A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancer

STUDY PROTOCOL A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancer Kazuhiro Omori 1*, Kohei Furukawa2, Masatoshi Usubuchi3¤, Tomofumi Hamada4, Tadahiko Shien5, Michihiro Yoshida6, Yuki Nakatsuka 6, Katsuyuki Hotta 6, Soichiro Ibaragi 7, Shogo Takashiba 1 1 Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan, 2 Department of Dentistry and Oral Surgery, Shikoku Cancer Center, Ehime, Japan, 3 Department of Dentistry, Miyagi Cancer Center, Miyagi, Japan, 4 Department of Dentistry and Oral Surgery, Sagara Hospital, Kagoshima, Japan, 5 Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan, 6 Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan, 7 Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan ¤ Current Address: Department of Dentistry and Oral Surgery, Hakodate Medical Center, Hokkaido, Japan * OPEN ACCESS Citation: Omori K, Furukawa K, Usubuchi M, Hamada T, Shien T, Yoshida M, et al. (2026) A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancer. PLoS One 21(6): e0350803. https://doi.org/10.1371/journal.pone.0350803 Editor: Yu Uneno, Kyoto University Hospital, JAPAN Received: November 24, 2025 Accepted: May 14, 2026 Published: June 4, 2026 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal. pone.0350803 Copyright: © 2026 Omori et al. This is an open access article distributed under the terms of Abstract Oral mucositis is a frequent and debilitating adverse event observed in patients undergoing chemotherapy or radiotherapy. Current management strategies are limited in duration, require frequent application, and fail to address the mechanical irritation from teeth. A novel device, Soft Protector CPC, was developed to overcome these limitations. This multicenter, randomized, two-arm, open-label, confirmatory trial aims to evaluate the efficacy and safety of Soft Protector CPC in patients with breast cancer undergoing chemotherapy. A total of 154 participants will be randomly assigned in a 1:1 ratio to receive either oral care with Soft Protector CPC or oral care alone. The primary endpoint will be oral mucositis as assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 during the comparative treatment period. The secondary endpoints will include CTCAE v3.0 during the continuous treatment period, oral mucositis, pain (CTCAE v5.0), quality of life (Patient Reported Outcomes-CTCAE version 1.0 [PRO-CTCAE v1.0], the 15-item oral health questionnaire of the European Organization For Research And Treatment Of Cancer [EORTC QLQ-OH15], and the pain Numeric Rating Scale), onset and site of mucositis, completion of chemotherapy, use of rescue medications, technical feasibility, and patient preference. The safety endpoints will include adverse events, device malfunction, and laboratory tests. This trial is expected to establish the clinical utility of the Soft Protector CPC for the prevention and management of oral mucositis, PLOS One | https://doi.org/10.1371/journal.pone.0350803 June 4, 2026 1 / 12 the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: No datasets were generated or analyzed during the current study. All relevant data from this study will be made available upon study completion. Funding: This work was supported by the Japan Agency for Medical Research and Development (AMED; grant number JP25ck0106033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. San Medical Co., Ltd. provided the investigational material (Soft Protector CPC) for the study. Competing interests: The authors received financial support from the Japan Agency for Medical Research and Development (AMED; grant number JP25ck0106033). This study was also supported by San Medical Co., Ltd., which provided the investigational material (Soft Protector CPC). This does not alter our adherence to PLOS ONE policies on sharing data and materials. with the potential to improve the patients’ quality of life and adherence to cancer therapy. This study was approved by the Clinical Research Review Board and registered with the Japan Registry of Clinical Trials, jRCTs062250005, on April 18, 2025. Introduction Oral mucositis is a common and debilitating side effect in cancer patients undergoing chemotherapy or radiotherapy. It involves inflammation and ulceration of the oral mucosa, causing severe pain and affecting the patient’s ability to eat, drink, and maintain oral hygiene. This condition can significantly reduce quality of life and may lead to treatment interruptions or dose reductions, potentially compromising cancer therapy outcomes [1–3]. Current management strategies for oral mucositis have limited effectiveness and effect duration. They often require frequent application and fail to address the mechanical irritation from teeth, which can exacerbate symptoms [4–6]. To overcome these limitations, novel approaches such as protective oral devices are being investigated to provide more comprehensive and longer-lasting relief for patients with chemotherapy-induced oral mucositis. To address these issues, we developed a novel mucosal protectant, Soft Protector CPC, which has been approved as a medical device (Sun Medical Co., Ltd., approval no. 30500BZX00107000). The newly developed Soft Protector CPC differs from conventional therapies in that it is applied to teeth that are likely to mechanically irritate the oral mucosa, rather than being applied directly to ulcerated mucosal surfaces. By covering such teeth, the device is intended to reduce local mechanical stimulation associated with oral mucositis-related pain. Furthermore, Soft Protector CPC exerts an inhibitory effect on biofilm accumulation at its surface through the sustained release of cetylpyridinium chloride (CPC), an antimicrobial agent. Therefore, protective materials are expected to suppress the progression of dental caries and gingivitis/periodontitis. A previous exploratory, randomized, controlled, two-arm, open-label trial was conduc (...truncated)