A Phase II Prospective, Open-Label, Randomized, Multicenter Study of Kangfu Spray for the Prevention of Radiation-Induced Oral Mucositis in Patients With Oral Malignancies Receiving Intensity-Modulated Radiotherapy

A Prospective, Open-Label, Randomized, Controlled, Multicenter Phase II Study of Kangfu Spray for the Prevention of Radiation-Induced Oral Mucositis in Patients With Oral Malignancies Undergoing Intensity-Modulated Radiotherapy

This is a prospective, open-label, randomized, controlled, multicenter phase II study evaluating the efficacy and safety of Kangfu Spray for the prevention of radiation-induced oral mucositis in patients with histologically confirmed oral malignancies receiving intensity-modulated radiotherapy (IMRT), with or without concurrent platinum-based chemotherapy.

Eligible participants will undergo definitive or postoperative adjuvant IMRT according to multidisciplinary team recommendations. Participants in the experimental group will receive Kangfu Spray prophylactically from the first day of radiotherapy until completion of radiotherapy, in addition to standard oral care. The primary endpoint is the incidence of severe radiation-induced oral mucositis, defined as World Health Organization (WHO) grade 3 or higher. Secondary endpoints include time to onset and duration of severe oral mucositis, incidence and duration of any oral mucositis, oral ulcer and pain scores, radiotherapy interruption, opioid analgesic use, nutritional indicators, quality of life, and safety. Exploratory analyses will evaluate lymphocytes, inflammatory factors, and microbiota in blood and saliva.

Radiation-induced oral mucositis is a common and clinically significant toxicity in patients with oral and head and neck malignancies receiving radiotherapy, particularly when concurrent chemotherapy is administered. Severe mucositis may result in pain, impaired oral intake, weight loss, treatment interruption, and reduced quality of life. Despite standard supportive care, the incidence of severe oral mucositis remains substantial.

Kangfu Spray is a medical radiation-protective product intended to reduce radiation-induced mucosal injury. According to the protocol and ethics materials, its proposed mechanism is related to free-radical scavenging, mainly through superoxide dismutase (SOD), thereby mitigating radiation-related mucosal damage. Preliminary data cited in the protocol suggest that Kangfu Spray may reduce the incidence and severity of radiation-induced oral mucositis and delay its onset in patients receiving radiotherapy for head and neck malignancies.

This study is an investigator-initiated, prospective, open-label, randomized, controlled, multicenter phase II trial. A total of 140 patients with histologically confirmed oral malignancies will be enrolled across 4 hospitals. Eligible patients must be scheduled to receive definitive or postoperative adjuvant IMRT, with or without concurrent platinum-based chemotherapy. Participants will be randomized to receive either Kangfu Spray plus standard oral care or standard oral care alone. In the experimental group, Kangfu Spray will be administered from the first day of radiotherapy until completion of radiotherapy, with 10 mL used at least 5 times daily and each administration lasting at least 1 minute. Suggested administration times are in the morning, before bedtime, approximately 30 minutes before radiotherapy, immediately after radiotherapy, and approximately 30 minutes after radiotherapy.

Oral mucositis will be assessed during radiotherapy and for 1 month after radiotherapy using WHO grading, the Oral Mucositis Assessment Scale (OMAS), and the Oral Mucositis Daily Questionnaire (OMDQ) mouth and throat soreness items. Additional evaluations include quality of life assessed by EORTC QLQ-C30, opioid analgesic use, nutritional indicators including body weight and PG-SGA, radiotherapy interruption, and safety assessed according to CTCAE version 5.0. Exploratory analyses will assess lymphocytes, inflammatory factors, and microbiota in blood and saliva. The primary endpoint is the incidence of severe oral mucositis, defined as WHO grade 3 or higher.

Inclusion Criteria:

• Histologically confirmed oral malignancy.
• Age 18 to 80 years.
• Karnofsky Performance Status (KPS) score >=70.
• Planned to receive definitive or postoperative adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemoradiotherapy, after multidisciplinary team evaluation.
• Adequate organ function, including white blood cell count >=2.0 x 10^9/L, absolute neutrophil count >=1.0 x 10^9/L, platelet count >=80 x 10^9/L, hemoglobin >=90 g/L, serum creatinine <=1.5 x upper limit of normal (ULN) or creatinine clearance >=50 mL/min, total bilirubin <=1.5 x ULN, and AST/ALT <=2.5 x ULN.
• Able to understand and comply with study procedures.
• Written informed consent provided.

Exclusion Criteria:

• Known allergy to Kangfu Spray or severe allergic predisposition.
• Uncontrolled immune-related oral mucosal disease or prior related immune mucosal disease.
• Pregnancy or breastfeeding.
• Prior radiotherapy to the head and neck region.
• Any severe concomitant disease or condition that, in the investigator's judgment, makes the participant unsuitable for participation.