A Phase 2 Trial of Rebamipide Liquid to Determine the Effective Dose for Prevention of Chemoradiotherapy-induced Oral Mucositis in Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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To investigate the efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer following administration of rebamipide and to determine the optimal dose of rebamipide.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 2 Trial of Rebamipide Liquid to Determine the Effective Dose for Prevention of Chemoradiotherapy-induced Oral Mucositis in Patients With Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: 2% Rebamipide liquid
* Drug: 4% Rebamipide liquid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Head and neck cancer patients scheduled for definitive or postoperative chemoradiotherapy. Patients with a histopathological diagnosis of head and neck cancer and primary tumor in one of the following regions. Definitive therapy: nasopharynx, oropharynx, hypopharynx, or larynx Postoperative therapy: oral cavity, oropharynx, hypopharynx, or larynx Patients with no history of chemotherapy, radiotherapy, or chemoradiotherapy for head and neck cancer Patients with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Patients who are able to hold fluid in the mouth Patients who are able to swallow the investigational medicinal product (IMP) Patients expected to survive for at least 3 months Patients who have given written informed consent in person Patients who can stay at or visit the hospital for scheduled examinations and observations Patients who are able to take contraceptive measures to avoid pregnancy of the patient or their partner from the time of informed consent until 4 weeks after completion of IMP administration Exclusion Criteria: Patients with primary malignant tumors other than head and neck cancer. Patients with symptomatic viral, bacterial, or fungal infection Patients with serious renal impairment Patients with distant metastasis Patients with severe complications (uncontrolled cardiac disease, diabetes, hypertension, etc) Patients with any of the following laboratory test results: Neutrophil count: <1500 L Platelet count: <75000 L Hemoglobin: <10.0 g/L Aspartate aminotransferase (AST): >3 times the upper limit of the reference value at the trial site Alanine aminotransferase (ALT): >3 times the upper limit of the reference value at the trial site Serum bilirubin: >1.5 times the upper limit of the reference value at the trial site Serum albumin: <3.0 g/dL Serum creatinine: >1.5 the upper limit of the reference value at the trial site Creatinine clearance : <30 mL/min Patients complicated with autoimmune disease Patients requiring continuous systemic administration of glucocorticoid Female patients who are pregnant or lactating, who may possibly be pregnant, or who wish to become pregnant Patients who have participated in any other clinical trial within 4 weeks prior to initiation of chemoradiotherapy Patients who have a history of drug allergy to rebamipide, cisplatin, or other platinum compounds Patients who are otherwise judged by the investigator or sub-investigator to be inappropriate for inclusion in the trial

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>6 times daily | Drug: Placebo<br> <br> |
| Experimental: 2% Rebamipide liquid<br>6 times daily | Drug: 2% Rebamipide liquid<br> <br> |
| Experimental: 4% Rebamipide liquid<br>6 times daily | Drug: 4% Rebamipide liquid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade ≥3 Oral Mucositis Determined by Clinical Examination and Assessed by Central Review According to the Common Terminology Criteria of Adverse Events (CTCAE) Version 3.0. | Investigators who had undergone specific training assessed the severity of oral mucositis twice every week. To evaluate the severity of oral mucositis objectively, the clinical findings of the oral mucosa as well as functional disorders and symptomatic aspects were recorded in the Oral Mucositis Assessment Sheet by each investigator. Photographic documentation of the oral mucosa was also submitted by each investigator, 3 days before or 57 days after initiation of chemoradiotherapy, or at the time of withdrawal. The Oral Mucositis Assessment Sheets and photographic documentation were then reviewed by the Oral Mucositis Evaluation Committee to grade the severity of oral mucositis according to the CTCAE 3.0.z | 77 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Did Not Developed Grade ≥3 Mucositis | Day 1 was defined as the start of chemotherapy. | Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 77 |