Cicaderma Efficacy vs Standard Care of Sites in Preventing Radiodermatitis in Non-metastatic Breast Cancer Patients

Study Overview
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Brief Summary
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Phase III, prospective, interventional, multicentric, comparative, randomized, open study with 2 parallel arms, evaluating the efficacy of Cicaderma ointment vs standard management of each site in preventing the onset of grade > 2 radiodermatitis according to the National Cancer Institute - Common Terminology Criteria for Adverse Events-Version (NCI-CTCAE-V5)

Detailed Description
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Breast cancer is the most common cancer in women. It accounts for more than 1/3 of new cancer cases and is the 1st cause of death for women. Management usually includes tumorectomy or mastectomy precede or not by a chemotherapy, then adjuvant irradiation that can be supplemented with adjuvant chemotherapy and / or hormone therapy. Radiotherapy uses ionizing radiation (photons, electrons ...) to destroy cancer cells and consists in precisely directing these radiations on the area to be treated while preserving as much as possible healthy tissues and surrounding organs. Radiation-induced dermatitis is a skin lesion that occurs after exposure to ionizing radiation and is commonly seen in patients. Acute radiodermatitis occurs in the days or weeks following the start of irradiation with different degrees of severity (dry or exsudative radiodermatitis, acute radionecrosis) They are responsible for an alteration of patients' quality of life (pain, sensitivity to UV radiation, discomfort sensations ...), which may lead to a temporary or even permanent therapeutic interruption and reduce the probability of tumor control. The management of these dermatitis is very heterogeneous, no study having demonstrated the superiority of a preventive or curative treatment. Trolamine (Biafine®) is to date the only topic with a Marketing Authorization (MA) for the treatment of radiation-induced secondary erythema. A study conducted on 254 patients at the Léon Bérard Center from 1999 to 2001 demonstrated that the preventive use of a calendula-based topical was associated with a statistically significant reduction of grade 2 radiodermitis compared to trolamine in patients presenting an early breast cancer treated with post-operative irradiation. However, this calendula ointment, which does not have the MA in the indicated indication, was in practice more difficult to apply than trolamine. Currently, skin hygiene measures to be applied are systematically explained to patients before carrying out post-operative radiotherapy (cotton clothing, neutral soap, etc.). Some centers such as Center Léon Bérard recommend the systematic use of a topic after each session, while others recommend hygiene measures or implement other options (essential oils ...). However, the effectiveness of these current practices on the prevention of radiodermatitis has not yet been demonstrated. It is a phase III, prospective, interventional, multicentric, comparative, randomized, open study with 2 parallel arms Patients will be randomized (1 :1) in Arm A (hygiene measures + preventive treatment with Cicaderma ointment) or Arm B (preventive treatment according to the site recommendations (at least the hygiene measures) with a stratification (site, body mass index ≤25 vs >25 and RT hypofractionning).

Official Title
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Randomised Multicentric Phase III Study Evaluating the Efficacy of Cicaderma vs Standard Management of Each Site in Preventing Radiodermatitis After Adjuvant Post-operative Breast Irradiation in Patients With Non-metastatic Breast Cancer

Conditions
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Breast Adenocarcinoma, Radiation Dermatitis, Radiation Toxicity

Intervention / Treatment
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* Drug: cicaderma + simple hygiene rules
* Other: Simple hygiene rules and a maximum of one topical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Patient requiring a post-operative radiotherapy (post mastectomy or tumorectomy) for a mammary adenocarcinoma or an unilateral in situ breast cancer histologically documented, early stage of disease (non metastatic) Patient with no residual tumor (R0 or R1) Patient informed and having given her signed consent Patient affiliated to a social security regimen Exclusion Criteria: Unsolved cutaneous toxicities of any previous treatment Hormonotherapy started prior to radiotherapy Concomitant use of other topical treatments than the study treatments on the irradiated area Patient treated by concomitant chemotherapy and/or targeted therapy Known hypersensibility to at least one component of the topicals used or Cicadema ointment Patient for whom follow-up does not seem possible even in the short term Pregnant or breastfeeding woman Participation in another clinical trial that may interfere with the evaluation of the primary endpoint Patient Under tutorship or curatorship or deprived of liberty

