<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/NCT01688479</url>
  </required_header>
  <id_info>
    <org_study_id>Calendula trial</org_study_id>
    <nct_id>NCT01688479</nct_id>
  </id_info>
  <brief_title>Trial Comparing Calendula Officinalis With Aqueous Cream &quot;Essex&quot; to Treat Skin Reactions From Radiotherapy of Breast Cancer</brief_title>
  <official_title>Randomized, Blinded Phase III Trial Comparing Calendula Officinalis Cream With Standard Aqueous Cream &quot;Essex&quot; for Treatment of Skin Reactions Caused by Postoperative Radiotherapy of Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute radiation skin reactions (ARSR) occur in the majority of patients undergoing&#xD;
      postoperative radiotherapy (RT). Some patients experience more severe reactions such as dry&#xD;
      and/or moist desquamation but most patients experience mild reactions e.g. erythema (Lopez et&#xD;
      al., 2005). The radiation dose, volume, RT technique and previous treatment, such as type of&#xD;
      surgery and previous chemotherapy, are factors that might impact on the risk for ARSR&#xD;
      together with patient-related factors such as body mass index (BMI), smoking status and&#xD;
      previous skin damage (Porock et al., 1998; Wells et al., 2004). In a pilot study (n=93) of&#xD;
      the frequency of ARSR in patients with breast cancer who underwent adjuvant RT it was shown&#xD;
      that 93% developed ARSR, mostly mild reactions. Patients reported low scores on pain and&#xD;
      itching (Sharp et al., 2011). Over 80% of the patients reported adherence to the skin care&#xD;
      recommendations which included application of a thin layer of Essex® cream, a non-perfumed&#xD;
      aqueous cream, on the irradiated area at least two times a day (Sharp et al., 2011). The&#xD;
      effects of skin care products containing Calendula Officinalis (marigold plant) on ARSR in&#xD;
      patients with breast cancer were investigated in a randomized clinical trial (Pommier et al.,&#xD;
      2004). Patients in the experimental group, treated with calendula cream had a statistically&#xD;
      significant lower incidence of severe ARSR, pain and treatment interruptions in comparison&#xD;
      with the patients in the control group, treated with trolamine.&#xD;
&#xD;
      The purpose of this blinded, randomized clinical trial is to compare two topical agents,&#xD;
      Calendula Weleda® cream and Essex® cream, in terms of efficacy to reduce the risk of severe&#xD;
      acute radiation skin reactions (ARSR) in relation to adjuvant radiotherapy (RT) for breast&#xD;
      cancer.&#xD;
&#xD;
      Patients were instructed to apply a thin layer of the assigned cream twice a day, starting at&#xD;
      the onset of RT and continue until two weeks after termination, or until the ARSR is healed.&#xD;
      The application should include the whole treatment area including the armpit and&#xD;
      shoulder/back area in patients treated with modified radical mastectomy. Patients are also&#xD;
      advised to not apply the cream within two hours before the RT in order to avoid possible&#xD;
      build-up effect. Daily wash with perfume free soap and tap water are recommended and patients&#xD;
      are advised to refrain from use of other topical agents in the irradiated area.&#xD;
&#xD;
      The primary endpoint is the efficacy to reduce acute radiation skin reactions (ARSR),&#xD;
      assessed with the Radiation Therapy Oncology Group/The Organization for Research and&#xD;
      Treatment of Cancer Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale) at&#xD;
      follow-up.&#xD;
&#xD;
      Secondary endpoints include patient reported outcome measures; Quality of Life Questionnaire&#xD;
      (QLQ-C30), Sleep disturbances (MOS-sleep questionnaire) and symptoms experienced from the&#xD;
      irradiated area (visual analogue scale). Patients' experiences and adherence to the topical&#xD;
      agents are also evaluated.&#xD;
&#xD;
      A total of 400 patients are required to detect a true absolute reduction in the proportion of&#xD;
      patients with ARSR, from 35% with standard treatment (Essex® cream) to 20% with the&#xD;
      experimental treatment (Calendula Weleda® cream), with a significance level of 5% a power of&#xD;
      90%. With this sample size, 95% confidence intervals for the difference in proportions are&#xD;
      estimated to be in the order of ±10%. Assuming a rate of 5% of non-responders, the target&#xD;
      size has been set to 420 patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2011</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Grade of skin reactions to radiotherapy</measure>
    <time_frame>8 weeks</time_frame>
    <description>Skin reactions due to radiotherapy using RTOG scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life in relation to skin reaction</measure>
    <time_frame>8 weeks</time_frame>
