Clinical trial NCT05165082: The Efficacy of Topical Timolol Combined With Cryotherapy in EGFR Inhibitors-induced Paronychia - a Double-blinded, Intrapatient Left-to-right Controlled Study
Official title: The Efficacy of Topical Timolol Combined With Cryotherapy in EGFR Inhibitor-induced Paronychia - a Double-blinded, Intrapatient Left-to-right Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Paronychia
Epidermal Growth Factor Receptor Inhibitor
Lead sponsor: Taipei Medical University WanFang Hospital
Sponsor class: OTHER
First posted: 2021-12-21
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: EGFR inhibitors (EGFRi) have been used to treat a wide variety of cancers nowadays. One of the major side effects of EGFRi is paronychia, which was not fatal but may caused huge negative impact on patient's daily activities. Current guidelines regarding EGFRi-induced paronychia suggested treatment with cryotherapy, topical corticosteroid or surgical intervention for Common Terminology Criteria for Adverse Events (CTCAE) grade 2 to grade 3 lesions. Recent studies showed that topical beta-blockers may be effective treatment for EGFRi- induced paronychia. However, the evidence was limited to case series and there was no randomized trials evaluating the efficacy.

Goal: To evaluate whether topical timolol combined with cryotherapy was more effective than cryotherapy alone in treating EGFR inhibitors-induced paronychia.

Method: In this single center, randomized, double-blinded, left-to-right comparison study, we plan to enroll 35 patients with EGFR inhibitors-induced paronychia. Patients eligible to enter this study should be over the age of 20 having at least one finger or toe involved with CTCAE grade 2\~3 paronychia on each of their hands or feet. The paronychia should have no indication for surgical treatment. After enrollment, one physician will randomize the hands or feet to either timolol-plus-cryotherapy group or cryotherapy-alone group using a computer-generated random allocation scheme. The side allocated to the timolol-plus-cryotherapy group will receive topical timolol solution twice daily (since the beginning of the allocation and continue for 8 weeks) and topical cryotherapy with liquid nitrogen every other week (at the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial). The other side allocated to cryotherapy-alone group will receive placebo (normal saline) twice daily (since the beginning of the allocation and continue for 8 weeks) and topical cryotherapy with liquid nitrogen every other week (at the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial). In the treatment phase, patients may receive additional local or systemic antibiotics according to the dermatologist's clinical judgement, but they can not receive topical silver nitrate, trichloroacetic acid or corticosteroid ointment. Patients are evaluated at baseline, at 2, 4, 6 and 8 weeks after the initiation of treatment. Efficacy endpoints include CTCAE grade, scoring system for paronychia related to oncologic treatments (SPOT) and physician global assessment, which are evaluated by a blinded investigator based on digital photos, and pain VAS score and patient global assessment, which are evaluated by questionnaire to the patients.


Eligibility criteria: Inclusion Criteria:

* EGFR inhibitors-induced paronychia
* Older than 20 years
* Having at least one finger or toe involved with CTCAE grade 2\~3 paronychia on each of their hands or feet

Exclusion Criteria:

* Indication for surgical treatment
* Medical history of asthma, severe COPD, sinus bradycardia, SA block, 2nd to 3rd degree AV conduction delay, heart failure, cariogenic shock or allergy to timolol

Primary outcomes:
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Evaluated at baseline
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Evaluated at week 2 after the initiation of intervention
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Evaluated at week 4 after the initiation of intervention
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Evaluated at week 6 after the initiation of intervention
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Evaluated at week 8 after the initiation of intervention
Secondary outcomes:
measure: Pain visual analogue scale
timeFrame: Evaluated at baseline, week 2, 4, 6 and 8 after the initiation of intervention
measure: Physician global assessment
timeFrame: Evaluated at week 2, 4, 6 and 8 after the initiation of intervention
measure: Patient global assessment
timeFrame: Evaluated at week 2, 4, 6 and 8 after the initiation of intervention
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taipei Municipal Wan-Fang Hospital
Study officials:
References:
citation: Chu CY, Chen KY, Wen-Cheng Chang J, Wei YF, Lee CH, Wang WM. Taiwanese Dermatological Association consensus for the prevention and management of epidermal growth factor receptor tyrosine kinase inhibitor-related skin toxicities. J Formos Med Assoc. 2017 Jun;116(6):413-423. doi: 10.1016/j.jfma.2017.03.001. Epub 2017 Mar 27.
citation: Yen CF, Hsu CK, Yang HS, Lee CN, Chi CC, Chung WH, Wang CL, Pang JS, Wang CW, Ko YS, Lu CW. Treatment of epidermal growth factor receptor inhibitor-induced severe paronychia with pyogenic granuloma-like lesions with topical betaxolol: an open-label observation study. Int J Dermatol. 2020 Mar;59(3):326-332. doi: 10.1111/ijd.14730. Epub 2019 Nov 25.