Oral or Topical Catechins for Radiation Dermatitis

Official title

Efficacy of Oral or Topical Catechins vs. Placebo as an Adjuvant for the Prevention and Management of Radiation Dermatitis in Oncology Patients: a Randomized Trial

Overview

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

• Other Epicatechin
  A comparison will be made between oral catechin (epicatechin) from two approaches: a preventive approach and a therapeutic approach.
• Other Epigallocatechin Gallate (EGCG)
  A comparison will be made between topical catechin (EGCG) from two approaches: a preventive approach and a therapeutic approach.
• Other Microcrystalline Cellulose NF (placebo)
  A comparison will be made between oral placebo (microcrystalline cellulose) from two approaches: a preventive approach and a therapeutic approach.
• Other Saline (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.

Primary outcome measures

• Change in the incidence of chronic radiation fibrosis [Time frame: 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.]
• Change in the radiation-induced skin reaction assessment scale (RISRAS) score [Time frame: 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.]

Secondary outcome measures (6)

• Incidence of Adverse Events [Time frame: 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.]
• Dermatological Quality of Life [Time frame: 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.]
• Cumulative radiation dose at onset of grade ≥2 dermatitis [Time frame: Measurements are taken throughout radiotherapy, up to week 7, with additional assessments at 1 and 2 weeks after the radiotherapy period.]
• Cosmetic Outcome [Time frame: 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.]
• Duration of grade ≥2 dermatitis [Time frame: Measurements are taken throughout radiotherapy, up to week 7, with additional assessments at 1 and 2 weeks after the radiotherapy period.]
• Percentage of Affected Skin Area by Radiation Dermatitis [Time frame: Baseline, week 1, and week 3 of radiotherapy.]

Eligibility criteria

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:

• Prevention cohort: No clinical evidence of dermatitis at the initiation of radiotherapy.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Mexico · 1 center

• HRAEB — León

Publications

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• Moreno-Ulloa A , Najera-Garcia N , Hernandez M , Ramirez-Sanchez I , Taub PR , Su Y , Beltran-Partida E , Ceballos G , Dugar S , Schreiner G , Best BM , Ciaraldi TP , Henry RR , Villarreal F . A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of (+)-epicatechin on cardiometabolic endpoints. Food Funct. 2018 Jan 24;9(1):307-319. doi: 10.1039/c7fo01028a. PMID 29171848
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• World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025 Jan 7;333(1):71-74. doi: 10.1001/jama.2024.21972. PMID 39425955
• Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegried NL, Staniszewska S, Taylor RS, Th PMID 40228477
• Wooding H, Yan J, Yuan L, Chyou TY, Gao S, Ward I, Herst PM. The effect of Mepitel Film on acute radiation-induced skin reactions in head and neck cancer patients: a feasibility study. Br J Radiol. 2018 Jan;91(1081):20170298. doi: 10.1259/bjr.20170298. Epub 2017 Nov 8. PMID 29072852
• Robijns J, Censabella S, Claes S, Pannekoeke L, Busse L, Colson D, Kaminski I, Bulens P, Maes A, Noe L, Brosens M, Timmermans A, Lambrichts I, Somers V, Mebis J. Prevention of acute radiodermatitis by photobiomodulation: A randomized, placebo-controlled trial in breast cancer patients (TRANSDERMIS trial). Lasers Surg Med. 2018 Feb 10. doi: 10.1002/lsm.22804. Online ahead of print. PMID 29427390

Identifiers

NCT: NCT07149506 · CEI-038-2025 · CI/HRAEB/024/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