Copaíba-based Mouthwash in Oral Mucotitis Prevention and Treatment in Oral Cancer Patients During Radioteraphy

Phase 2

Recruiting

• Conditions: Oral Mucositis; Oral Mucositis (Ulcerative) Due to Radiation; Oral Mucositis (Ulcerative) Due to Antineoplastic Therapy; Oral Mucositis Due to Radiation
• Interventions: Drug: Copaíba mouthwash; Drug: Placebo mouthwash

• Registration Number: NCT06708702
• Lead Sponsor: Instituto Nacional de Cancer, Brazil

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-11-05
• Study First Submitted QC: 2024-11-26
• Study First Posted: 2024-11-27
• Study Start: 2025-01-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-11
• Primary Completion: 2027-07
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Copaíba	Copaíba mouthwash	-
Placebo	Placebo mouthwash	-

Primary Outcome Measures

Name	Time	Method
Oral mucositis ulcers in tumoral area	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

Secondary Outcome Measures

Name	Time	Method
Oral Mucositis erithema (Sonis)	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the average area with erythema in the tumor area between the two groups according to the Sonis scale
Oral Mucositis (Sonis)	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	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
Mouthwashs safety	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Assess the safety of copaiba mouthwash/placebo
Oral Mucositis (OMS)	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the incidence of maximum grade (grade 1, 2, 3, or 4 according to the WHO scale) of oral mucositis between the two groups
Oral Mucositis ulcers (Sonis)	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the average ulcerated area in the tumor area between the two groups according to the Sonis scale
Oral pain	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the oral cavity pain index in the two groups according to the VAS and the CTCAE v5.0
Oropharingeal pain	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the oropharyngeal pain index in the two groups according to the VAS and CTCAE v5.0
Dysphagia	From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks	Compare the dysphagia index in the two groups according to CTCAE v5.0
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	Compare unstimulated sialometry values in the two groups at the beginning, middle, and end of treatment
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	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

Trial Locations

Locations (2)

Instituto Nacional de Cancer, Brazil; 🇧🇷 Rio de Janeiro, Brazil

Instituto Nacional de Cancer; 🇧🇷 Rio de Janeiro, Brazil