A Safety and Efficacy Trial of TV5M01 for Radiation-Induced Mucositis in Patients Undergoing Treatment for Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Incidence of superficial bacterial and fungal infections
研究概览
简要总结
This study is a Phase 2, double-blind, randomized controlled trial evaluating the safety and efficacy of TV5M01 (a 5% green tea and 0.1% morphine gel) compared to triple mixture (0.19% lidocaine, 0.29% nystatin, and 5.50% hydroxides) for treating radiation-induced oral mucositis in patients with head and neck squamous cell carcinoma.
The trial will enroll 40 patients (20 per group) with stage III-IV head and neck cancer receiving radiotherapy who develop grade 1 or higher mucositis. Participants will apply the assigned mouthwash three times daily from mucositis diagnosis until resolution.
Primary outcomes include safety (incidence of infections and adverse events) and efficacy (duration of grade 3-4 mucositis, days with severe pain). Secondary outcomes include quality of life and analgesic use. Randomization will use minimization methodology to balance important prognostic factors.
The study design incorporates two interim analyses after 10 and 19 participants, with clear safety monitoring and stopping rules. If successful, this trial could provide an evidence-based treatment option for radiotherapy-induced mucositis, potentially improving treatment completion rates and quality of life for head and neck cancer patients.
详细描述
Detailed Description
This Phase 2a randomized, double-blind controlled trial evaluates the efficacy and safety of TV5M01 (a 5% green tea extract and 0.1% morphine gel) for treatment of radiation-induced oral mucositis in head and neck cancer patients. Mucositis affects virtually all patients receiving radiotherapy for head and neck cancer, causing significant pain, impaired nutrition, and often necessitating treatment interruptions. Despite its prevalence, no effective evidence-based treatments exist.
The scientific rationale for TV5M01 combines two complementary mechanisms: the antioxidant and anti-inflammatory properties of green tea extract (epigallocatechin gallate) and the targeted analgesic effects of low-dose morphine. Preclinical studies demonstrate that EGCG inhibits radiation-induced cellular damage through multiple pathways, including reduction of reactive oxygen species, attenuation of pro-inflammatory cytokine expression, and mitigation of DNA damage. Topical morphine provides localized pain relief with minimal systemic absorption through peripheral opioid receptors that become upregulated in inflamed tissues.
This single-center trial will enroll 40 participants with stage III-IV squamous cell carcinoma of the head and neck who develop grade 1 or higher mucositis during radiotherapy. Participants will be randomized in a 1:1 ratio to receive either TV5M01 or triple mixture ("magic mouthwash" containing lidocaine, nystatin, and hydroxides) as 10mL oral rinses administered three times daily until mucositis resolution. The randomization employs a minimization algorithm to balance treatment groups across key prognostic factors including age, sex, tumor location, and histopathological grade.
To maintain blinding, both preparations will appear similar and will be dispensed in identical amber PET bottles. Stability studies confirm a 7-day shelf life when stored at 5°C. Comprehensive assessments include daily mucositis grading, pain scores, weekly oropharyngeal examinations with photographic documentation, and quality of life measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and < 60 years
- •Diagnosis of HNSCC of the oral cavity, larynx, oro- and hypopharynx, diagnostic stage III-IV according to the AJCC 8th edition, scheduled to start radiotherapy
- •Ability to swallow solids and liquids before starting radiotherapy treatment
- •Adequate contraception for both sexes:
- •For women: negative pregnancy test for women of childbearing age; must be surgically sterile, postmenopausal (defined as absence of menstrual cycle for at least 12 consecutive months), or comply with an acceptable contraceptive regimen during and 3 months after the treatment period
- •For men: must be surgically sterile or comply with a contraceptive regimen during and for 3 months after the treatment period
- •Performance status (ECOG) of 0-1, measured within 72 hours prior to treatment initiation
- •Expected life expectancy ≥ 6 months
- •Adequate renal function [creatinine ≤ 1.5 times the upper limit of normal (ULN) or Glomerular Filtration Rate ≥ 50 ml/min]
