Clinical trial NCT02085460: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-03-12
Enrollment: 94
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

  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

Primary outcomes:
measure: 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.
timeFrame: 77 days
Secondary outcomes:
measure: Number of Subjects Who Did Not Developed Grade ≥3 Mucositis
timeFrame: Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 77
Other outcomes:
Locations:
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
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd.
name: Jun-ichi Hashimoto, PhD
role: STUDY_DIRECTOR
References:
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.
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.