Topical Diclofenac for Prevention of Radiation-induced Dermatitis

Topical Diclofenac for Prevention of Radiation-induced Dermatitis: A Single-center, Randomized Controlled Trial

Radiation induced dermatitis (RID) is one of the leading adverse events of radiation therapy, and if occurred could alter the course of therapy. The main pathways of RID is inflammation and oxidative stress on local and systemic bases. The Diclofenac is a COX-2 inhibitor and Nonsteroidal anti-inflammatory drugs whose anti-inflammatory and antioxidant activities have been proven in several clinical trials. Thus, the aim of the present study is to evaluate the efficacy of Diclofenac sodium gel as a prophylactic method against the development of RID.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Head and Neck Tumor
• Intervention / Treatment: Drug: Diclofenac Sodium Gel; Other: Placebo gel

Detailed Description

Radiation induced dermatitis (RID) is one of the most commonly reported adverse events of Head and neck tumor, breast cancer radiation therapy (RT). Radiation therapy toxicity is exhibited within hours to weeks of exposure and persisting throughout the course of treatment. Radiation induced dermatitis is a result of generation of reactive oxygen species (ROSs), which in return induces epidermal and dermal inflammatory responses. Radiation causes structural tissue damage, which trigger production of pro-inflammatory mediators; as NF-κB, COX-2, and cytokines such as IL-6, TNF-a, and IFN- γ. Subsequently erythema, ulceration, and edema are developed，then followed by thinning of the epidermis, dry desquamation. If damage is more severe, moist desquamation occur. It can be deduced that inflammatory response plays a significant role in the radiotherapy induced dermatitis.

There are many agents that are used in the management of RID in the clinical settings, however, up till now there is none supported by the guidelines. Radiation induced dermatitis occurrence, not only could it impair the patient's quality of life but it could also affect the RT course of treatment, which could negatively influence the cancer treatment. Therefore more effort is needed to find a method of prevention of RID, resulting from Head and neck tumor,breast cancer RT.

Diclofenac sodium gel, a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (non-NSAID), is widely used to treat inflammatory conditions, and studies show that topical diclofenac has no safety concerns. It has been used for more than 20 years in patients with osteoarthritis without any significant adverse effects. The combination of diclofenac sodium as a COX-2 inhibitor and ionising radiation not only enhances the effect of radiation on tumour cells, but also improves radiation therapy for patients. Studies have shown that diclofenac sodium gel, through COX-2, can be used to prevent the development of capecitabine-induced hand-foot syndrome (HFS). RID upregulates COX-2 due to inflammatory stimulation, and COX-2 indirectly produces reactive oxygen species (ROS). The investigators conclude that diclofenac gel can reduce ROS by locally inhibiting COX-2 enzyme, thus preventing radiation dermatitis and reducing skin damage. Therefore, the investigators plan to conduct a study on the use of diclofenac sodium gel in radiation dermatitis to investigate the incidence of RID grade 2 and above at different time points after radiotherapy in patients with head and neck tumours, and whether it can reduce the incidence and severity of RID-related symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yuecan zeng; Phone Number: 19946610752; Email: wellyy2005@hainmc.edu.cn
• Study Contact Backup: Name: junnv xu; Phone Number: 18208946196; Email: xujunnv@sina.com

Study Locations

• China
  • Hainan
    • Haikou, Hainan, China, 570311
      • Recruiting
      • The Second Affiliated Hospital of Hainan Medical University
      • Contact: junnv xu, doctor; Phone Number: 18208946196; Email: xujunnv@sina.com
      • Contact: yuecan zeng, doctor; Phone Number: 19946610752; Email: wellyy2005@hainmc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female which are 18 years of age or older
2. Performance status < 2
3. Epithelial carcinoma of oropharynx, nasopharynx, larynx, hypopharynx, paranasal sinus and salivary glands or breast cancer, planned to receive a total dose of at least 50 Gy
4. The RTOG radiation dermatitis rating should be equal to 0 and the skin nutrition should be good
5. The main organs are functioning normally and meet the following standards: (1) Blood routine examination must meet the following criteria: (no blood transfusion within 14 days) a. HB ≥ 100g/L, b. WBC ≥3×10^9/L c. ANC≥1.5×10^9/L, d. PLT ≥100×10^9/L; (2) Biochemical examination must meet the following standards: a. BIL<1.5 times the upper limit of normal value (ULN), b. ALT and AST<2.5ULN, GPT ≤1.5×ULN; c. Serum Cr≤1 ULN, endogenous creatinine clearance rate>60ml/min (Cockcroft Gault formula);(3).Good coagulation function: defined as International standardized ratio (INR) or prothrombin time (PT) ≤1.5×ULN;(4).The myocardial enzyme spectra were in the normal range.
6. Patients willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the Clinical Investigation Plan tests and procedures.

