Prevention of Radiation-induced Severe Oral Mucositis in Oral Cavity, Oropharynx, Hypopharynx, and Cavum Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the benefit of a mouthwash with a phytopharmaceutical preparation, Homeodent®, compared to a mouthwash solution containing sodium bicarbonate, for prevention of severe mucositis (grade ≥3, RTOG classification) in patients receiving irradiation for oral cavity, oropharynx, hypopharynx or cavum cancer. This is a phase III, controlled, randomized, single blind study. The estimated inclusion period is approximately 24 months. The number of patients required in this monocentric study is 330 (165 per arm).

Detailed Description
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The standard treatment of oral cavity, oropharynx, hypopharynx, and cavum cancers is external radiotherapy. However, one of the associated toxicities is the occurrence of mucositis which can be a limiting factor in the treatment (dose reduction or treatment interruption can limit patient's survival), patient's quality of life decreases and severe complications can occur. The treatment of mucositis is mainly symptomatic; a randomized study has shown a benefit of a mouthwash with Benzydamine, a non steroidal anti-inflammatory drug, for patients receiving 50-Gy radiation. Another study with a lower number of patients has also shown a benefit of using a zinc sulfate solution. Boiron laboratories have developed a phytopharmaceutical preparation, Homeodent®, which has no secondary effects and which could prevent radiation-induced mucositis. This study will evaluate the efficiency of mouthwash with Homeodent® in a large randomized trial.

Official Title
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Randomized Evaluation of a Phytopharmaceutical in Prevention of Severe Oral Mucositis in Patients Receiving Radiotherapy for Oral Cavity, Oropharynx, Hypopharynx, or Cavum Cancer

Conditions
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Oropharynx Cancer, Hypopharynx Cancer

Intervention / Treatment
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* Drug: Homeodent®
* Drug: 1.4% Sodium Bicarbonate solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient aged ≥ 18 years ECOG PS ≤ 2 Patient with oral cavity and/or oropharynx and/or hypopharynx and/or cavum epidermoid carcinoma, whatever the stage Patient receiving a minimum radiation dose of 60 Gy Planned radiotherapy to at least 1/3 of the oral mucosa and/or oropharynx Mandatory affiliation with a health insurance system Signed, written informed consent Exclusion Criteria: Previous irradiation to the oral mucosa and/or oropharynx Pre-existing mucositis Pregnant or lactating woman (negative serum or urinary pregnancy test for women with child-bearing potential) Patient included in another study including experimental radiotherapy possibly toxic to the mucosa difficult follow up of the patient patient deprived of civil rights

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Homeodent®<br>Mouthwash with Homeodent® is started on the first day of irradiation, then continued until the end of the irradiation period or until occurrence of grade ≥3 mucositis. In case of grade ≥3 mucositis, patients are instructed to mouthwash with Sodium Bicarbonate solution until complete disappearance of mucositis or until the end of irradiation. | Drug: Homeodent®<br>* Two-minute mouthwash with 5 ml of solution diluted in 125 ml of water, 3 times per day after meals and tooth brushing.<br>|
| Active Comparator: 1.4 % Sodium Bicarbonate solution<br>Mouthwash with sodium bicarbonate is started on the first day of irradiation, then continued until the end of the irradiation period. In case of grade ≥3 mucositis, mouthwash is continued until complete disappearance of the mucositis or until the end of irradiation. In both arms, after the end of irradiation, patients can receive treatment with Sodium Bicarbonate solution until complete disappearance of the mucositis. | Drug: 1.4% Sodium Bicarbonate solution<br>* Two-minute mouthwash with 125 ml of solution, 3 times per day after meals and tooth brushing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of occurrence of grade ≥ 3 (RTOG classification) mucositis during irradiation (only the first occurrence will be reported) |  | At the end of irradiation period (6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of grade ≥2 mucositis |  | At the end of irradiation period (6 weeks) | 
| Rate of Mycosis and Herpes virus infection |  | At the end of irradiation period (6 weeks) | 
| Rate of use of symptomatic treatment in case of occurrence of mucositis |  | At the end of irradiation period (6 weeks) | 
| Rate and duration of radiation treatment interruption for toxicity |  | At the end of irradiation period (6 weeks) | 
| radiation dose, duration of grade ≥3 mucositis, maximum weight loss and maximum level of oral pain in case of grade ≥3 mucositis. |  | during the occurence of grade≥3 mucositis | 
| Treatment tolerance assessed through a satisfaction questionnaire, and evaluation of compliance |  | during medication administration | 
| Nutritional intake, estimated using caloric intake and the Detsky score, and rate of enteral and/or parenteral nutrition, in case of toxicity during irradiation |  | during the period of toxicity | 
| Rate of agreement between the radiation oncologist and the stomatologist for the detection of Grade ≥2 (RTOG classification) mucositis |  | At the end of irradiation period (6 weeks) | 
| Evaluation of the cost of severe mucositis treatment |  | during and until the end of severe mucositis treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidermoid carcinoma, Hypopharynx, Oropharynx, Oral cavity, Oral mucosa, Cavum, Severe Oral mucositis, Radiotherapy, Phytotherapy