ParonychiaPhase 3NCT06643416
Efficacy and Safety of Add-on Timolol for EGFR-TKI and ALK-TKI Induced Paronychia
A Phase 3 study testing Timolol 0.5% eye drops and betamethasone valerate 0.1% cream and Betamethasone valerate 0.1% cream in people with Paronychia and EGFR-TKI, run by Queen Mary Hospital, Hong Kong at 1 site in Hong Kong.
Trial summary
To assess the clinical efficacy of add-on topical timolol 0.5% eye drops to betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paronychia, EGFR-TKI, ALK-TKI
- What is being tested?
- Timolol 0.5% eye drops and betamethasone valerate 0.1% cream and Betamethasone valerate 0.1% cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteHong Kong
- Study dates
- 9 Oct 2024to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or above, either males or females.
- Received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer.
- Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use
- Written informed consent obtained from patient
- Subjects are diagnosed with advanced non-small cell lung cancer
Who cannot join
- 1. Age below18
- 2. Patients who are allergic to, or contraindicated to topical timolol use
- 3. Pregnant women or nursing mother
- 4. Non-consenting patients
- 5. Subjects are not diagnosed with advanced non-small cell lung cancer
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Queen Mary Hospital
Hong Kong
85222555336
About this study
Official title: Efficacy and Safety of Add-on Topical Timolol in the Management of Epidermal Growth Factor and Anaplastic Lymphoma Kinase Receptor Tyrosine Kinase Inhibitor-induced Paronychia: a Prospective Randomized Open-labelled Trial
To assess the clinical efficacy of add-on topical timolol 0.5% eye drops to betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia.
Read the detailed description
Lung cancer is the second leading cause of cancer and the leading cause of cancer-related death in Hong Kong. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer patients. Adenocarcinoma and squamous cell carcinoma accounts for 40% and 25-30% of NSCLC patients, respectively. More than 75% of patients are diagnosed with stage III and IV lung cancer. The age-standardized one-year overall survival rate of stage III and IV NSCLC are 35-46% and 15.9-15.6%, respectively. Therefore, the management of locally advanced and metastatic lung cancer is important to improve the overall survival of NSCLC patients.
The management of locally advanced and metastatic NSCLC is actionable driver mutation dependent. Patients are recommended to have tissue biopsy to detect the actionable driver mutation. Epidermal growth factor receptor (EGFR) mutation accounts for 55.4% of actionable driver mutation in Hong Kong. Patients with EGFR mutation positive are recommended to receive EGFR tyrosine kinase inhibitor (EGFR-TKI) by the European Society of Medical Oncology and the National Comprehensive Cancer Network. Anaplastic lymphoma kinase (ALK) is another common is actionable driver mutation with tyrosine kinase inhibitor (TKI) including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.
Paronychia is one of the common adverse events in patients who receive EGFR-TKI(s) and other TKI. 17.6-57% of patients experienced paronychia in randomized controlled trials. There were 0.6-11% of patients who experienced grade 3 paronychia according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0) in randomized controlled trials.
Timolol and betaxolol are beta-blockers, which are hypothesized to be effective in managing paronychia. Beta-blockers were effective in hemangiomas and has been the first line treatment for severe infantile hemangiomas. Previous case reports and case series suggested the potential use of topical beta-blocker. However, the evidence of topical beta-blocker treatment was limited by small sample size and low level of evidence. Therefore, this study aims to compare the safety and efficacy of topical timolol with routine clinical care with paronychia (fingernails, toenails, or both) as an adverse effect of EGFR-TKI and ALK-TKI.
This study would assess the clinical efficacy of add-on topical timolol 0.5% eye drops to betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia. Eligible patients, who develop paronychia (affecting fingernails, toenails or both), will be included in this study. They will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% eye drops and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily. Patients in timolol combination treatment group will receive topical timolol 0.5% eye drops twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlusion for 1 month. Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% lotion twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks , up to 12 weeks to see the effect.
