CompletedNCT02085460Updated Oct 18, 2021Results posted

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

A Phase 2 interventional study of Placebo and 2% Rebamipide liquid in Head and Neck Cancer, sponsored by Otsuka Pharmaceutical Co., Ltd.. Completed at 5 sites in Japan. Open to participants aged 20 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-10-18.

Sponsored by Otsuka Pharmaceutical Co., Ltd. · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 94
Allocation: Randomized
Ages: 20 Years to 75 Years
Sex: All

Study 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.

Conditions studied

Head and Neck Cancer

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In context

Head and Neck Neoplasms

2,344 studies on the registry are indexed under Head and Neck Neoplasms; 551 are open to participants now.

This study's enrollment of 94 is above the median of 47 across 1,751 interventional studies indexed under Head and Neck Neoplasms.

Browse Head and Neck Neoplasms studies →

Lead sponsor

Otsuka Pharmaceutical Co., Ltd. is the lead sponsor of 140 studies on the registry; 11 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 20 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 94 participants (actual)

Study arms

Placebo comparator
Placebo
6 times daily
Drug: Placebo
Experimental
2% Rebamipide liquid
6 times daily
Drug: 2% Rebamipide liquid
Experimental
4% Rebamipide liquid
6 times daily
Drug: 4% Rebamipide liquid

Interventions

DrugPlacebo
Drug2% Rebamipide liquid
Drug4% Rebamipide liquid

What researchers measure

Primary outcomes

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
Time frame: 77 days

Secondary outcomes

Number of Subjects Who Did Not Developed Grade ≥3 Mucositis
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

Results

Posted Apr 6, 2021

Participant flow

Participant flow — Overall Study
Milestone	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo
Started	31	32	31
Completed	17	24	21
Not completed	14	8	10
Withdrew: Adverse event	2	2	1
Withdrew: Physician decision	1	1	2
Withdrew: Withdrawal by subject	11	5	7

Outcome measures

PrimaryIncidence 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

Time frame:: 77 days
Reported as:: Number · percentage of participants

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.
percentage of participants	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo
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.	29.0	25.0	38.7

SecondaryNumber of Subjects Who Did Not Developed Grade ≥3 Mucositis

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
Reported as:: Number · participants

Number of Subjects Who Did Not Developed Grade ≥3 Mucositis
participants	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo
Day 1	31	31	31
Day 8	29	31	30
Day 15	27	30	29
Day 22	25	29	23
Day 29	23	25	23
Day 36	20	20	19
Day 43	18	18	16
Day 50	17	18	15
Day 57	12	16	13
Day 64	11	15	11
Day 71	8	13	8
Day 77	6	11	8

Adverse events

Collected over Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
2% Rebamipide Liquid	0/31 (0%)	5/31 (16.1%)	31/31 (100%)
4% Rebamipide Liquid	0/32 (0%)	5/32 (15.6%)	32/32 (100%)
Placebo	0/31 (0%)	4/31 (12.9%)	31/31 (100%)

Most frequent serious events

Showing 10 of 11

Most frequent serious events
Event	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders	1/31	3/32	0/31
Sinus node dysfunctionCardiac disorders	1/31	0/32	0/31
DysphagiaGastrointestinal disorders	1/31	0/32	0/31
NauseaGastrointestinal disorders	0/31	0/32	1/31
Hepatic function abnormalHepatobiliary disorders	0/31	0/32	1/31
Alanine aminotransferase increasedInvestigations	1/31	0/32	0/31
Subarachnoid haemorrhageNervous system disorders	0/31	0/32	1/31
Acute kidney injuryRenal and urinary disorders	0/31	1/32	1/31
Renal impairmentRenal and urinary disorders	1/31	0/32	0/31
Blood creatinine increasedInvestigations	0/31	1/32	0/31

Most frequent other events

Showing 10 of 79

Most frequent other events
Event	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo
StomatitisGastrointestinal disorders	27/31	30/32	30/31
Radiation skin injuryInjury, poisoning and procedural complications	22/31	26/32	20/31
DysgeusiaNervous system disorders	22/31	26/32	25/31
NauseaGastrointestinal disorders	25/31	24/32	25/31
ConstipationGastrointestinal disorders	21/31	25/32	24/31
Dry mouthGastrointestinal disorders	20/31	24/32	19/31
Decreased appetiteMetabolism and nutrition disorders	21/31	22/32	23/31
Weight decreasedInvestigations	15/31	12/32	18/31
HiccupsRespiratory, thoracic and mediastinal disorders	11/31	15/32	10/31
MalaiseGeneral disorders	14/31	12/32	14/31

Baseline characteristics

Full analysis set comprised patients who received the study drug or placebo at least once and whose efficacy data were collected immediately after beginning the treatment.

Age, Categorical
Age, Categorical(Participants)	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo	Total
<=18 years	0	0	0	0
Between 18 and 65 years	17	19	19	55
>=65 years	14	13	12	39

Sex: Female, Male
Sex: Female, Male(Participants)	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo	Total
Female	5	6	6	17
Male	26	26	25	77

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo	Total
Asian	31	32	31	94

Region of Enrollment
Region of Enrollment(Participants)	2% Rebamipide Liquid	4% Rebamipide Liquid	Placebo	Total
Japan	31	32	31	94

Study locations

5 sites

Chubu Region, Japan
Chugoku Region, Japan
Kanto Region, Japan
Kinki Region, Japan
Tohoku Region, Japan

References and documents

Publications

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. PubMed 30426268 ↗
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. PubMed 28476132 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 18, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02085460
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Responsible party: Sponsor
First posted: Mar 12, 2014
Start date: Mar 2014
Primary completion: Aug 2015
Completion: Aug 2015
Results posted: Apr 6, 2021
Last update: Oct 18, 2021

Study contacts

Jun-ichi Hashimoto, PhD

study director · Otsuka Pharmaceutical Co., Ltd.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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