    <description>Measurements of sleep disturbances acc. to the MOS-SLEEP scale and QoL acc. to EORTC QLQ-C30</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Impact of smoking habits on the intensity of the skin reaction</measure>
    <time_frame>8 weeks</time_frame>
    <description>Collection of data on smoking habits and measurements of carbon monoxide in exhaled air</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">420</enrollment>
  <condition>Postoperative Radiotherapy Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Calendula Weleda® cream (Weleda)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Calendula Officinalis (marigold plant) is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Essex® cream (Schering-Plough)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Essex cream is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calendula Weleda cream (Weleda AG, Sweden) contains extracts of marigold plant (Calendula Officinalis 10%), wool fat and sesame oil</intervention_name>
    <arm_group_label>Calendula Weleda® cream (Weleda)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Essex® cream (Schering-Plough), aqueous cream without parabens</intervention_name>
    <arm_group_label>Essex® cream (Schering-Plough)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  radically operated for breast cancer,&#xD;
&#xD;
          -  aged 18 years or older,&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous radiation in the same area,&#xD;
&#xD;
          -  severe general health problems,&#xD;
&#xD;
          -  ECOG performance status &gt; 3,&#xD;
&#xD;
          -  reduced cognitive ability,&#xD;
&#xD;
          -  allergy to marigold plant&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria AC Bergenmar, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lena Sharp, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thomas Hatschek, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Oncology, Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>17176</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <results_reference>
    <citation>Sharp L, Finnila K, Johansson H, Abrahamsson M, Hatschek T, Bergenmar M. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions--results from a randomised blinded trial. Eur J Oncol Nurs. 2013 Aug;17(4):429-35. doi: 10.1016/j.ejon.2012.11.003. Epub 2012 Dec 13.</citation>
    <PMID>23245940</PMID>
  </results_reference>
  <results_reference>
    <citation>Sharp L, Johansson H, Hatschek T, Bergenmar M. Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer. Breast. 2013 Oct;22(5):634-8. doi: 10.1016/j.breast.2013.07.047. Epub 2013 Aug 13.</citation>
    <PMID>23953136</PMID>
  </results_reference>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>September 15, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>September 16, 2015</last_update_submitted>
  <last_update_submitted_qc>September 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Thomas Hatschek</investigator_full_name>
    <investigator_title>MD, PhD, Assoc. prof.</investigator_title>
  </responsible_party>
  <keyword>Postoperative radiotherapy</keyword>
  <keyword>breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_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/NCT01688479
org study id: Calendula trial
nct id: NCT01688479
lead sponsor: 
has dmc: No
Acute radiation skin reactions (ARSR) occur in the majority of patients undergoing
      postoperative radiotherapy (RT). Some patients experience more severe reactions such as dry
      and/or moist desquamation but most patients experience mild reactions e.g. erythema (Lopez et
      al., 2005). The radiation dose, volume, RT technique and previous treatment, such as type of
      surgery and previous chemotherapy, are factors that might impact on the risk for ARSR
      together with patient-related factors such as body mass index (BMI), smoking status and
      previous skin damage (Porock et al., 1998; Wells et al., 2004). In a pilot study (n=93) of
      the frequency of ARSR in patients with breast cancer who underwent adjuvant RT it was shown
      that 93% developed ARSR, mostly mild reactions. Patients reported low scores on pain and
      itching (Sharp et al., 2011). Over 80% of the patients reported adherence to the skin care
      recommendations which included application of a thin layer of Essex® cream, a non-perfumed
      aqueous cream, on the irradiated area at least two times a day (Sharp et al., 2011). The
      effects of skin care products containing Calendula Officinalis (marigold plant) on ARSR in
      patients with breast cancer were investigated in a randomized clinical trial (Pommier et al.,
      2004). Patients in the experimental group, treated with calendula cream had a statistically
      significant lower incidence of severe ARSR, pain and treatment interruptions in comparison
      with the patients in the control group, treated with trolamine.