- Conditions
- Paronychia, EGFR-TKI, ALK-TKI
- Being tested
- Timolol 0.5% eye drops and betamethasone valerate 0.1% cream, Betamethasone valerate 0.1% cream
- Keywords
- EGFR TKI, paronychia, timolol, ALK-TKI
- Medical subject headings
- Paronychia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol 0.5% eye drops and betamethasone valerate 0.1% creamDrug
Topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect.
Betamethasone valerate 0.1% creamDrug
The management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect.
| Study group | Role | What they receive |
|---|---|---|
| Timolol combination treatment | Active comparator | Patients will received topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. Receives: Drug: Timolol 0.5% eye drops and betamethasone valerate 0.1% cream; Drug: Betamethasone valerate 0.1% cream |
| Routine Arm | Other | Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. Receives: Drug: Betamethasone valerate 0.1% cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% lotion
The proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% lotion
Measured: From baseline to month 3
Secondary outcomes (5)
The proportion of patients achieved complete or partial response
Proportion of patients achieved complete or partial response (improvement in at least 1 of these 3 items).
Measured: From baseline to month 3
Lack of response as well as proportion of patients with reduced severity of paronychia
Proportion of patients lack of response (improvement in less than 1 item)
Measured: From baseline to month 3
Change in chronic paronychia severity index scale with treatment
Involvement of 1 nail fold = 1; involvement of 2 nail folds [proximal or/and lateral] = 2; bilateral lateral nail fold involvement and proximal nail fold involvement = 3), edema (absent = 0; mild = 1; moderate = 2; severe = 3), erythema (absent = 0; mild = 1; moderate = 2; severe = 3), nail plate changes (absent = 0; mild = 1; moderate = 2; severe = 3), and cuticle involvement (normal = 0; damaged = 1; absent = 2), producing a combined total score (between 0 [min.] and 14 [max.]
Measured: From baseline to month 3
The improvement of paronychia by 4 point scale
1: 0 to <30%, 2: 30 to <50%, 3: 50 to 75%, 4: 75 to 100% improvement
Measured: From baseline to month 3
Change in severity of pain by Visual Analog Scale
VAS scores ≤3.4cm corresponded to mild pain-related interference with functioning, scores of 3.5-6.4 to moderate interference, and scores ≥6.5 to severe interference.
Measured: From baseline to month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2024
- Study start9 Oct 2024 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for ParonychiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 40 Adult patients aged 18 or above who received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer, who develop paronychia (affecting fingernails, toenails or both),as an adverse event from EGFR-TKI use will be included in this study. Patients will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% eye drops and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary Hospital, Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kwok Wang Chun, Queen Mary Hospital, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06643416
- Sponsor's protocol ID
- UW 24-573
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2024
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: privacy and confidentiality
Publications
Atis G, Goktay F, Altan Ferhatoglu Z, Kaynak E, Sevim Kecici A, Yasar S, Aytekin S. A Proposal for a New Severity Index for the Evaluation of Chronic Paronychia. Skin Appendage Disord. 2018 Nov;5(1):32-37. doi: 10.1159/000489024. Epub 2018 May 30.
PubMed 30643778Martinez-de-Espronceda I, Bernabeu-Wittel J, Azcona M, Monserrat MT. Recalcitrant trametinib-induced paronychia treated successfully with topical timolol in a pediatric patient. Dermatol Ther. 2020 Jan;33(1):e13164. doi: 10.1111/dth.13164. Epub 2019 Nov 15.
PubMed 31705590Sibaud V, Casassa E, D'Andrea M. Are topical beta-blockers really effective "in real life" for targeted therapy-induced paronychia. Support Care Cancer. 2019 Jul;27(7):2341-2343. doi: 10.1007/s00520-019-04690-8. Epub 2019 Mar 7.
PubMed 30847700Walters S, Maringe C, Coleman MP, Peake MD, Butler J, Young N, Bergstrom S, Hanna L, Jakobsen E, Kolbeck K, Sundstrom S, Engholm G, Gavin A, Gjerstorff ML, Hatcher J, Johannesen TB, Linklater KM, McGahan CE, Steward J, Tracey E, Turner D, Richards MA, Rachet B; ICBP Module 1 Working Group. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax. 2013 Jun;68(6):551-64. doi: 10.1136/thoraxjnl-2012-202297. Epub 2013 Feb 11.
