. Use of topical corticosteroids&#xD;
             within 2 weeks prior to baseline; only mild to moderate topical steroids are allowed&#xD;
             outside the head and neck area. The area should not exceed 10% of the whole body&#xD;
             surface area. In body folds, such as axillary and inguinal regions, only mild topical&#xD;
             steroids are allowed in short term use (≤15 consecutive days).&#xD;
&#xD;
         14. Treatment with systemic antibiotics 7 days prior to treatment start.&#xD;
&#xD;
         15. Known or suspected pregnancy, or lactation or planned pregnancy (females)&#xD;
&#xD;
         16. Previous enrolment in a clinical trial involving investigational drug or a medical&#xD;
             device within 30 days before provision of written informed consent for the study&#xD;
&#xD;
         17. Subjects who are mentally or physically unable to comply with all aspects of the&#xD;
             study.&#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>Ravit Geva, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sourasky Medical center, Tel-aviv, Israel</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Einat Shacham Shmueli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nirit Yarom, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assaf Harofeh medical center, Beer Yaakov, Israel</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Valerya Semenysty, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rambam Health Care Campus</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ayala Hubert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Medical Organization</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alexander Gluzman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Soroka University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hadas Prag Nave, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rabin Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Soroka Medical Center</name>
      <address>
        <city>Be'er-Sheva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah-Tikva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assaf Harofeh medical center</name>
      <address>
        <city>Rishon LeZion</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky medical center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba medical center</name>
      <address>
        <city>Tel Hashomer</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>February 25, 2018</last_update_submitted>
  <last_update_submitted_qc>February 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFRI</keyword>
  <keyword>Epidermal Growth Factor Receptor Inhibition</keyword>
  <keyword>Skin toxicity</keyword>
  <keyword>Topical</keyword>
  <keyword>Doxycycline</keyword>
  <keyword>Foam</keyword>
  <keyword>Phase II</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>Panitumumab</keyword>
  <keyword>Vectibix</keyword>
  <keyword>Erbitux</keyword>
  <keyword>Rash</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Doxycycline</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02239731
org study id: FDX104-1
nct id: NCT02239731
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety, tolerability and efficacy of FDX104
      Antibiotic Foam in the prevention of EGFRI skin toxicity in cancer patients receiving
      Cetuximab or Panitumumab.
This is a phase II multicenter, randomized, double blind, vehicle controlled clinical study
      to evaluate the safety, tolerability and efficacy of Doxycycline Foam 4% for the prevention
      of Epidermal Growth Factor Receptor Inhibition Skin Toxicity, to Subjects with Cancer
      Receiving Cetuximab or Panitumumab on a weekly or every 2 weeks basis.

      The study consists of a screening visit, a treatment period where patients will be treated
      topically on the face twice daily for 5 weeks. A post-treatment follow up visit (4 weeks
      after end of treatment), will be performed only for subjects who have experienced unresolved
      possibly-related or related adverse events at the end of the treatment. Seven days after
      randomization and study drug initiation, subjects will start their EGFRI treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To investigate the safety and tolerability of FDX104 in cancer patients receiving EGFRI
time frame: 9 weeks
description: To demonstrate the safety and tolerability of FDX104 in terms of skin tolerability, adverse events, serious adverse events and vital signs in subjects with advanced cancer treated by EGFRI.
measure: Reduction of skin toxicity by FDX104 in cancer patients treated with EGFRI
time frame: 9 weeks
description: Reduction in numbers of papulo-pustular eruptions in the treatment side compared to the placebo treated side and reduction in erythema or edema areas in the treatment side compared to the placebo treated side estimated by the MESTT grading scale developed by the Multinational Association of Supportive Care in Cancer (MASCC) and by visual scale of rash severity (Scope A. scale)
arm group label: FDX104 (4% Doxycycline)
arm group type: Experimental
description: Active ingredient: Doxycycline Concentration: 4% Route: Topical Dosage schedule: Twice daily, morning and evening. Prophylactic treatment to prevent the rash associated with EGFRI treatment. patients will apply a thin layer of the drug twice daily for five weeks to one half of face
arm group label: Placebo foam
arm group type: Placebo Comparator
description: Active ingredient: None Route: Topical Dosage schedule: Twice daily, morning and evening. Patients will apply a thin layer of the placebo twice daily for five weeks to the opposite half of the face of which they received active treatment.
intervention type: Drug
intervention name: FDX104 (4% Doxycycline)
description: FDX104 - 4% or Placebo to be applied twice twice daily during 5 weeks
arm group label: FDX104 (4% Doxycycline)
arm group label: Placebo foam
other name: FDX104 antibiotic foam
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ravit Geva, MD
role: Principal Investigator
affiliation: Sourasky Medical center, Tel-aviv, Israel
last name: Einat Shacham Shmueli, MD
role: Principal Investigator
affiliation: Sheba Medical Center
last name: Nirit Yarom, MD
role: Principal Investigator
affiliation: Assaf Harofeh medical center, Beer Yaakov, Israel
last name: Valerya Semenysty, MD
role: Principal Investigator
affiliation: Rambam Health Care Campus
last name: Ayala Hubert, MD
role: Principal Investigator
affiliation: Hadassah Medical Organization
last name: Alexander Gluzman, MD
role: Principal Investigator
affiliation: Soroka University Medical Center
last name: Hadas Prag Nave, MD
role: Principal Investigator
affiliation: Rabin Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Anti-Bacterial Agents
mesh term: Doxycycline