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
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 162
- 试验地点
- 2
- 主要终点
- Change in the incidence of chronic radiation fibrosis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 <
- •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.
排除标准
- •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
研究组 & 干预措施
Oral epicatechin prevention group
Oral epicatechin at a dose of 50 mg orally every 12 hours, starting from the start of radiotherapy, considering that one dose should be taken 2.5 hours before radiotherapy.
干预措施: Epicatechin (Other)
Topical epigallocatechin-3 gallate (EGCG) prevention group
EGCG 660 μmol/L solution will be applied 0.5mL/cm2, 3 times a day in the treatment area from the start of radiotherapy and up to 2 weeks after the end of radiotherapy.
干预措施: Epigallocatechin Gallate (EGCG) (Other)
Topical placebo prevention group
Application of 0.5 mL/cm2 of 0.9% saline solution to the treatment area, three times per day. This regimen should be followed from the onset of radiotherapy until two weeks post-radiotherapy.
干预措施: Saline (0.9% NaCl) (Other)
Oral epicatechin treatment group
Oral epicatechin at a dose of 50 mg orally every 12 hours from the development of grade 1 radiodermatitis, considering that one should be taken 2.5 hours before radiotherapy.
干预措施: Epicatechin (Other)
Oral placebo treatment group
Microcrystalline cellulose at a dose of 50 mg orally every 12 hours, starting from the development of grade 1 radiodermatitis, considering that a dose should be taken 2.5 hours before radiotherapy.
干预措施: Microcrystalline Cellulose NF (placebo) (Other)
Topical EGCG treatment group
A solution of epigallocatechin-3 gallate (EGCG) 660 μmol/L, 0.5 mL/cm2, will be applied 3 times a day to the area to be treated from the development of grade 1 radiodermatitis and up to 2 weeks after the end of radiotherapy.
干预措施: Epigallocatechin Gallate (EGCG) (Other)
Topical placebo treatment group
Application of 0.5 mL/cm2 of 0.9% saline solution to the treatment area, three times per day. This regimen should be followed from the development of grade 1 radiodermatitis until two weeks post-radiotherapy.
干预措施: Saline (0.9% NaCl) (Other)
Oral placebo prevention group
Microcrystalline cellulose at a dose of 50 mg orally every 12 hours, starting from the start of radiotherapy, considering that one dose should be taken 2.5 hours before radiotherapy.
干预措施: Microcrystalline Cellulose NF (placebo) (Other)
结局指标
主要结局
Change in the incidence of chronic radiation fibrosis
时间窗: 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).
Change in the radiation-induced skin reaction assessment scale (RISRAS) score
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- Percentage of Affected Skin Area by Radiation Dermatitis(Baseline, week 1, and week 3 of radiotherapy.)
研究者
CARLOS FRANCISCO SAAVEDRA GARCIA
Principal Investigator
Universidad de Guanajuato