      The purpose of this blinded, randomized clinical trial is to compare two topical agents,
      Calendula Weleda® cream and Essex® cream, in terms of efficacy to reduce the risk of severe
      acute radiation skin reactions (ARSR) in relation to adjuvant radiotherapy (RT) for breast
      cancer.

      Patients were instructed to apply a thin layer of the assigned cream twice a day, starting at
      the onset of RT and continue until two weeks after termination, or until the ARSR is healed.
      The application should include the whole treatment area including the armpit and
      shoulder/back area in patients treated with modified radical mastectomy. Patients are also
      advised to not apply the cream within two hours before the RT in order to avoid possible
      build-up effect. Daily wash with perfume free soap and tap water are recommended and patients
      are advised to refrain from use of other topical agents in the irradiated area.

      The primary endpoint is the efficacy to reduce acute radiation skin reactions (ARSR),
      assessed with the Radiation Therapy Oncology Group/The Organization for Research and
      Treatment of Cancer Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale) at
      follow-up.

      Secondary endpoints include patient reported outcome measures; Quality of Life Questionnaire
      (QLQ-C30), Sleep disturbances (MOS-sleep questionnaire) and symptoms experienced from the
      irradiated area (visual analogue scale). Patients' experiences and adherence to the topical
      agents are also evaluated.

      A total of 400 patients are required to detect a true absolute reduction in the proportion of
      patients with ARSR, from 35% with standard treatment (Essex® cream) to 20% with the
      experimental treatment (Calendula Weleda® cream), with a significance level of 5% a power of
      90%. With this sample size, 95% confidence intervals for the difference in proportions are
      estimated to be in the order of ±10%. Assuming a rate of 5% of non-responders, the target
      size has been set to 420 patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Grade of skin reactions to radiotherapy
time frame: 8 weeks
description: Skin reactions due to radiotherapy using RTOG scale
measure: Quality of life in relation to skin reaction
time frame: 8 weeks
description: Measurements of sleep disturbances acc. to the MOS-SLEEP scale and QoL acc. to EORTC QLQ-C30
measure: Impact of smoking habits on the intensity of the skin reaction
time frame: 8 weeks
description: Collection of data on smoking habits and measurements of carbon monoxide in exhaled air
arm group label: Calendula Weleda® cream (Weleda)
arm group type: Experimental
description: Calendula Officinalis (marigold plant) is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided
arm group label: Essex® cream (Schering-Plough)
arm group type: Active Comparator
description: Essex cream is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided
intervention type: Drug
intervention name: Calendula Weleda cream (Weleda AG, Sweden) contains extracts of marigold plant (Calendula Officinalis 10%), wool fat and sesame oil
arm group label: Calendula Weleda® cream (Weleda)
intervention type: Drug
intervention name: Essex® cream (Schering-Plough), aqueous cream without parabens
arm group label: Essex® cream (Schering-Plough)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria AC Bergenmar, PhD
role: Principal Investigator
affiliation: Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden
last name: Lena Sharp, PhD
role: Principal Investigator
affiliation: Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden
last name: Thomas Hatschek, MD, PhD
role: Study Chair
affiliation: Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden
facility: 
country: Sweden
citation: Sharp L, Finnila K, Johansson H, Abrahamsson M, Hatschek T, Bergenmar M. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions--results from a randomised blinded trial. Eur J Oncol Nurs. 2013 Aug;17(4):429-35. doi: 10.1016/j.ejon.2012.11.003. Epub 2012 Dec 13.
PMID: 23245940
citation: Sharp L, Johansson H, Hatschek T, Bergenmar M. Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer. Breast. 2013 Oct;22(5):634-8. doi: 10.1016/j.breast.2013.07.047. Epub 2013 Aug 13.
PMID: 23953136
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Thomas Hatschek
investigator title: MD, PhD, Assoc. prof.
mesh term: Breast Neoplasms