<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/NCT01668498</url>
  </required_header>
  <id_info>
    <org_study_id>AIO-LQ-0110</org_study_id>
    <secondary_id>2010-022938-85</secondary_id>
    <nct_id>NCT01668498</nct_id>
  </id_info>
  <brief_title>Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of QoL in Patient With Ras-wt Colorectal Cancer</brief_title>
  <official_title>Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of Quality of Life in Patients With Ras-wildtype Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AIO-Studien-gGmbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AIO-Studien-gGmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      80 - 90 % of the patients treated with anti-EGFR antibodies (panitumumab or cetuximab)&#xD;
      experience skin toxicity, mostly acne like skin rash.&#xD;
&#xD;
      A standardized treatment of skin rash is neither established as standard arm for clinical&#xD;
      trials nor as guideline for the treatment of skin toxicity in clinical practice. While an&#xD;
      improvement of QoL has been demonstrated for panitumumab and cetuximab in comparison to best&#xD;
      supportive care the data basis for patient related outcomes regarding skin toxicity deriving&#xD;
      from randomized trials is still small.&#xD;
&#xD;
      Recent surveys among German oncologist revealed that physicians are reluctant to use oral&#xD;
      antibiotics as preemptive treatment . Only 19 out of 110 oncologists stated that they are&#xD;
      thinking about using preemptive treatment in patients with acne-like skin rash.&#xD;
&#xD;
      Thus, in the present trial two main questions will be addressed:&#xD;
&#xD;
      (i) Can preemptive treatment with oral doxycycline be replaced by a sequential skin treatment&#xD;
      strategy (i.e. local treatment with erythromycin followed by doxycycline in case of&#xD;
      inefficacy = development of acne) without compromising treatment efficacy of skin toxicity&#xD;
      treatment? (ii) Comparison of general and skin related QoL between both treatment arms.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2011</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">January 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients developing no skin toxicity ≥ grade 2</measure>
    <time_frame>8 weeks</time_frame>
    <description>Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>8 weeks</time_frame>
    <description>Quality of life will be assessed by standardized skin-related (DLQI) and global quality of life (EORTC QLQ C30.&#xD;
For correlation analyses between the different quality of life scores, the non-parametric test according to Spearman will preferably be applied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Skin toxicity</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assess different skin toxicity grading scales (i.e. NCI CTC v. 4.0; WoMo score; MESTT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between skin-related and global quality of life</measure>
    <time_frame>8 weeks</time_frame>
    <description>Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>late skin toxicity</measure>
    <time_frame>from week 8 to 12</time_frame>
    <description>Describe the development of late skin toxicity after 8 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin-toxicity related dose reductions of panitumumab</measure>
    <time_frame>8 weeks</time_frame>
    <description>Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">88</enrollment>
  <condition>Ras-wildtype Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Erythromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Arm (ARM A) skin- treatment: erythromycin cream 2% daily at bedtime doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2 skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Doxycyline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erythromycin</intervention_name>
    <description>Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.</description>
    <arm_group_label>Erythromycin</arm_group_label>
    <other_name>Aknemycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxycycline</intervention_name>
    <description>Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.</description>
    <arm_group_label>Doxycyline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with wild-type RAS (KRAS and NRAS) status of metastatic colorectal cancer&#xD;
             treatment with panitumumab according to label&#xD;
&#xD;
               -  RAS wild-type tested in&#xD;
&#xD;
               -  KRAS exon 2 (codons 12/13)&#xD;
&#xD;
               -  KRAS exon 3 (codons 59/61)&#xD;
&#xD;
               -  KRAS exon 4 (codons 117/146)&#xD;
&#xD;
               -  NRAS exon 2 (codons 12/13)&#xD;
&#xD;
               -  NRAS exon 3 (codons 59/61)&#xD;
&#xD;
               -  NRAS exon 4 (codons 117/146)&#xD;
&#xD;
          2. treatment with pre-emptive study medication shall begin the day before treatment start&#xD;
             with panitumumab&#xD;
&#xD;
          3. Willingness to cope with biweekly quality of life questionnaires&#xD;
&#xD;
          4. Written Informed consent&#xD;
&#xD;
          5. Aged at least 18 years&#xD;
&#xD;
          6. ECOG Performance Status 0-2&#xD;
&#xD;
          7. Life expectancy of at least 12 weeks&#xD;
&#xD;
          8. Adequate haematological, hepatic, renal and metabolic function parameters:&#xD;
&#xD;
               -  Leukocytes &gt; 3000/mm³&#xD;
&#xD;
               -  ANC ≥ 1500/mm³&#xD;
&#xD;
               -  Platelets ≥ 100,000/mm³&#xD;
&#xD;
               -  Haemoglobin &gt; 9 g/dl&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  GOT-GPT ≤ 2.5 x ULN (in case of liver metastases GOT / GPT ≤ 5 x ULN)&#xD;
&#xD;
               -  AP ≤ 5 x ULN&#xD;
&#xD;
               -  Magnesium, Calcium and potassium within normal ranges (may be substituted before&#xD;
                  study entry)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Subject pregnant or breast feeding, or planning to become pregnant within 6 months&#xD;
             after the end of treatment.&#xD;
&#xD;
          2. Subject (male or female) is not willing to use highly effective methods of&#xD;
             contraception (per institutional standard) during treatment and for 6 months (male or&#xD;
             female) after the end of treatment (adequate: oral contraceptives, intrauterine device&#xD;
             or barrier method in conjunction with spermicidal jelly).&#xD;
&#xD;
          3. Serious concurrent diseases&#xD;
&#xD;
          4. On-treatment participation in a clinical study in the period 30 days prior to&#xD;
             inclusion&#xD;
&#xD;
          5. Clinically significant cardiovascular disease in (incl. myocardial infarction,&#xD;
             unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac&#xD;
             arrhythmia) ≤ 1 year before enrolment.&#xD;
&#xD;
          6. History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or&#xD;
             evidence of interstitial lung disease on baseline chest CT scan.&#xD;
&#xD;
          7. History of HIV infection.&#xD;
&#xD;
          8. Other previous or concurrent malignancy (≤ 5 years prior to enrolment in study) except&#xD;
             non-melanoma skin cancer or cervical carcinoma FIGO stage 0- 1 if the patient is&#xD;
             continuously disease-free&#xD;
&#xD;
          9. Known allergic reactions on panitumumab, doxycycline or erythromycin&#xD;
&#xD;
         10. Previous treatment with anti-cancer agents directed against EGFR (e.g. cetuximab,&#xD;
             panitumumab, erlotinib, gefitinib, lapatinib)&#xD;
&#xD;
         11. Skin rash existing before or due to other reasons than panitumumab treatment&#xD;
&#xD;
         12. Other dermatologic disease that may interfere with correct grading of panitumumab&#xD;
             induced skin rash&#xD;
&#xD;
         13. Parallel treatment with anti-tumor agents other than panitumumab&#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>Melanie Kripp, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>III. Medizinische Klinik, Universitätsmedizin Mannheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Mannheim, III. Medizinische Klinik</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.aio-portal.de</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>April 18, 2016</last_update_submitted>
  <last_update_submitted_qc>April 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Can preemptive treatment of panitumumab mediated skin</keyword>
  <keyword>toxicity with oral doxycycline be replaced by local treatment with erythromycin?</keyword>
  <keyword>Panitumumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxycycline</mesh_term>
    <mesh_term>Erythromycin</mesh_term>
    <mesh_term>Erythromycin Estolate</mesh_term>
    <mesh_term>Erythromycin Ethylsuccinate</mesh_term>
    <mesh_term>Erythromycin stearate</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/NCT01668498
org study id: AIO-LQ-0110
secondary id: 2010-022938-85
nct id: NCT01668498
lead sponsor: 
has dmc: No
80 - 90 % of the patients treated with anti-EGFR antibodies (panitumumab or cetuximab)
      experience skin toxicity, mostly acne like skin rash.

