Phase II Study to Evaluate the Effectiviness of Copaíba-based Mouthwash in Oral Mucotitis Prevention and Treatment in Oral Cancer Patients During Radioteraphy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Oral mucositis ulcers in tumoral area
研究概览
简要总结
Oral mucositis is the most significant acute toxicity of oral cavity radiotherapy. The available scientific evidence supports its preventive and therapeutic approach with low-level laser; however, this is unsuitable for tumor regions due to the risk of stimulating cellular metabolism. In this sense, an alternative treatment becomes necessary. Based on the preliminary results of the phase I study, a double-blind, randomized phase II study is suggested to evaluate the effectiveness of copaiba-based mouthwash in the prevention of oral mucositis in patients undergoing radiotherapy for oral cavity tumors. Patients will be randomized into 2 groups: A (copaíba) and B (placebo) and will use the mouthwash 4x/day. Each group will have 20 patients and be blind to the group in which they are included. They will be evaluated daily by a dental surgeon about oral mucositis, pain in the oral cavity and oropharynx, and dysphagia and will undergo daily laser therapy sessions, until the end of radiotherapy.
详细描述
Oral cavity cancer represents the 8th most common type in Brazil, with an estimated 15,100 new cases for each year of the 2023-2025 period. It depends on the patient's clinical condition, tumor location, and staging, involving surgery, chemotherapy (CT), or radiotherapy (RT), alone or in combination. RT involves doses between 50 and 70 Gy and, in addition to the action on the tumor, it produces toxicity in adjacent tissues, compromising the patient's quality of life.
Oral mucositis (OM) is the most significant acute toxicity related to RT associated or not with CT for tumors in this location.7,8 Its preventive and therapeutic approach has been proposed in several ways, but for RT of oral cavity tumors, it has There is evidence for the use of low-level laser therapy (LBP) and benzydamine hydrochloride. However, benzydamine hydrochloride is effective for those who received RT doses of up to 50 Gy, and the application of LBP in the tumor region is contraindicated as its effect is due to the activation of receptors of the respiratory chain, causing stimulation of cellular metabolism. Therefore, OM conditions tend to be severe in these locations, especially in patients with oral tumor lesions. In this sense, the need for an auxiliary treatment method becomes evident.
A phase I study with copaiba (CPB) in patients with oral cancer undergoing RT was previously developed by this group. In this case, the use of the mouthwash did not trigger dose-limiting toxicity in any of the treated patients, allowing us to conclude that the maximum tested dose of 15% used 4 times/day is safe for the development of a phase II study. None of the patients reported pain or burning related to the use of mouthwash in the absence of OM lesions, suggesting that it is safe and non-toxic for this use. The preliminary assessment of the effectiveness of the mouthwash showed the occurrence of OM lesions in 89.5% of patients, at most grade 3; None of the patients evaluated developed grade 4 mucositis lesions according to the WHO scale. None of the patients evaluated in the study needed to interrupt RT or QT due to OM injuries.
OBJECTIVES Main objective: to evaluate the effectiveness of copaiba-based mouthwash in preventing and treating oral mucositis in patients with oral cancer undergoing radiotherapy.
Secondary objectives: evaluate the safety of copaiba mouthwash in patients who use it; compare the incidence of oral mucositis in tumor and non-tumor areas in the two groups; compare the oral cavity pain index in the two groups; compare the oropharyngeal pain index in the two groups; compare the dysphagia index in the two groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will be blind to the group in which they are included, as will the study team. The non-blind team will be composed of the pharmacy team, that will be responsabli for the randomization and for dispensing of the investigational product/placebo.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 years or older;
- •Patients enrolled at INCA diagnosed with malignant neoplasms located in the oral cavity or oropharynx with an extension of the lesion to the oral cavity (IDC-10 C01 to C06 or IDC10); with the indication of exclusive RT (using the Intensity Modulated Radiotherapy (IMRT)/ Volumetric Modulated Arcotherapy (VMAT) technique) or combined with surgery and/or CT;
- •Patients with expected RT doses between 50 and 70Gy;
- •Patients capable of understanding and adhering to the protocol;
- •Patients capable of performing the oral hygiene protocol;
- •Patients who, after the information and instructions, can provide the free and informed consent form.
排除标准
- •Patients who are receiving drugs for the treatment and/or prevention of OM;
- •Patients undergoing RT with planning that excludes the oral cavity from the irradiation field;
- •Patients who report any allergy to CPB-based compounds.
研究组 & 干预措施
Copaíba
干预措施: Copaíba mouthwash (Drug)
Placebo
干预措施: Placebo mouthwash (Drug)
结局指标
主要结局
Oral mucositis ulcers in tumoral area
时间窗: From date of randomization until the date of first documented ulcer or date of last RT session/ mouthwash use day, whichever came first, assessed up to 7 weeks
To evaluate the incidence of oral mucositis (ulcers) in the tumor area in patients with oral cancer undergoing radiotherapy using copaiba-based mouthwash
次要结局
- Mouthwashs safety(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oral Mucositis (OMS)(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oral Mucositis ulcers (Sonis)(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oral Mucositis erithema (Sonis)(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oral Mucositis (Sonis)(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oral pain(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Oropharingeal pain(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Dysphagia(From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks)
- Siamoletry(At first RT day/ mouthwash use day, in the midle of the RT sessions/ mouthwash use and at last RT session/ mouthwash use day, assessed up to 7 weeks)
- Cytokines(At first RT day/ mouthwash use day, in the midle of the RT sessions/ mouthwash use and at last RT session/ mouthwash use day, assessed up to 7 weeks)
研究者
Heliton Spindola Antunes
PhD
Instituto Nacional de Cancer, Brazil