PubMed 23399908Puttgen K, Lucky A, Adams D, Pope E, McCuaig C, Powell J, Feigenbaum D, Savva Y, Baselga E, Holland K, Drolet B, Siegel D, Morel KD, Garzon MC, Mathes E, Lauren C, Nopper A, Horii K, Newell B, Song W, Frieden I; Hemangioma Investigator Group. Topical Timolol Maleate Treatment of Infantile Hemangiomas. Pediatrics. 2016 Sep;138(3):e20160355. doi: 10.1542/peds.2016-0355. Epub 2016 Aug 15.
PubMed 27527799Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
PubMed 23816960Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15.
PubMed 24439929Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M, Yang JC, Mok T, Lee KH, Lu S, Shi Y, Lee DH, Laskin J, Kim DW, Laurie SA, Kolbeck K, Fan J, Dodd N, Marten A, Park K. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017 Feb 1;28(2):270-277. doi: 10.1093/annonc/mdw611.
PubMed 28426106Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
PubMed 22285168Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. Epub 2017 Sep 25.
PubMed 28958502Yatabe Y, Kerr KM, Utomo A, Rajadurai P, Tran VK, Du X, Chou TY, Enriquez ML, Lee GK, Iqbal J, Shuangshoti S, Chung JH, Hagiwara K, Liang Z, Normanno N, Park K, Toyooka S, Tsai CM, Waring P, Zhang L, McCormack R, Ratcliffe M, Itoh Y, Sugeno M, Mok T. EGFR mutation testing practices within the Asia Pacific region: results of a multicenter diagnostic survey. J Thorac Oncol. 2015 Mar;10(3):438-45. doi: 10.1097/JTO.0000000000000422.
PubMed 25376513Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S; ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237. doi: 10.1093/annonc/mdy275. No abstract available.
PubMed 30285222Cubiro X, Planas-Ciudad S, Garcia-Muret MP, Puig L. Topical Timolol for Paronychia and Pseudopyogenic Granuloma in Patients Treated With Epidermal Growth Factor Receptor Inhibitors and Capecitabine. JAMA Dermatol. 2018 Jan 1;154(1):99-100. doi: 10.1001/jamadermatol.2017.4120.
PubMed 29117285Yen CF, Hsu CK, Lu CW. Topical betaxolol for treating relapsing paronychia with pyogenic granuloma-like lesions induced by epidermal growth factor receptor inhibitors. J Am Acad Dermatol. 2018 Jun;78(6):e143-e144. doi: 10.1016/j.jaad.2018.01.015. Epub 2018 Jan 12. No abstract available.
PubMed 29339238Hagen R, Ghareeb E, Jalali O, Zinn Z. Infantile hemangiomas: what have we learned from propranolol? Curr Opin Pediatr. 2018 Aug;30(4):499-504. doi: 10.1097/MOP.0000000000000650.
PubMed 29846253
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Add-on Topical Timolol in the Management of Epidermal Growth Factor and Anaplastic Lymphoma Kinase Receptor Tyrosine Kinase Inhibitor-induced Paronychia: a Prospective Randomized Open-labelled Trial
- ClinicalTrials.gov ID
- NCT06643416
- Acronym / sponsor ID
- UW 24-573
- Conditions
- Paronychia, EGFR-TKI, ALK-TKI
- Keywords
- EGFR TKI, paronychia, timolol, ALK-TKI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Queen Mary Hospital, Hong KongUniversity, hospital or other
- Study start
- 9 Oct 2024 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 16 Oct 2024 (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.
To assess the clinical efficacy of add-on topical timolol 0.5% eye drops to betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia.
