Efficacy and Safety of FORRAD® for the Management of Radiation-induced Mucositis in Patients With Nasopharyngeal Carcinoma Receiving IMRT

Study Overview
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Brief Summary
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Radiation therapy remains the principal treatment for nasopharyngeal carcinoma (NPC). The most frequently occurred radiation-related side effect is probably the radiation-induced oral mucositis (OM), which affects up to 100% of NPC patients receiving radiation therapy. When severe, oral mucositis increases the risk of infection and may compromise clinical outcomes by necessitating treatment breaks, dosage reductions, and reduced therapy compliance. In China, a quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine, is commonly prescribed when NPC patients begin to suffer from radiation-induced OM. However, the incidence of radiation-induced OM is still quite high. Oral Ulcer Gargle (FORRAD®) is a proprietary viscous liquid mucoadhesive hydrogel formulation. It creates a palliative barrier over injured mucosa, to prevent and to cure radiation-induced OM. The objective of this randomized phase II study is to assess the efficacy and safety of Oral Ulcer Gargle (FORRAD®) as an intervention for radiation-induced OM in the treatment of NPC, compared with the commonly used quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine.

Detailed Description
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Nasopharyngeal carcinoma (NPC) is one of the most common malignances in South China. Radiation therapy remains the principal treatment for NPC. The most frequently occurred radiation-related side effect is probably the radiation-induced oral mucositis (OM), which affects up to 100% of NPC patients receiving radiation therapy. Although intensity modulated radiation therapy (IMRT) has been widely used in China nowadays, the incidence of radiation-induced oral mucositis is still high. OM can decrease patients' oral intake and nutrition, leading to dehydration, weight loss, and declining performance status that may require intravenous fluid hydration, feeding tube placement, and hospitalization. OM also may increase opioid use. When severe, oral mucositis increases the risk of infection and may compromise clinical outcomes by necessitating treatment breaks, dosage reductions, and reduced therapy compliance. Common clinical management strategies include bland rinses, topical anesthetics and analgesics, mucosal coating agents, and systemic analgesics. However, none of these interventions has been supported by conclusive evidence. In China, a quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine, is commonly prescribed when NPC patients begin to suffer from radiation-induced OM. Oral Ulcer Gargle (FORRAD®) is a proprietary viscous liquid mucoadhesive hydrogel formulation. It creates a palliative barrier over injured mucosa, to prevent and to cure radiation-induced OM. The objective of this randomized phase II study is to assess the efficacy and safety of Oral Ulcer Gargle (FORRAD®) as an intervention for radiation-induced OM in the treatment of NPC, compared with the commonly used quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine.

Official Title
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Efficacy and Safety of FORRAD® for the Management of Radiation-induced Mucositis in Patients With Nasopharyngeal Carcinoma Receiving IMRT: A Single-center, Randomized Controlled Trial

Conditions
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Nasopharyngeal Neoplasms, Stomatitis

Intervention / Treatment
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* Drug: Oral Ulcer Gargle (FORRAD®)
* Drug: Quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed and previously untreated nasopharyngeal carcinoma. Age ≥ 18 years and ≤ 65 years. Karnofsky performance status (KPS) score ≥ 70. Planned to receive radiotherapy alone or concurrent chemoradiotherapy, with intensity-modulated radiation therapy (IMRT). Adequate bone marrow function: while blood cell >= 3,000/μL, absolute neutrophil count >= 1,500/μL, hemoglobin >= 100g/L, platelet >= 75,000/μL. Life expectancy of >= 3 months. Exclusion Criteria: Known allergic reaction to any component of Oral Ulcer Gargle (FORRAD®) or quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine, or severe allergic constitution. Other conditions that the investigators consider as inappropriate for enrolling into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FORRAD group<br>This group of patients will receive Oral Ulcer Gargle (FORRAD®) during study for prevention and treatment of acute radiation-induced oral mucositis (OM). This is the experimental group. | Drug: Oral Ulcer Gargle (FORRAD®)<br>* Oral Ulcer Gargle (FORRAD®) is prescribed at the beginning of radiotherapy for free. Patients are asked to start application of Oral Ulcer Gargle (FORRAD®) at the onset of radiotherapy, four times a day (after meals and before bedtime), until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation-induced oral mucositis. When grade > 3 OM happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted.<br>|
| Active Comparator: Quadruple mixture group<br>This group of patients will receive quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine, during study for prevention and treatment of acute radiation-induced oral mucositis (OM). This is the active comparator group. | Drug: Quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine<br>* Quadruple mixture is prescribed at the beginning of radiotherapy. Patients are asked to start application of quadruple mixture at the onset of radiotherapy, four times a day (before meals and before bedtime), until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation-induced oral mucositis. When grade > 3 OM happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade ≥ 3 mucositis | Incidence of grade ≥ 3 mucositis according to CTCAE version 4.0 | Day 56 after completion or termination of radiotherapy | 
| OMAS | Oral Mucositis Assessment Scale (OMAS) provides an objective assessment of oral mucositis based on assessment of the appearance and extent of redness and ulceration in various areas of the mouth. | Day 56 after completion or termination of radiotherapy | 
| OMDQ MTS question 2 (Q2) score | Oral Mucositis Daily Questionnaire (OMDQ) mouth and throat soreness (MTS) question 2 (Q2) is a 5-point categorical scale in which patients grade MTS from 0 (no soreness) to 4 (extreme soreness)3 which is a component of the OMDQ in that it tracks very well with objective (WHO score and opioid use) and subjective measurement of OM severity. | Day 56 after completion or termination of radiotherapy | 
| WHO score | The World Health Organization (WHO) Oral Toxicity score combines both elements into a single score that grades the severity of the condition from 0 (no oral mucositis) to 4 (swallowing not possible such that patient needs supplementary nutrition). | Day 56 after completion or termination of radiotherapy | 
| EORTC QLQ-C30 | EORTC QLQ-C30 is a Quality-of-Life Instrument proposed by the European Organization for Research and Treatment of Cancer (EORTC), for use in International Clinical Trials in Oncology. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. | Day 56 after completion or termination of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interruption time during the schedule of radiotherapy | The cumulative interruption time during the schedule of radiotherapy because of grade 4 or higher radiation-induced oral mucositis. | Through radiotherapy completion or termination, an average of 7 weeks | 
| Time for healing of radiation-induced oral mucositis | Time until healing of radiation-induced oral mucositis, after the completion or the termination of radiotherapy. | Through study completion, an average of 15 weeks | 
| The cumulative dose of opioid used | The cumulative dose of opioid used from the beginning of radiotherapy until the completion of study. | Through study completion, an average of 15 weeks | 
| The cumulative time using opioid | The cumulative time using opioid from the beginning of radiotherapy until the completion of study. | Through study completion, an average of 15 weeks | 
| The change of body weight from baseline. | The change of body weight before radiotherapy and the day when radiotherapy is completed or terminated. | Baseline and 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma (NPC), radiotherapy, oral mucositis (OM)