Evaluation of Fenofibrate on Radiation-induced Skin Injury

• ClinicalTrials.gov Identifier: NCT03557983
• Recruitment Status: Unknown
• First Posted: June 15, 2018
• Last Update Posted: June 15, 2018
• Sponsor: Second Affiliated Hospital of Soochow University
• Information provided by (Responsible Party): zhangshuyu, Second Affiliated Hospital of Soochow University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Radiodermatitis	Drug: Fenofibrate; Drug: Saline	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Evaluation of Fenofibrate on Radiation-induced Skin Injury
• Estimated Study Start Date: June 13, 2018
• Estimated Primary Completion Date: April 13, 2020
• Estimated Study Completion Date: April 13, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Measurement of skin wound area [ Time Frame: 3 months ]
   Skin wound area was measured by software-based analysis.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by Fenofibrate [ Time Frame: 3 months ]
   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).
2. Evaluation of skin injury [ Time Frame: 2 week ]
   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.
3. Evaluation of skin toxicity of radiotherapy [ Time Frame: 2 week ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Contacts

Contact: Shuyu Zhang, A/Prof.; 86+15851417273; zhang.shuyu@hotmail.com

Locations

China, Jiangsu

苏州大学

Suzhou, Jiangsu, China, 215123

Contact: Shuyu Zhang, A/Prof. 86+15851417273 zhang.shuyu@hotmail.com

Sponsors and Collaborators

Second Affiliated Hospital of Soochow University

Investigators

• Principal Investigator: Shuyu Zhang, A/Prof.; Soochow University

More Information

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. PPARα 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-α 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.

• Responsible Party: zhangshuyu, Shuyu Zhang Associate Professor, Second Affiliated Hospital of Soochow University
• ClinicalTrials.gov Identifier: NCT03557983
• Other Study ID Numbers: SoochowU
• First Posted: June 15, 2018
• Last Update Posted: June 15, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Radiodermatitis; Dermatitis; Skin Diseases; Radiation Injuries; Wounds and Injuries; Fenofibrate; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents