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

March 26, 2025 updated by: Angela Zambrano, Fundacion Clinica Valle del Lili

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Colombia
    • Valle del Cauca
      • Cali, Valle del Cauca, Colombia, 760031
        • Fundación Valle del Lili
        • Contact:
          • Liliana Vallecilla, MD
        • Contact:
          • Angela R Zambrano, MD
        • Contact:
          • Lina M Galvis, MD
        • Contact:
        • Contact:
        • Contact:
          • Mario M Barbosa, MD, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Combination product: Green Tea Extract with Morphine
TV5M01 is a novel oral rinse combining 5% green tea extract with 0.1% morphine in a gel formulation specifically designed for the treatment of radiation-induced oral mucositis. This unique combination leverages the antioxidant and anti-inflammatory properties of green tea polyphenols (particularly EGCG) with the analgesic effects of morphine delivered directly to the oral mucosa. Unlike other interventions, this formulation is administered as a 10 mL rinse three times daily with subsequent ingestion, targeting both local tissue healing and pain relief through a dual-action mechanism.
Active Comparator: 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.
Combination product: Active Comparator: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of superficial bacterial and fungal infections
Time Frame: 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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion Clinica Valle del Lili

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 28, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 7, 2025

First Submitted That Met QC Criteria

March 7, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 26, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025.18 (Other Identifier: Hospital Universitario Valle del Lili)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data publication policy: Our identifiable personal data (IPD) is not publicly available to protect participant privacy and confidentiality. We do not plan to share individual participant data with external researchers due to: 1) local regulatory restrictions, 2) the sensitive nature of the medical information collected, 3) limitations in our institutional data sharing infrastructure, and 4) commitments made to participants during the informed consent process regarding data confidentiality. Our ethics committee has approved this data management approach in accordance with Colombian regulations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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