Detailed description
Lung cancer is the second leading cause of cancer and the leading cause of cancer-related death in Hong Kong. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer patients. Adenocarcinoma and squamous cell carcinoma accounts for 40% and 25-30% of NSCLC patients, respectively. More than 75% of patients are diagnosed with stage III and IV lung cancer. The age-standardized one-year overall survival rate of stage III and IV NSCLC are 35-46% and 15.9-15.6%, respectively. Therefore, the management of locally advanced and metastatic lung cancer is important to improve the overall survival of NSCLC patients.
The management of locally advanced and metastatic NSCLC is actionable driver mutation dependent. Patients are recommended to have tissue biopsy to detect the actionable driver mutation. Epidermal growth factor receptor (EGFR) mutation accounts for 55.4% of actionable driver mutation in Hong Kong. Patients with EGFR mutation positive are recommended to receive EGFR tyrosine kinase inhibitor (EGFR-TKI) by the European Society of Medical Oncology and the National Comprehensive Cancer Network. Anaplastic lymphoma kinase (ALK) is another common is actionable driver mutation with tyrosine kinase inhibitor (TKI) including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.
Paronychia is one of the common adverse events in patients who receive EGFR-TKI(s) and other TKI. 17.6-57% of patients experienced paronychia in randomized controlled trials. There were 0.6-11% of patients who experienced grade 3 paronychia according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0) in randomized controlled trials.
Timolol and betaxolol are beta-blockers, which are hypothesized to be effective in managing paronychia. Beta-blockers were effective in hemangiomas and has been the first line treatment for severe infantile hemangiomas. Previous case reports and case series suggested the potential use of topical beta-blocker. However, the evidence of topical beta-blocker treatment was limited by small sample size and low level of evidence. Therefore, this study aims to compare the safety and efficacy of topical timolol with routine clinical care with paronychia (fingernails, toenails, or both) as an adverse effect of EGFR-TKI and ALK-TKI.
This study would assess the clinical efficacy of add-on topical timolol 0.5% eye drops to betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia. Eligible patients, who develop paronychia (affecting fingernails, toenails or both), will be included in this study. They will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% eye drops and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily. Patients in timolol combination treatment group will receive topical timolol 0.5% eye drops twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlusion for 1 month. Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% lotion twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks , up to 12 weeks to see the effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 40 Adult patients aged 18 or above who received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer, who develop paronychia (affecting fingernails, toenails or both),as an adverse event from EGFR-TKI use will be included in this study. Patients will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% eye drops and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily.
| Arm | Type | Receives |
|---|---|---|
| Timolol combination treatment | Active comparator | Drug: Timolol 0.5% eye drops and betamethasone valerate 0.1% cream, Drug: Betamethasone valerate 0.1% creamPatients will received topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. |
| Routine Arm | Other | Drug: Betamethasone valerate 0.1% creamPatients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18 years or above, either males or females.
- Received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer.
- Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use
- Written informed consent obtained from patient
- Subjects are diagnosed with advanced non-small cell lung cancer
Key exclusion criteria (5 listed)
- 1. Age below18
- 2. Patients who are allergic to, or contraindicated to topical timolol use
- 3. Pregnant women or nursing mother
- 4. Non-consenting patients
- 5. Subjects are not diagnosed with advanced non-small cell lung cancer
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 |
|---|---|---|
| Timolol 0.5% eye drops and betamethasone valerate 0.1% creamTopical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. | Drug | Timolol combination treatment |
| Betamethasone valerate 0.1% creamThe management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks, up to 12 weeks to see the effect. | Drug | Routine Arm, Timolol combination treatment |
Primary outcome
The proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% lotion
Time frame: From baseline to month 3
The proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% lotion
5 secondary outcomes
The proportion of patients achieved complete or partial response
Time frame: From baseline to month 3
Lack of response as well as proportion of patients with reduced severity of paronychia
Time frame: From baseline to month 3
Change in chronic paronychia severity index scale with treatment
Time frame: From baseline to month 3
The improvement of paronychia by 4 point scale
Time frame: From baseline to month 3
Change in severity of pain by Visual Analog Scale
Time frame: From baseline to month 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2024.
- Background: PubMed 30643778Atis G, Goktay F, Altan Ferhatoglu Z, Kaynak E, Sevim Kecici A, Yasar S, Aytekin S. A Proposal for a New Severity Index for the Evaluation of Chronic Paronychia. Skin Appendage Disord. 2018 Nov;5(1):32-37. doi: 10.1159/000489024. Epub 2018 May 30.
- Background: PubMed 31705590Martinez-de-Espronceda I, Bernabeu-Wittel J, Azcona M, Monserrat MT. Recalcitrant trametinib-induced paronychia treated successfully with topical timolol in a pediatric patient. Dermatol Ther. 2020 Jan;33(1):e13164. doi: 10.1111/dth.13164. Epub 2019 Nov 15.
- Background: PubMed 30847700Sibaud V, Casassa E, D'Andrea M. Are topical beta-blockers really effective "in real life" for targeted therapy-induced paronychia. Support Care Cancer. 2019 Jul;27(7):2341-2343. doi: 10.1007/s00520-019-04690-8. Epub 2019 Mar 7.
- Background: PubMed 23399908Walters S, Maringe C, Coleman MP, Peake MD, Butler J, Young N, Bergstrom S, Hanna L, Jakobsen E, Kolbeck K, Sundstrom S, Engholm G, Gavin A, Gjerstorff ML, Hatcher J, Johannesen TB, Linklater KM, McGahan CE, Steward J, Tracey E, Turner D, Richards MA, Rachet B; ICBP Module 1 Working Group. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax. 2013 Jun;68(6):551-64. doi: 10.1136/thoraxjnl-2012-202297. Epub 2013 Feb 11.
- Background: PubMed 27527799Puttgen K, Lucky A, Adams D, Pope E, McCuaig C, Powell J, Feigenbaum D, Savva Y, Baselga E, Holland K, Drolet B, Siegel D, Morel KD, Garzon MC, Mathes E, Lauren C, Nopper A, Horii K, Newell B, Song W, Frieden I; Hemangioma Investigator Group. Topical Timolol Maleate Treatment of Infantile Hemangiomas. Pediatrics. 2016 Sep;138(3):e20160355. doi: 10.1542/peds.2016-0355. Epub 2016 Aug 15.
- Background: PubMed 23816960Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
- Background: PubMed 24439929Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15.
- Background: PubMed 28426106Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M, Yang JC, Mok T, Lee KH, Lu S, Shi Y, Lee DH, Laskin J, Kim DW, Laurie SA, Kolbeck K, Fan J, Dodd N, Marten A, Park K. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017 Feb 1;28(2):270-277. doi: 10.1093/annonc/mdw611.
- Background: PubMed 22285168Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
- Background: PubMed 28958502Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. Epub 2017 Sep 25.
- Background: PubMed 25376513Yatabe Y, Kerr KM, Utomo A, Rajadurai P, Tran VK, Du X, Chou TY, Enriquez ML, Lee GK, Iqbal J, Shuangshoti S, Chung JH, Hagiwara K, Liang Z, Normanno N, Park K, Toyooka S, Tsai CM, Waring P, Zhang L, McCormack R, Ratcliffe M, Itoh Y, Sugeno M, Mok T. EGFR mutation testing practices within the Asia Pacific region: results of a multicenter diagnostic survey. J Thorac Oncol. 2015 Mar;10(3):438-45. doi: 10.1097/JTO.0000000000000422.
- Background: PubMed 30285222Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S; ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237. doi: 10.1093/annonc/mdy275. No abstract available.
- Individual participant dataSharing planned: No. privacy and confidentiality
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Timolol 0.5% eye drops and betamethasone valerate 0.1% cream and Betamethasone valerate 0.1% cream in people with Paronychia and EGFR-TKI, run by Queen Mary Hospital, Hong Kong at 1 site in Hong Kong.
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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 18 Oct 2024. 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 Hong Kong. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wang Chun Kwok (+85222555336, kwokwch@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% lotion (time frame: From baseline to month 3). 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 NCT06643416, which also lists 17 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 18 Oct 2024.