Radiation Dermatitis Acute, Radiation Dermatitis, Fibrosis; Skin
Conditions
Keywords
Catechins, Radiation Dermatitis
Brief summary
Introduction Radiation-induced dermatitis (RID), which includes both acute and chronic forms, affects up to 95% of patients undergoing radiation therapy. Despite its high incidence, there are currently no validated prevention and management recommendations specifically for the mexican population. Catechins, particularly epigallocatechin gallate and epicatechin, are emerging as a promising and readily accessible therapeutic option for radiation damage in skin and other organs, including conditions like esophagitis, intestinal injury, and mucositis. Objective This study aims to evaluate the utility of oral or topical catechins in preventing and managing acute and chronic radiation-induced dermatitis in cancer patients, comparing their effectiveness against standard treatment. Material and Methods This will be a randomized, double-blind, phase III clinical trial with a longitudinal and comparative design. Patients will be allocated into two primary study groups: prevention (n=81) and treatment (n=81). Each group will be further divided into four treatment arms: Epigallocatechin gallate (experimental aerosol) Epicatechin (experimental capsule) Saline control arm (aerosol) Microcrystalline cellulose excipient control arm (capsule) All participants across all groups will receive standard care. Study endpoints will include the assessment of utility, toxicity, quality of life, and cosmesis, using various validated scales and scores. Ethics This study adheres to the principles outlined in the Helsinki Declaration (2024), the Nuremberg Code, and Mexico's General Health Law on health research. Given the wide therapeutic margin of the interventions, the study is classified as minimal risk. Statistical Analysis To evaluate the efficacy of the intervention (specifically, the change in the risk of dermatitis and fibrosis), we will calculate the hazard ratio using Cox regression and compare it with the Log-Rank test. Additionally, both fixed and random effects models will be performed and compared using the likelihood ratio test.
Interventions
OTHEREpicatechin
A comparison will be made between oral catechin (epicatechin) from two approaches: a preventive approach and a therapeutic approach.
A comparison will be made between topical catechin (EGCG) from two approaches: a preventive approach and a therapeutic approach.
A comparison will be made between oral placebo (microcrystalline cellulose) from two approaches: a preventive approach and a therapeutic approach.
OTHERSaline (0.9% NaCl)
A comparison will be made between topical placebo (0.9% saline solution) from two approaches: a preventive approach and a therapeutic approach.
Sponsors
Universidad de Guanajuato
Hospital Regional de Alta Especialidad del Bajio
CARLOS FRANCISCO SAAVEDRA GARCIA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histopathologically confirmed diagnosis of cancer. * Complete blood count, blood chemistry, and liver function tests within normal ranges. * Availability of an anatomopathological report. * Aged between 18 and 75 years. * Karnofsky performance status (KPS) score \> 60 or an Eastern Cooperative Oncology Group (ECOG) performance status score \< 3. * Candidate for radiotherapy with a prescribed dose of ≥40 Gy or its biological equivalent (EQD2). * Must provide written informed consent to participate in the study. * Must be able to swallow capsules. * Must meet one of the following cohort-specific criteria: 1. Prevention cohort: No clinical evidence of dermatitis at the initiation of radiotherapy. 2. Treatment cohort: Development of grade 1 dermatitis during radiotherapy, with symptom onset within the last 3 days.
Exclusion criteria
* Pregnant or lactating. * Immunocompromised or on chronic therapy with immunosuppressive or immunomodulatory medications. * History of chemical burns or unhealed wounds in the intended radiotherapy treatment area. * Current diagnosis of skin cancer or a known diagnosis of a DNA repair gene defect. * Prior radiotherapy to the area currently being treated. * Known allergy to any of the study compounds. * Currently receiving treatment with bortezomib, sunitinib, ticagrelor, or other antithrombotic agents. Withdrawal Criteria: * Adherence to the study intervention is less than 80%. * Withdrawal of consent. * Suspension of their radiotherapy sessions secondary to an acute infectious disease or the need for hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the radiation-induced skin reaction assessment scale (RISRAS) score | A baseline RISRAS scale evaluation is performed before the placebo or catechins treatment begins. Subsequent measurements are then taken up to week 7 during radiotherapy, and at 1 week and 2 weeks post-radiotherapy. | The Radiation-Induced Skin Reaction Assessment Scale (RISRAS) measures the severity of skin reactions to radiotherapy. It combines a clinician's assessment of visible signs with the patient's self-reported symptoms. A higher score, with a maximum of 37.5 points, indicates a more severe reaction. Clinicians apply the RISRAS scale to assess the the severity of acute radiation dermatitis. The change from baseline will be compared between the catechin and placebo groups to determine the impact on symptom severity. |
| Change in the incidence of chronic radiation fibrosis | A baseline RTOG scale evaluation is performed before the placebo or catechins treatment begins. Following treatment, primary measurements for fibrosis are taken during follow-up visits at 3 and 6 months post-radiotherapy. | Chronic radiation dermatitis/fibrosis This condition is defined as an adverse skin reaction that occurs more than 90 days after the start of radiotherapy. It involves permanent structural changes to the skin, such as fibrosis and vascular atrophy. Fibrosis can increase the risk of poor wound healing, skin contractures, and pain. Radiation therapy oncology group (RTOG) scale The RTOG scale is a standardized tool used to grade late-stage radiation effects. For the purposes of this study, the presence of fibrosis is graded on an ordinal scale with a minimum value of 0 and a maximum value of 2. On this scale, a higher score indicates a worse outcome (more severe fibrosis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dermatological Quality of Life | The measurement will be taken at baseline (before the placebo or catechins treatment begins), weekly up to week 7 during radiotherapy, and at 3 and 6 months post-radiotherapy. | Outcome Measure Description: The skin-related quality of life (QoL) will be determined and compared among patients in the different treatment groups. It will be evaluated using the Skindex-16 questionnaire, a validated 16-item tool that measures skin-specific QoL across three domains: symptoms, emotions, and functioning. The questionnaire has a minimum score of 0 and a maximum score of 100. On this scale, a higher score indicates a worse QoL. |
