Squamous Cell Carcinoma of the Head and NeckPhase 1/2TEMORNCT06875791
Safety and Efficacy Trial of TV5M01 for Radiation-Induced Mucositis in Head and Neck Cancer Patients.
A Phase 1/2 study testing Green Tea Extract with Morphine and Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis in people with Squamous Cell Carcinoma of the Head and Neck and Oral Mucositis, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck, Oral Mucositis
- What is being tested?
- Green Tea Extract with Morphine and Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteColombia
- Study dates
- 28 Dec 2025to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Colombia1 site
Fundación Valle del Lili
Cali, Valle del Cauca Department, 760031
Liliana Vallecilla, MD, +6023319090 ext. 4022, liliana.vallecilla@fvl.org.co
Angela Zambrano, MD, +6023319090 ext. 7906, angela.zambrano@fvl.org.co
About this study
Official title: 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.
Read more
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.
Read the 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.
- Being tested
- Green Tea Extract with Morphine, Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis
- Keywords
- Oral mucositis, Squamous cell carcinoma
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Stomatitis, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Green Tea Extract with MorphineCombination product
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 MucositisCombination product
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
| Study group | Role | What they receive |
|---|---|---|
| TV5M01 Oral Gel for Radiation-Induced Mucositis | Experimental | 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. Receives: Combination Product: Green Tea Extract with Morphine |
| Triple Mixture Oral Rinse for Radiation-Induced Mucositis | Active comparator | 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. Receives: Combination Product: Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of superficial bacterial and fungal infections
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2025
- Study start28 Dec 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundacion Clinica Valle del Lili
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Angela Zambrano, Fundacion Clinica Valle del Lili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06875791
- Sponsor's protocol ID
- 2025.18
- Other IDs
- 2025.18
- Acronym
- TEMOR
- Status last verified
- Mar 2025
- First submitted
- 7 Mar 2025
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
Rosati M, Bramante S, Conti F, Frattari A, Rizzi M, Roman RA. Operative Gynecological Laparoscopy Under Conscious Sedation. JSLS. 2020 Apr-Jun;24(2):e2020.00020. doi: 10.4293/JSLS.2020.00020.
PubMed 32612345Liu YP, He RX, Chen ZH, Kang LL, Song JQ, Liu Y, Shi CY, Chen JY, Dong H, Zhang Y, Li MQ, Jin Y, Qin J, Yang YL. Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis. Front Nutr. 2023 May 12;10:1124387. doi: 10.3389/fnut.2023.1124387. eCollection 2023.
PubMed 37252234Gramegna A, Amati F, Terranova L, Sotgiu G, Tarsia P, Miglietta D, Calderazzo MA, Aliberti S, Blasi F. Neutrophil elastase in bronchiectasis. Respir Res. 2017 Dec 19;18(1):211. doi: 10.1186/s12931-017-0691-x.
PubMed 29258516Mourad R, Kolisnyk S, Baiun Y, Falk A, Yuriy T, Valerii F, Kopeev A, Suldina O, Pospelov A, Kim J, Rusakov A, Lebl DR. Performance of hybrid artificial intelligence in determining candidacy for lumbar stenosis surgery. Eur Spine J. 2022 Aug;31(8):2149-2155. doi: 10.1007/s00586-022-07307-7. Epub 2022 Jul 8.
PubMed 35802195Oit-Wiscombe I, Virag L, Soomets U, Altraja A. Increased DNA damage in progression of COPD: a response by poly(ADP-ribose) polymerase-1. PLoS One. 2013 Jul 24;8(7):e70333. doi: 10.1371/journal.pone.0070333. Print 2013.
PubMed 23894640Skeie EJ, Borge JA, Leboeuf-Yde C, Bolton J, Wedderkopp N. Reliability of diagnostic ultrasound in measuring the multifidus muscle. Chiropr Man Therap. 2015 Apr 15;23:15. doi: 10.1186/s12998-015-0059-6. eCollection 2015.
PubMed 25878771Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, Menendez PR, Pogany CE, Roth BM. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002 Nov 15;95(10):2230-6. doi: 10.1002/cncr.10938.
PubMed 12412178Zhu W, Mei H, Jia L, Zhao H, Li X, Meng X, Zhao X, Xing L, Yu J. Epigallocatechin-3-gallate mouthwash protects mucosa from radiation-induced mucositis in head and neck cancer patients: a prospective, non-randomised, phase 1 trial. Invest New Drugs. 2020 Aug;38(4):1129-1136. doi: 10.1007/s10637-019-00871-8. Epub 2019 Nov 7.
PubMed 31701429
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Trial of TV5M01 for Radiation-Induced Mucositis in Patients Undergoing Treatment for Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT06875791
- Acronym / sponsor ID
- TEMOR / 2025.18
- Keywords
- Oral mucositis, Squamous cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fundacion Clinica Valle del LiliUniversity, hospital or other
- Study start
- 28 Dec 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 13 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TV5M01 Oral Gel for Radiation-Induced Mucositis | Experimental | Combination Product: Green Tea Extract with MorphineThis 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. |
| Triple Mixture Oral Rinse for Radiation-Induced Mucositis | Active comparator | Combination Product: Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced MucositisThis 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Green Tea Extract with MorphineTV5M01 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. | Combination product | TV5M01 Oral Gel for Radiation-Induced Mucositis |
| Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced MucositisThis 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 | Triple Mixture Oral Rinse for Radiation-Induced Mucositis |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Background: PubMed 32612345Rosati M, Bramante S, Conti F, Frattari A, Rizzi M, Roman RA. Operative Gynecological Laparoscopy Under Conscious Sedation. JSLS. 2020 Apr-Jun;24(2):e2020.00020. doi: 10.4293/JSLS.2020.00020.
- Background: PubMed 37252234Liu YP, He RX, Chen ZH, Kang LL, Song JQ, Liu Y, Shi CY, Chen JY, Dong H, Zhang Y, Li MQ, Jin Y, Qin J, Yang YL. Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis. Front Nutr. 2023 May 12;10:1124387. doi: 10.3389/fnut.2023.1124387. eCollection 2023.
- Background: PubMed 29258516Gramegna A, Amati F, Terranova L, Sotgiu G, Tarsia P, Miglietta D, Calderazzo MA, Aliberti S, Blasi F. Neutrophil elastase in bronchiectasis. Respir Res. 2017 Dec 19;18(1):211. doi: 10.1186/s12931-017-0691-x.
- Background: PubMed 35802195Mourad R, Kolisnyk S, Baiun Y, Falk A, Yuriy T, Valerii F, Kopeev A, Suldina O, Pospelov A, Kim J, Rusakov A, Lebl DR. Performance of hybrid artificial intelligence in determining candidacy for lumbar stenosis surgery. Eur Spine J. 2022 Aug;31(8):2149-2155. doi: 10.1007/s00586-022-07307-7. Epub 2022 Jul 8.
- Background: PubMed 23894640Oit-Wiscombe I, Virag L, Soomets U, Altraja A. Increased DNA damage in progression of COPD: a response by poly(ADP-ribose) polymerase-1. PLoS One. 2013 Jul 24;8(7):e70333. doi: 10.1371/journal.pone.0070333. Print 2013.
- Background: PubMed 25878771Skeie EJ, Borge JA, Leboeuf-Yde C, Bolton J, Wedderkopp N. Reliability of diagnostic ultrasound in measuring the multifidus muscle. Chiropr Man Therap. 2015 Apr 15;23:15. doi: 10.1186/s12998-015-0059-6. eCollection 2015.
- Background: PubMed 12412178Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, Menendez PR, Pogany CE, Roth BM. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002 Nov 15;95(10):2230-6. doi: 10.1002/cncr.10938.
- Background: PubMed 31701429Zhu W, Mei H, Jia L, Zhao H, Li X, Meng X, Zhao X, Xing L, Yu J. Epigallocatechin-3-gallate mouthwash protects mucosa from radiation-induced mucositis in head and neck cancer patients: a prospective, non-randomised, phase 1 trial. Invest New Drugs. 2020 Aug;38(4):1129-1136. doi: 10.1007/s10637-019-00871-8. Epub 2019 Nov 7.
- Individual participant dataSharing planned: No. 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.
Related trials for Squamous Cell Carcinoma of the Head and Neck
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Green Tea Extract with Morphine and Active Comparator: Triple Mixture Oral Rinse for Radiation-Induced Mucositis in people with Squamous Cell Carcinoma of the Head and Neck and Oral Mucositis, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06875791, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.