Safety and Efficacy Trial of TV5M01 for Radiation-Induced Mucositis in Head and Neck Cancer Patients.

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. The trial incorporates robust safety monitoring with two planned interim analyses (after 13 and 26 participants). An independent Safety Monitoring Committee will review all adverse events and has authority to recommend early termination if safety concerns arise. Statistical analysis will employ non-parametric methods for efficacy comparisons, with sensitivity analyses using exact permutation techniques. If successful, this trial could establish TV5M01 as an evidence-based treatment for radiation-induced mucositis, potentially improving treatment adherence and quality of life for head and neck cancer patients. The dual mechanism targeting both inflammation and pain represents an innovative approach to this challenging clinical problem that has remained largely unsolved despite decades of research. A y los subtitulos de imporancia Detailed Description Background and Significance Head and neck squamous cell carcinoma represents a significant global health burden with increasing incidence in low and middle-income countries. Radiotherapy remains a cornerstone treatment modality, but oral mucositis develops in virtually 100% of patients receiving radiotherapy to the head and neck region. This complication frequently necessitates treatment modifications, potentially compromising oncologic outcomes and substantially impairing quality of life. Despite its prevalence and clinical impact, current treatment options for radiation-induced mucositis remain suboptimal. The commonly used "magic mouthwash" preparations have demonstrated limited efficacy in controlled trials and face challenges with coverage of affected areas and patient-reported adverse effects. Scientific Rationale The TV5M01 formulation combines two active components with complementary mechanisms targeting the pathophysiology of radiation-induced mucositis: The green tea extract (5%) contains epigallocatechin gallate (EGCG), which possesses potent antioxidant properties. In preclinical models, EGCG has demonstrated ability to inhibit radiation-induced apoptosis, reduce reactive oxygen species production, and attenuate pro-inflammatory pathways through NF-κB modulation. The morphine component (0.1%) provides targeted analgesia through peripheral opioid receptors that become upregulated in inflamed tissues. The pharmacokinetic profile supports limited systemic absorption when applied topically, providing site-specific pain relief without significant central effects. Study Design and Methodology This trial employs a randomized, double-blind, controlled, parallel-group design to evaluate the superiority of TV5M01 compared to triple mixture. The study will enroll 40 participants allocated in a 1:1 ratio to either intervention or control groups. Both preparations will be administered as 10mL oral rinses three times daily at 8-hour intervals, beginning upon diagnosis of grade 1 or higher mucositis and continuing until resolution or completion of radiotherapy. Randomization and Blinding The study utilizes a minimization randomization algorithm implemented through the REDCap platform to ensure balanced treatment groups across key prognostic factors including sex, age, tumor location, and histopathological grade. To maintain blinding, both preparations will appear similar in color and consistency, will be dispensed in identical amber PET bottles, and will be labeled with participant identification codes only. Monitoring and Safety Provisions An independent Safety Monitoring Committee will oversee trial conduct and participant safety. Two formal interim analyses are planned after enrollment of 13 and 26 participants, respectively. Pre-specified stopping rules include development of severe adverse events causally related to TV5M01, evidence of significant treatment inferiority at interim analyses, and regulatory safety alerts involving study components. Anticipated Impact If TV5M01 demonstrates superior efficacy compared to current standard approaches, it could significantly improve the management of radiation-induced mucositis, potentially enabling better adherence to planned radiotherapy regimens and enhancing quality of life during treatment. The dual-mechanism approach targeting both inflammatory processes and nociception represents an innovative strategy in addressing this challenging complication.