- •Adequate liver function [total bilirubin ≤ 1.5 x ULN; AST or ALT ≤ 3 x ULN or ≤ 5 x ULN if due to tumor liver involvement]
- •Provision of signed and dated informed consent before initiating any study-related procedure
- •Meeting the diagnostic criteria for grade 1 or higher mucositis according to WHO classification
- •Meeting the criteria for starting radiotherapy
- •Willing and able to participate in the trial and comply with all trial requirements
排除标准
- •Patients not eligible for radiotherapy
- •Stomatological disease such as ulcers, edema, exudation in the oropharyngeal mucosa before radiotherapy
- •Women who are pregnant or breastfeeding
- •Patients allergic or sensitive to any of the compounds in the gel or study medications
- •Presence of lesions that completely occlude the upper digestive tract
- •Patients with a history of disorders, specifically those with psychotic psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder, and substance/alcohol abuse
- •Patients participating or who have participated in another clinical trial in the last 30 days
- •Another uncontrollable, severe, hemodynamically unstable concurrent medical condition requiring urgent attention or threatening the patient's life
- •Receiving chemotherapy regimens with delayed toxicity within the last 4 weeks (six weeks for nitrosourea or mitomycin C) or continuous or weekly chemotherapy regimen with limited potential for delayed toxicity within the last two weeks
- •Any evidence of oral infection or disease in the oral cavity other than HNSCC
- •Any important medical disease or incidental abnormal laboratory finding that could increase the participant's risk in the study (based on the investigator's judgment)
- •Concomitant therapy with drugs that inhibit or enhance opioid action
- •Hypersensitivity to opioids, respiratory depression, obstructive airway disease, acute liver disease, seizure disorder, increased intracranial pressure, paralytic ileus, patients with known sensitivity to morphine, pheochromocytoma, acute asthma exacerbations, history of cardiac arrhythmia, heart failure.
研究组 & 干预措施
TV5M01 Oral Gel for Radiation-Induced Mucositis
This arm will receive TV5M01 oral gel (5% green tea extract with 0.1% morphine) as an oral rinse. Participants will use 10 mL of the preparation three times daily at 8-hour intervals (±2 hours) from the diagnosis of grade 1 or higher mucositis throughout radiation therapy or until mucositis resolves. The medication should be administered at consistent times daily without fasting requirements. Doses vomited while in clinic may be replaced; however, participants should not take replacement doses for self-administered doses vomited at home. Missed doses should be skipped rather than doubled at the next scheduled time.
干预措施: Green Tea Extract with Morphine (Combination Product)
Triple Mixture Oral Rinse for Radiation-Induced Mucositis
This arm will receive a Triple Mixture oral rinse (combination of 0.19% w/w Lidocaine, 0.29% w/w Nystatin, and 5.50% w/v Hydroxides). Participants will use 10 mL of the preparation three times daily at 8-hour intervals (±2 hours) from the diagnosis of grade 1 or higher mucositis until mucositis resolves. The medication should be administered at consistent times daily without fasting requirements. Doses vomited while in clinic may be replaced; however, participants should not take replacement doses for self-administered doses vomited at home. Missed doses should be skipped rather than doubled at the next scheduled time.
干预措施: Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis (Combination Product)
结局指标
主要结局
Incidence of superficial bacterial and fungal infections
时间窗: From the first day of TV5M01 application (initiated at diagnosis of mucositis during radiotherapy) through completion of radiotherapy (approximately 7 weeks) plus 30 days after the last radiotherapy cycle, for a total duration of approximately 10-11 week
To assess the safety profile of TV5M01 by measuring the occurrence of oral and pharyngeal superficial bacterial and fungal infections throughout the treatment period. These infections will be diagnosed through clinical examination and confirmed by culture testing when appropriate. The comparative incidence rates between the treatment arms will be analyzed using Fisher's exact test to determine any statistically significant differences in infection risk. This endpoint is critical for evaluating the local mucosal safety of the intervention, particularly given the immunocompromised status of patients undergoing radiotherapy.
次要结局
未报告次要终点
研究者
Angela Zambrano
Principal Investigator
Fundacion Clinica Valle del Lili