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

• ClinicalTrials.gov Identifier: NCT02085460
• Recruitment Status: Completed
• First Posted: March 12, 2014
• Results First Posted: April 6, 2021
• Last Update Posted: October 18, 2021
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: March 11, 2014
• First Posted Date: March 12, 2014
• Results First Submitted Date: March 11, 2021
• Results First Posted Date: April 6, 2021
• Last Update Posted Date: October 18, 2021
• Study Start Date: March 2014
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2021)

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. [ Time Frame: 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

• Original Primary Outcome Measures (submitted: March 11, 2014): Incidence of oral mucositis graded as severe or worse. [ Time Frame: 77 days ]

Current Secondary Outcome Measures (submitted: March 11, 2021)

Number of Subjects Who Did Not Developed Grade ≥3 Mucositis [ Time Frame: Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 77 ]

Day 1 was defined as the start of chemotherapy.

Original Secondary Outcome Measures (submitted: March 11, 2014)

• Onset time, duration and incidence of oral mucositis. [ Time Frame: 77 days ]
• The maximum severity grade for oral mucositis. [ Time Frame: 77 days ]
• Quality of life [ Time Frame: 77 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Head and Neck Cancer

Intervention

• Drug: Placebo
• Drug: 2% Rebamipide liquid
• Drug: 4% Rebamipide liquid

Study Arms

• Placebo Comparator: Placebo
  6 times daily
  Intervention: Drug: Placebo
• Experimental: 2% Rebamipide liquid
  6 times daily
  Intervention: Drug: 2% Rebamipide liquid
• Experimental: 4% Rebamipide liquid
  6 times daily
  Intervention: Drug: 4% Rebamipide liquid

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 28, 2016): 94
• Original Estimated Enrollment (submitted: March 11, 2014): 90
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02085460
• Other Study ID Numbers: 037-12-001; JapicCTI-142467 ( Other Identifier: Japic )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jun-ichi Hashimoto, PhD; Otsuka Pharmaceutical Co., Ltd.

• PRS Account: Otsuka Pharmaceutical Co., Ltd.
• Verification Date: September 2021