Exclusion Criteria:

1. Pregnant or lactating women
2. A known history of intolerance or allergy to any component of the investigational product;
3. severe cardiopulmonary disease (such as unstable angina attacks, grade II cardiac insufficiency, acute myocardial infarction, acute episodes of chronic obstructive pulmonary disease, pulmonary heart disease);
4. The acute phase is accompanied by inflammatory skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, lichen planus, pityriasis rosea.
5. Systemic diseases known to delay the skin healing process, such as diabetes or severe kidney failure;
6. Skin rupture caused by malignant tumors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group（diclofenac sodium gel ）; In addition to routine skin care, diclofenac sodium gel was applied to the skin of the irradiated site triple a day a day from the date of first radiotherapy until end of radiotherapy or until the test side skin developed ≥grade 3 RID.Conventional health care:Minimize skin irritation, friction and excessive sun exposure in the irradiated area (level III to IV evidence), avoid wearing high-neck and tight clothing, and recommend low-neck tops. Subjects wash irradiated skin with water or wet towel, and wipe skin with dry towel to keep irradiated skin clean and dry.	Drug: Diclofenac Sodium Gel; Diclofenac Sodium Gel were applied to the skin of the irradiated site triple a day a day from the date of first radiotherapy until end of radiotherapy or until the test side skin developed ≥grade 3 RID.
Placebo Comparator: control group（Placebo Comparator）; In addition to routine skin care, Placebo gel was applied to the skin of the irradiated site triple a day a day from the date of first radiotherapy until end of radiotherapy or until the test side skin developed ≥grade 3 RID.Conventional health care:Minimize skin irritation, friction and excessive sun exposure in the irradiated area (level III to IV evidence), avoid wearing high-neck and tight clothing, and recommend low-neck tops. Subjects wash irradiated skin with water or wet towel, and wipe skin with dry towel to keep irradiated skin clean and dry.	Other: Placebo gel; The placebo does not contain the active ingredients of Jalosome, only the co-formulants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of development of grade ≥ 2 RID	If the patient developed grade ≥ 2 RID or not, RTOG standards were used for evaluation	From the first day of radiotherapy until 2 weeks after the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Time to develop grade ≥2 RID	EvaluationTime to develop grade ≥ 2 RID incidence, will be assessed by RTOG criteria based on the clinical presentation of Time to develop grade ≥2 RID	From the first day of radiotherapy until 2 weeks after the end of radiotherapy
Evaluation of Pain Intensity	Pain related assessment will be done through a Visual Analog Scale, with 0 being No pain and 10 being unbearable pain	From the first day of radiotherapy until 2 weeks after the end of radiotherapy
Evaluation of Incidence of Treatment-Emergent Adverse Events	Patients will be educated and instructed to report any adverse events	From the first day of radiotherapy through treatment completion(up to 7 weeks or 5 weeks)
Evaluation of Quality of life	Skin-related quality of life assessed through the Dermatology Life Quality Index (DLQI)	From the first day of radiotherapy until 2 weeks after the end of radiotherapy
Incidence of radiotherapy interruption	If the patient has been interrupted by RID or not	From the first day of radiotherapy through treatment completion (up to 7 weeks or 5 weeks)
The Concentration of inflammatory factors (IL-2、IL-4 、IL-6、IL-10、interferon-γ、TNF-α)	The differences in expression of inflammatory factors, such as IL-2 (pg/ml）,IL-4 (pg/ml）,IL-6 (pg/ml）,IL-10 (pg/ml）,interferon-γ（pg/ml） and TNF-α（pg/ml）.	Baseline（Day 0） and through study completion（Day 36 or Day 46）
The Concentration of inflammatory factors (WBC)	The differences in expression of inflammatory factors, such as WBC(10^9/L).	Baseline（Day 0） and through study completion（Day 36 or Day 46）
The Concentration of inflammatory factors (CRP)	The differences in expression of inflammatory factors, such as CRP（mg/L）.	Baseline（Day 0） and through study completion（Day 36 or Day 46）

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Hainan Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Prevention; Topical Diclofenac; Radiation-induced dermatitis; Head and Neck tumor; Brest Cancer
• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Radiation Injuries; Dermatitis; Skin and Connective Tissue Diseases; Breast Neoplasms; Head and Neck Neoplasms; Radiodermatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: 2025-K01-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No