      A standardized treatment of skin rash is neither established as standard arm for clinical
      trials nor as guideline for the treatment of skin toxicity in clinical practice. While an
      improvement of QoL has been demonstrated for panitumumab and cetuximab in comparison to best
      supportive care the data basis for patient related outcomes regarding skin toxicity deriving
      from randomized trials is still small.

      Recent surveys among German oncologist revealed that physicians are reluctant to use oral
      antibiotics as preemptive treatment . Only 19 out of 110 oncologists stated that they are
      thinking about using preemptive treatment in patients with acne-like skin rash.

      Thus, in the present trial two main questions will be addressed:

      (i) Can preemptive treatment with oral doxycycline be replaced by a sequential skin treatment
      strategy (i.e. local treatment with erythromycin followed by doxycycline in case of
      inefficacy = development of acne) without compromising treatment efficacy of skin toxicity
      treatment? (ii) Comparison of general and skin related QoL between both treatment arms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Percentage of patients developing no skin toxicity ≥ grade 2
time frame: 8 weeks
description: Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.
measure: Quality of life
time frame: 8 weeks
description: Quality of life will be assessed by standardized skin-related (DLQI) and global quality of life (EORTC QLQ C30.
For correlation analyses between the different quality of life scores, the non-parametric test according to Spearman will preferably be applied.
measure: Assess Skin toxicity
time frame: 8 weeks
description: Assess different skin toxicity grading scales (i.e. NCI CTC v. 4.0; WoMo score; MESTT)
measure: Correlation between skin-related and global quality of life
time frame: 8 weeks
description: Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.
measure: late skin toxicity
time frame: from week 8 to 12
description: Describe the development of late skin toxicity after 8 weeks
measure: Skin-toxicity related dose reductions of panitumumab
time frame: 8 weeks
description: Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab
arm group label: Erythromycin
arm group type: Experimental
description: Experimental Arm (ARM A) skin- treatment: erythromycin cream 2% daily at bedtime doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2 skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
arm group label: Doxycyline
arm group type: Active Comparator
description: Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
intervention type: Drug
intervention name: Erythromycin
description: Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.
arm group label: Erythromycin
other name: Aknemycin
intervention type: Drug
intervention name: Doxycycline
description: Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.
arm group label: Doxycyline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Melanie Kripp, Dr. med.
role: Principal Investigator
affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim
facility: 
country: Germany
url: http://www.aio-portal.de
description: Related Info
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Doxycycline
mesh term: Erythromycin
mesh term: Erythromycin Estolate
mesh term: Erythromycin Ethylsuccinate
mesh term: Erythromycin stearate