| Cumulative radiation dose at onset of grade ≥2 dermatitis | Measurements are taken throughout radiotherapy, up to week 7, with additional assessments at 1 and 2 weeks after the radiotherapy period. | The total radiation dose (in Gray - Gy) delivered to the skin at the precise moment the first clinical signs of grade 2 (or higher) radiation dermatitis are observed, as assessed by the radiation-induced skin reaction assessment scale (RISRAS). Interpretation: A higher cumulative dose (Gy) indicates a better outcome. It signifies greater radioprotection from the intervention, allowing the patient to tolerate more radiotherapy before experiencing significant skin toxicity. Unit of measure: Gray (Gy). |
| Duration of grade ≥2 dermatitis | Measurements are taken throughout radiotherapy, up to week 7, with additional assessments at 1 and 2 weeks after the radiotherapy period. | The length of time (in days) that the radiation dermatitis persists at a severity of Grade 2 or higher, from its onset until its resolution to grade 1 or lower, as measured by the radiation-induced skin reaction assessment scale (RISRAS). Interpretation: A shorter duration (fewer days) indicates a better outcome. It signifies a faster recovery and resolution of the skin adverse event, potentially improving patient quality of life and reducing treatment interruptions. Unit of measure: Days. |
| Percentage of Affected Skin Area by Radiation Dermatitis | Baseline, week 1, and week 3 of radiotherapy. | Standardized photographs of the irradiated area will be taken and analyzed using ImageJ® software to objectively quantify the percentage of skin affected by dermatitis. This objective measurement will be compared between the catechin and placebo groups. Unit of measure: Percentage (%). A higher percentage of affected skin indicates a more severe cutaneous reaction to radiation, while a lower percentage suggests a better clinical outcome and greater radioprotection. |
| Cosmetic Outcome | Photographs will be taken at three key points: Baseline, before the placebo or catechins treatment begins. During radiotherapy, specifically at weeks 1 and 3 of treatment. Post-radiotherapy, at both 3 and 6 months after treatment. | The cosmetic results of the skin in the treated area will be evaluated. This will be measured objectively using serial photographs. The photographs will be analyzed quantitatively with ImageJ software (National Institutes of Health, Bethesda, MD) to measure and compare changes in skin appearance (e.g., erythema, pigmentation, texture) between the catechin and placebo groups. Interpretation of results: Objective quantitative analysis: A statistically significant improvement in the quantitative skin appearance metrics (e.g., reduced erythema, improved homogeneity) in the catechin group compared to the placebo group at the post-radiotherapy time points indicates a better cosmetic outcome. A lack of significant difference or worse metrics in the catechin group would indicate no benefit or a worse outcome, respectively. |
| Incidence of Adverse Events | A baseline CTCAE v5.0 scale evaluation is performed before the placebo or catechins treatment begins. Subsequent evaluations are then conducted up to week 7 during radiotherapy and again at 3 months post-radiotherapy. | Outcome Measure Description: The frequency of adverse events, such as hepatic or hematological toxicity, will be quantified and compared between the catechin and placebo groups. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 will be used as the standardized system for grading the severity of acute adverse events. For this study, the events will be graded on its 5-point scale, ranging from a minimum of Grade 1 (mild) to a maximum of Grade 5 (death related to the adverse event). A higher score on this scale indicates a worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compare the efficacy of a topical epigallocatechin-3-gallate (EGCG) aerosol versus an oral epicatechin (Epi) capsule | The efficacy comparison of topical epigallocatechin gallate versus oral epicatechin will be conducted at the following times: at baseline (before administration), at week 7, 1 week post-radiotherapy, and 2 weeks post-radiotherapy. | The efficacy of topical versus oral administration routes will be compared using mixed-effects models to account for repeated measures and variability within subjects. Statistical Method: A Wald test will be applied to the coefficient of the administration route term in the mixed model to determine if there is a statistically significant difference in efficacy between the two treatment groups. Interpretation of results: A statistically significant Wald test result (p \< 0.05) for the administration route coefficient indicates a significant difference in efficacy between topical and oral treatments. The direction and magnitude of the coefficient will determine which route is superior. A non-significant result suggests no detectable difference in efficacy between the two administration routes. |
| Explore the 6-month event-free survival (EFS) of the study groups | 6 months after radiotherapy concludes. | Patient status is monitored throughout the study's follow-up period to determine the date of any event, defined as disease progression, cancer recurrence, or death from any cause. Statistical Method: EFS will be analyzed using Kaplan-Meier curves to visually compare the probability of remaining event-free between the study groups over the 6-month follow-up period. The log-rank test will be used to assess statistical significance. Interpretation of Results: A higher probability of event-free survival (i.e., a Kaplan-Meier curve that remains higher for longer) in the catechin group compared to the placebo group indicates a better clinical outcome. A statistically significant improvement (p \< 0.05) would suggest that the intervention reduces the risk of disease progression, recurrence, or death. |
Countries
Mexico
Outcome results
None listed