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, multicentric Phase III study evaluating the Cicaderma ointment efficacy versus standard practice of each site in the prevention of radiodermatitis in patients presenting a non metastatic breast cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simple hygiene rules of the site + Cicaderma ointment<br>Hygiene rules (use of a neutral soap, no bath, use of non-alcoholic products, delicate drying of the skin, wearing of cotton clothing) and Cicaderma ointment application) | Drug: cicaderma + simple hygiene rules<br>* Cicaderma ointment (2 applications / day: after the radiotherapy session) and in the evening) + simple hygiene rules<br>* Other names: Cicaderma ointment and simple hygiene rules;|
| Active Comparator: Preventive standard cares<br>Preventive standard cares of the site including hygiene rules (use of a neutral soap, no bath, use of non-alcoholic products, delicate drying of the skin, wearing of cotton clothing) and a maximum of one topical treatment | Other: Simple hygiene rules and a maximum of one topical treatment<br>* Simple hygiene rules according to the site recommandations including eventually a maximum of one topical treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Cicaderma ointment efficacy versus the standard management of each site in preventing the onset of grade >= 2 radiodermatitis (NCI-CTCAE-V5) | Number of patients presenting >= 2 radiodermatitis according to the National Cancer Institute - Common Terminology Criteria for Adverse Events-Version (NCI-CTCAE-V5) | Up to 30+/-4 days after the end of radiotherapy interruption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' satisfaction | Patients' satisfaction evaluated using the Patient's evaluation of the preventive management of radiodermatits - Likert scale in 5 points (from very unsatisfied to very satisfied) | 30+/-4 days after the end of radiotherapy interruption | 
| Patients' quality of life: DLQI questionnaire | Patients' quality of life evaluated using the Dermatology Life Quality Index (DLQI) questionnaire (validated questionnaire composed of 10 items leading to a global score) | Up to 30+/-4 days after the end of radiotherapy interruption | 
| Patients' pain in the irradiated area: numeric scale | Patients' pain evaluated using a numeric scale from 0 (no pain) to 10 (unbearable pain) | Up to 30+/-4 days after the end of radiotherapy interruption | 
| Rate of temporary or permanent RT interruption related to the onset of grade 3 radiodermatitis | Temporary or permanent radiotherapy interruption related to the onset of grade 3 radiodermatitis observed during patients' treatment period | Through radiotherapy completion, an average of 5 weeks | 
| Rate of prurit onset whatever the grade | Prurit onset whatever the grade observed | Up to 30+/-4 days after the end of radiotherapy interruption | 
| Doses of radiation therapy received | Doses of radiation therapy received during each radiotherapy session | Through radiotherapy completion, an average of 5 weeks | 
| Delay of onset of the first cutaneous event (radiodermatitis or prurit) grade ≥2 | Onset of the first grade >= 2 cutaneous event (radiodermatitis or prurit) | Up to 30+/-4 days after the end of radiotherapy | 
| Compliance with the Cicaderma ointment application (experimental arm) | Compliance evaluated according to the ointment tubes brought back by the patients (not used or partially used) and patient's diary | Up to 30+/-4 days after the end of radiotherapy | 
| Determination of the factors measured prior to treatment initiation which are associated to the onset of grade ≥2 radiodermatitis (cup size) | Cup size | At inclusion | 
| Determination of the factors measured prior to treatment initiation which are associated to the onset of grade ≥2 radiodermatitis (phototype) | Phototype | At inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-metastatic breast cancer, Post operative adjuvant radiotherapy, Radiotherapy cutaneous toxicity