Clinical trial NCT06708702: Copaíba-based Mouthwash in Oral Mucotitis Prevention and Treatment in Oral Cancer Patients During Radioteraphy
Official title: Phase II Study to Evaluate the Effectiviness of copaíba-based Mouthwash in Oral Mucotitis Prevention and Treatment in Oral Cancer Patients During Radioteraphy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oral Mucositis
Oral Mucositis (Ulcerative) Due to Radiation
Oral Mucositis (Ulcerative) Due to Antineoplastic Therapy
Oral Mucositis Due to Radiation
Keywords: oral mucositis
radiotheraphy
copaiba
low power laser theraphy
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
First posted: 2024-11-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase II, randomized, placebo-controlled, double-blind study in a single institution, to evaluate the effectiveness of copaiba-based mouthwash in preventing oral mucositis in the tumor area in patients with oral cancer undergoing RT alone or in combination with CT. The participant will be randomized 1:1 to the study groups in a stratified manner according to the oncological treatments to which the patient will be subjected, according to the groups: exclusive treatment with RT and treatment with RT associated with CT. Randomization will be carried out using the REDCap® program by a non-blinded pharmacist, trained for this role.

Participants\&#39; daily care (outcome assessment) will begin on the first day of RT, and continue until the end of it, regardless of whether the patient has already reached the study\&#39;s primary outcome or not.
Primary purpose: PREVENTION

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\&#39;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\&#39;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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oral mucositis ulcers in tumoral area
timeFrame: 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
Secondary outcomes:
measure: Mouthwashs safety
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oral Mucositis (OMS)
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oral Mucositis ulcers (Sonis)
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oral Mucositis erithema (Sonis)
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oral Mucositis (Sonis)
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oral pain
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Oropharingeal pain
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Dysphagia
timeFrame: From date of randomization until the date of last RT session/ mouthwash use day, assessed up to 7 weeks
measure: Siamoletry
timeFrame: 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
measure: Cytokines
timeFrame: 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
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer, Brazil
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
Study officials:
References: