Comparison of Efficacy and Safety Between Medical Radiation Protectants (FORRAD®) and Trolamine (Biafine) for the Management of Radiation Dermatitis in Patients With Nasopharyngeal Carcinoma Receiving IMRT

Study Overview
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Brief Summary
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Radiation therapy remains the principal treatment for nasopharyngeal carcinoma (NPC). Although intensity modulated radiation therapy (IMRT) has been widely used in China nowadays, radiation dermatitis is still common. It has an impact on pain and quality of life, and if severe, may lead to interruption of the radiation schedule for the patient. Trolamine (Biafine; Genmedix Ltd, France) is commonly prescribed at the beginning of radiotherapy for preventing acute radiation-induced skin toxicity in China. However, as long as grade ≥2 radiation dermatitis is developed, trolamine is not allowed to use any more. Medical Radiation Protectants (FORRAD®) is a new kind of topical agents for prevention and treatment of radiation dermatitis. It could be used during the course of radiotherapy, even when grade ≥2 dermatitis is developed. This randomized phase II study is aimed to assess the effectiveness and safety of Medical Radiation Protectants (FORRAD®) for the prevention and treatment of acute radiation-induced dermatitis of grade 3 or higher during IMRT for patients with NPC, compared with trolamine.

Detailed Description
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Nasopharyngeal carcinoma (NPC) is one of the most common malignances in South China. Radiation therapy remains the principal treatment for NPC. One of the frequently occurred radiation-related side effects includes radiation-induced skin reactions (RISR), also known as radiation dermatitis, which affects up to 90% of cancer patients receiving radiation therapy. Although intensity modulated radiation therapy (IMRT) has been widely used in China nowadays, radiation dermatitis is still common. It is often characterized by edema, erythema, changes in pigmentation, fibrosis, and ulceration, and may cause signs and symptoms, such as skin dryness, itching discomfort, pain, warmth, and burning. Radiation dermatitis has an impact on pain and quality of life in this patient group, and if severe, may lead to interruption of the radiation schedule for the patient. A variety of interventions are used for prophylaxis and management of radiation dermatitis. However, a recent overview of systematic review and meta-analysis of randomized controlled trials concluded that the use of these interventions is not yet supported by conclusive evidence and therefore warrants further investigations. Trolamine (Biafine; Genmedix Ltd, France) is an oil-in-water emulsion that can enhance skin healing by recruiting macrophages and modifying the concentrations of various immunomodulators. In China, Trolamine is commonly prescribed at the beginning of radiotherapy for preventing acute radiation-induced skin toxicity. However, as long as grade ≥2 radiation dermatitis is developed, Trolamine is not allowed to use any more. Medical Radiation Protectants (FORRAD®) is a new kind of topical agents for prevention and treatment of radiation dermatitis. It could be used during the course of radiotherapy, even when grade ≥2 dermatitis is developed. The primary aim of this randomized phase II study is to assess the effectiveness and safety of Medical Radiation Protectants (FORRAD®) for the prevention and treatment of acute radiation-induced dermatitis of grade 3 or higher during IMRT for patients with NPC, compared with trolamine.

Official Title
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Comparison of Efficacy and Safety Between Medical Radiation Protectants (FORRAD®) and Trolamine (Biafine) for the Management of Radiation Dermatitis in Patients With Nasopharyngeal Carcinoma Receiving IMRT: A Single-center, Randomized Controlled Trial

Conditions
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Nasopharyngeal Neoplasms, Radiodermatitis

Intervention / Treatment
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* Drug: Medical Radiation Protectants (FORRAD®)
* Drug: Trolamine (Biafine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed and previously untreated nasopharyngeal carcinoma. Age ≥ 18 years and ≤ 65 years. Karnofsky performance status (KPS) score ≥ 70. No prior radiation or surgery in the head and neck. No contraindication to radiotherapy. Planned to receive radiotherapy alone or concurrent chemoradiotherapy, with intensity-modulated radiation therapy (IMRT). Adequate bone marrow function: while blood cell >= 3,000/μL, absolute neutrophil count >= 1,500/μL, hemoglobin >= 100g/L, platelet >= 75,000/μL. Life expectancy of >= 3 months. Exclusion Criteria: Known allergic reaction to any component of Medical Radiation Protectants (FORRAD®) or Trolamine (Biafine), or severe allergic constitution. Other conditions that the investigators consider as inappropriate for enrolling into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FORRAD group<br>This group of patients will receive Medical Radiation Protectants (FORRAD®) during study for prevention and treatment of acute radiation-induced dermatitis. This is the experimental group. | Drug: Medical Radiation Protectants (FORRAD®)<br>* Medical Radiation Protectants (FORRAD®) is prescribed at the beginning of radiotherapy for free. Patients are asked to start topical application of Medical Radiation Protectants (FORRAD®) on irradiated skin at the onset of radiotherapy, three times a day (30 minutes before radiotherapy, after radiotherapy, and before bedtime), until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation dermatitis. When grade 2 or higher radiation dermatitis is developed, patients can continue using Medical Radiation Protectants (FORRAD®). When grade 3 or higher radiation dermatitis happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted, until moist desquamation is cured.<br>|
| Active Comparator: Biafine group<br>This group of patients will receive Trolamine (Biafine) during study for prevention and treatment of acute radiation-induced dermatitis. This is the active comparator group. | Drug: Trolamine (Biafine)<br>* Trolamine (Biafine) is prescribed at the beginning of radiotherapy. Patients are asked to start topical application of trolamine (Biafine) on irradiated skin at the onset of radiotherapy, three times a day, until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation dermatitis. No other prophylactic creams, lotions, or gels are allowed. When grade 2 or higher radiation dermatitis is developed, patients cannot use trolamine any more, and they will receive other conventional medical care for treatment of radiation dermatitis in the investigators institution. When grade 3 or higher radiation dermatitis happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted, until moist desquamation is cured.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade ≥ 3 radiation dermatitis | Incidence of grade ≥ 3 radiation dermatitis according to CTCAE version 4.0 | Day 56 after completion or termination of radiotherapy | 
| The Skindex-16 | The skindex-16 is an analogue scale of symptoms and functional endpoints related to skin toxicity that may occur in the radiation treatment area. The mean AUC of Skindex-16 score over time. Patients were asked to complete the Skindex-16 only in reference to the skin receiving RT. | Day 56 after completion or termination of radiotherapy | 
| The symptom experience diary (SED) | The symptom experience diary (SED) required the patient to rate the severity of multiple skin toxicity-related signs and symptoms on a scale of 0 (do not experience) to 10 (experience all the time). | Day 56 after completion or termination of radiotherapy | 
| EORTC QLQ-C30 | EORTC QLQ-C30 is a Quality-of-Life Instrument proposed by the European Organization for Research and Treatment of Cancer (EORTC), for use in International Clinical Trials in Oncology. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. | Day 56 after completion or termination of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interruption time during the schedule of radiotherapy | The cumulative interruption time during the schedule of radiotherapy because of grade 3 or higher radiation dermatitis. | Through radiotherapy completion or termination, an average of 7 weeks | 
| Time for healing of radiation dermatitis | Time until healing of radiation dermatitis, after the completion or the termination of radiotherapy. | Through study completion, an average of 15 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasopharyngeal carcinoma (NPC), radiation dermatitis, intensity modulated radiation therapy (IMRT)