Efficacy and Safety of Timolol for TKI Induced Paronychia

Phase 3

Recruiting

Brief Summary: This study would assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-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% gel 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% gel twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlsuion 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.

Detailed Description: The aim of this study ist o assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-TKI induced paronychia.

Recruitment & Eligibility

Inclusion Criteria

Aged 18 years or above, either males or females.
Received EGFR-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib and mobocertinib.
Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use.
Written informed consent obtained from patient.

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Timolol combination treatment	Topical Timolol	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
Routine arm	Betamethasone Valerate	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.

Primary Outcome Measures

Name	Time	Method
The difference in the proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding)	From baseline to month 3	The primary outcome of this study is 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% cream.

Secondary Outcome Measures

Name	Time	Method
The proportion of patients achieved complete or partial response	From baseline to month 3	Proportion of patients achieved complete or partial response (improvement in at least 1 of these 3 items)
Change in chronic paronychia severity index scale with treatment	From baseline to month 3	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 \[max.\]
Lack of response as well as proportion of patients with reduced severity of paronychia	From baseline to month 3	Proportion of patients lack of response (improvement in less than 1 item)
The improvement of paronychia by 4 point scale	From baseline to month 3	1: 0 to \<30% , 2: 30 to \<50% ,3: 50 to 75% ,4: 75 to 100 % improvement)
Change in severity of pain by Visual Analog Scale	From baseline to month 3	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.