Evaluation of Fenofibrate on Radiation-induced Skin Injury

Study Overview
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Brief Summary
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Fenofibrate is a specific ligand for PPARα, which has been used for the treatment of hypercholesterolemia, hypertriglyceridemia, diabetes and cardiovascular diseases for long time. Fenofibrate reduces low-density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglyceride levels, while increases high-density lipoprotein (HDL) levels. PPARα has also shown antioxidant and anti-inflammatory properties. Fenofibrate confers cytoprotective effect against myocardial ischemia-reperfusion (I/R) injury in rats by suppressing cell apoptosis and ameliorates age-related renal injury through the activation of AMPK and SIRT1 signaling. However, the safety and effectiveness of fenofibrate on the progression of radiation-induced skin injury remain unknown. The purpose of this study is to determine whether topical application of fenofibrate is safe and effective for radiation-induced skin injury.

Detailed Description
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Radiation-induced skin injury is a significant side effect of ionizing radiation delivered to the skin during cancer treatment as well as a result of other exposure to radiation. The skin is one of radiosensitive organ systems in human body because it is a continuously renewing organ containing rapidly proliferating and maturing cells. Ionizing radiation promotes reactive nitrogen and oxygen species (RNS/ROS) production due to radiolysis of water and direct ionization of target molecules, which result in oxidative damage and skin injuries. It is considered that  95 % of cancer patients receiving radiation therapy will develop some form of radiodermatitis, including erythema, dry desquamation, and moist desquamation. Radiation-induced skin injury negatively affects the process of radiotherapy and the quality of patients' life. Despite substantial improvements in radiation technology, radiation-induced skin toxicity is still a concerning problem. The purpose of this study is to determine whether topical application of fenofibrate is safe and effective for radiation-induced skin injury.

Official Title
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Evaluation of Fenofibrate on Radiation-induced Skin Injury

Conditions
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Radiodermatitis

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients had to have a pathologically proven cancer with a planned course of radiotherapy. Normal haematological function (granulocyte count > 1.5 X 109 cells per litre, platelet count > 100 X 109 cells per litre and haemoglobin > 100 g/L) and organ function (creatinine clearance > 50 mL/min) and aspartate aminotransferase/alanine aminotransferase < 2.5 of upper normal limit). Exclusion Criteria: The presence of rash or unhealed wound in the radiation field, known allergy or hypersensitivity to fenofibrate, pregnancy or lactation, history of/current connective tissue disorder and prior radiation to the thorax.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fenofibrate<br>Fenofibrate should be topically spread three times per day at the irradiated areas, with a concentration of 400 μg/mL for week. | Drug: Fenofibrate<br>* Fenofibrate is dissolved in Saline and topically spread three times per day at the irradiated areas, with a concentration of 400 μg/mL for week.<br>|
| Placebo Comparator: Saline<br>Saline is topically spread three times per day for one week. | Drug: Saline<br>* Saline is topically spread three times per day at the irradiated areas for one week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of skin wound area | Skin wound area was measured by software-based analysis. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by Fenofibrate | Toxicity of Fenofibrate was graded using the NCI Common Terminology Criteria for Adverse Events v. 3.0. Any adverse event. Grade 1 attributed to fenofibrate was considered dose-limiting toxicity (DLT). | 3 months | 
| Evaluation of skin injury | Skin toxicity of radiotherapy was evaluated every day, once radiation began. Fenofibrate administration was given immediately when Grade 1 dermatitis occurred, and then dermatitis was recorded weekly. The score at the end of radiotherapy was the one of the last week of radiotherapy. The evaluation continued until 2 weeks after the end of radiotherapy with two approaches. The standard was the RTOG score defined by the observers. | 2 week | 
| Evaluation of skin toxicity of radiotherapy | Skin toxicity of radiotherapy was evaluated every day, once radiation began. Fenofibrate administration was given immediately when Grade 1 dermatitis occurred, and then dermatitis was recorded weekly. The score at the end of radiotherapy was the one of the last week of radiotherapy. The evaluation continued until 2 weeks after the end of radiotherapy with two approaches. Patient-reported symptom scores was adapted from the Skin Toxicity Assessment Tool as pain, burning, itching, pulling and tenderness in the treatment area. | 2 week |