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

Phase 2

Completed

• Conditions: Head and Neck Cancer
• Interventions: Drug: 2% Rebamipide liquid; Drug: Placebo; Drug: 4% Rebamipide liquid

• Registration Number: NCT02085460
• Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-11
• Study First Submitted QC: 2014-03-11
• Study First Posted: 2014-03-12
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Results First Submitted: 2021-03-11
• Results First Submitted QC: 2021-03-11
• Results First Posted: 2021-04-06
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-22
• Last Update Posted: 2021-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

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.

  1. Definitive therapy: nasopharynx, oropharynx, hypopharynx, or larynx
  2. 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:

  1. Neutrophil count: <1500 L
  2. Platelet count: <75000 L
  3. Hemoglobin: <10.0 g/L
  4. Aspartate aminotransferase (AST): >3 times the upper limit of the reference value at the trial site
  5. Alanine aminotransferase (ALT): >3 times the upper limit of the reference value at the trial site
  6. Serum bilirubin: >1.5 times the upper limit of the reference value at the trial site
  7. Serum albumin: <3.0 g/dL
  8. Serum creatinine: >1.5 the upper limit of the reference value at the trial site
  9. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2% Rebamipide liquid	2% Rebamipide liquid	6 times daily
Placebo	Placebo	6 times daily
4% Rebamipide liquid	4% Rebamipide liquid	6 times daily

Primary Outcome Measures

Name	Time	Method
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.	77 days	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

Secondary Outcome Measures

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