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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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Placebo
2% Rebamipide liquid
4% Rebamipide liquid
Sponsored by
Otsuka Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

2% Rebamipide liquid

4% Rebamipide liquid

Arm Description

6 times daily

6 times daily

6 times daily

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Number of Subjects Who Did Not Developed Grade ≥3 Mucositis
Day 1 was defined as the start of chemotherapy.

Full Information

First Posted
March 11, 2014
Last Updated
September 22, 2021
Sponsor
Otsuka Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02085460
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
6 times daily
Arm Title
2% Rebamipide liquid
Arm Type
Experimental
Arm Description
6 times daily
Arm Title
4% Rebamipide liquid
Arm Type
Experimental
Arm Description
6 times daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
2% Rebamipide liquid
Intervention Type
Drug
Intervention Name(s)
4% Rebamipide liquid
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
77 days
Secondary Outcome Measure Information:
Title
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis
Description
Day 1 was defined as the start of chemotherapy.
Time Frame
Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 77

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun-ichi Hashimoto, PhD
Organizational Affiliation
Otsuka Pharmaceutical Co., Ltd.
Official's Role
Study Director
Facility Information:
City
Chubu Region
Country
Japan
City
Chugoku Region
Country
Japan
City
Kanto Region
Country
Japan
City
Kinki Region
Country
Japan
City
Tohoku Region
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
30426268
Citation
Ueno T, Zenda S, Konishi T, Yurikusa T, Shibasaki Y, Nagamoto H, Fujii M. The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer. Int J Clin Oncol. 2019 Mar;24(3):241-247. doi: 10.1007/s10147-018-1355-7. Epub 2018 Nov 13.
Results Reference
background
PubMed Identifier
28476132
Citation
Yokota T, Ogawa T, Takahashi S, Okami K, Fujii T, Tanaka K, Iwae S, Ota I, Ueda T, Monden N, Matsuura K, Kojima H, Ueda S, Sasaki K, Fujimoto Y, Hasegawa Y, Beppu T, Nishimori H, Hirano S, Naka Y, Matsushima Y, Fujii M, Tahara M. Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study. BMC Cancer. 2017 May 5;17(1):314. doi: 10.1186/s12885-017-3295-4.
Results Reference
derived

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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

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