A Phase 2 interventional study of Copaíba mouthwash and Placebo mouthwash in Oral Mucositis, Oral Mucositis (Ulcerative) Due to Radiation and Oral Mucositis (Ulcerative) Due to Antineoplastic Therapy, sponsored by Instituto Nacional de Cancer, Brazil. Withdrawn at 2 sites in Brazil. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-09.
Sponsored by Instituto Nacional de Cancer, Brazil · Phase 2, Interventional, and Prevention
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.
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.
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Exclusion Criteria:
Drug: Copaíba mouthwash
Drug: Placebo mouthwash
A 15% aqueous solution of copaíba (Copaifera Officinalis Resin) manufactured by Interativo Farmácia de Manipulação will be used, under the formula of copaíba oil (Copaifera Officinalis Resin) 15%, liquid mint aroma 5%, tween 80 1%, aqueous solution (Distilled water + Nipagin 0.1%) qsp 100%. Patients will receive the solution once a week. They will be instructed to shake the bottle before use for homogenization, to use 10mL of the solution for each mouthwash (which should be measured in the 10mL measuring cup that comes with each bottle), 4 times a day, rinsing vigorously for 1 minute and discarding all the solution after use.
Placebo will be used, under the formula of liquid mint flavor 5%, Nipagim 0.1%, and distilled water qsp 60 ml, packed in packaging compatible with that of the product under investigation, maintaining the same physical characteristics to maintain blinding. The product will be stored at room temperature and stored in the INCA pharmacy. Patients will receive the solution once a week. They will be instructed to shake the bottle before use for homogenization, to use 10mL of the solution for each mouthwash (which should be measured in the 10mL measuring cup that comes with each bottle), 4 times a day, rinsing vigorously for 1 minute and discarding all the solution after use.
Oral mucositis ulcers in tumoral area
To evaluate the incidence of oral mucositis (ulcers) in the tumor area in patients with oral cancer undergoing radiotherapy using copaiba-based mouthwash
Time frame: 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
Mouthwashs safety
Assess the safety of copaiba mouthwash/placebo
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oral Mucositis (OMS)
Compare the incidence of maximum grade (grade 1, 2, 3, or 4 according to the WHO scale) of oral mucositis between the two groups
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oral Mucositis ulcers (Sonis)
Compare the average ulcerated area in the tumor area between the two groups according to the Sonis scale
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oral Mucositis erithema (Sonis)
Compare the average area with erythema in the tumor area between the two groups according to the Sonis scale
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oral Mucositis (Sonis)
Compare the average sum of the ulcerated area with the area of erythema in the tumor area between the two groups according to the Sonis scale
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oral pain
Compare the oral cavity pain index in the two groups according to the VAS and the CTCAE v5.0
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Oropharingeal pain
Compare the oropharyngeal pain index in the two groups according to the VAS and CTCAE v5.0
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Dysphagia
Compare the dysphagia index in the two groups according to CTCAE v5.0
Time frame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
Siamoletry
Compare unstimulated sialometry values in the two groups at the beginning, middle, and end of treatment
Time frame: 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
Compare the levels of pro-inflammatory cytokines IL-1 β, IL-6, and TNF- α in the two groups at the beginning, middle, and end of treatment
Time frame: 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
Plan to share: No
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Instituto Nacional de Cancer, Brazil