Evaluation of Fenofibrate on Radiation-induced Skin Injury

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.

Study Overview

• Status: Unknown
• Conditions: Radiodermatitis
• Intervention / Treatment: Drug: Fenofibrate; Drug: Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215123
      • 苏州大学

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: fenofibrate; Fenofibrate should be topically spread three times per day at the irradiated areas, with a concentration of 400 μg/mL for week.	Drug: Fenofibrate; 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.
PLACEBO_COMPARATOR: Saline; Saline is topically spread three times per day for one week.	Drug: Saline; Saline is topically spread three times per day at the irradiated areas for one week.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Shuyu Zhang, A/Prof., Soochow University

Publications and helpful links

General Publications

• Zhao Q, Cui Z, Zheng Y, Li Q, Xu C, Sheng X, Tao M, Xu H. Fenofibrate protects against acute myocardial I/R injury in rat by suppressing mitochondrial apoptosis as decreasing cleaved caspase-9 activation. Cancer Biomark. 2017 Jul 4;19(4):455-463. doi: 10.3233/CBM-170572.
• Kim EN, Lim JH, Kim MY, Kim HW, Park CW, Chang YS, Choi BS. PPARalpha agonist, fenofibrate, ameliorates age-related renal injury. Exp Gerontol. 2016 Aug;81:42-50. doi: 10.1016/j.exger.2016.04.021. Epub 2016 Apr 27.
• Liu J, Lu C, Li F, Wang H, He L, Hao Y, Chen AF, An H, Wang X, Hong T, Wang G. PPAR-alpha Agonist Fenofibrate Upregulates Tetrahydrobiopterin Level through Increasing the Expression of Guanosine 5'-Triphosphate Cyclohydrolase-I in Human Umbilical Vein Endothelial Cells. PPAR Res. 2011;2011:523520. doi: 10.1155/2011/523520. Epub 2011 Nov 16.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 13, 2018
• Primary Completion (ANTICIPATED): April 13, 2020
• Study Completion (ANTICIPATED): April 13, 2020

Study Registration Dates

• First Submitted: May 19, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (ACTUAL): June 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 15, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Wounds and Injuries; Dermatitis; Radiation Injuries; Radiodermatitis; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: SoochowU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No