The Efficacy of Topical Timolol Combined With Cryotherapy in EGFR Inhibitors-induced Paronychia - a Double-blinded, Intrapatient Left-to-right Controlled Study

NCT ID: NCT05165082

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-21
• Study Completion Date: 2023-03-21

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.

Conditions

Paronychia; Epidermal Growth Factor Receptor Inhibitor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Timolol plus cryotherapy

Apply topical timolol solution twice daily (since the beginning of the allocation and continue for 8 weeks) and cryotherapy with liquid nitrogen once every other week (on the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial).

Group Type: EXPERIMENTAL

Timolol maleate 0.5% ophthalmic solution

Intervention Type: DRUG

Apply on affected finger or toes twice daily for 8 weeks

Cryotherapy with liquid nitrogen

Intervention Type: PROCEDURE

Conducted on affected finger or toes every other week for four sessions.

Placebo plus cryotherapy

Apply placebo (normal saline) twice daily (since the beginning of the allocation and continue for 8 weeks) and cryotherapy with liquid nitrogen once every other week (on the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial).

Group Type: PLACEBO_COMPARATOR

Cryotherapy with liquid nitrogen

Intervention Type: PROCEDURE

Conducted on affected finger or toes every other week for four sessions.

Interventions

Timolol maleate 0.5% ophthalmic solution

Apply on affected finger or toes twice daily for 8 weeks

Intervention Type: DRUG

Cryotherapy with liquid nitrogen

Conducted on affected finger or toes every other week for four sessions.

Intervention Type: PROCEDURE

Other Intervention Names

Timoptol

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taipei Medical University WanFang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Huang Yu Chen

Yu-Chen Huang, MD, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Taipei Municipal Wan-Fang Hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: BACKGROUND

PMID: 28351555 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31763692 (View on PubMed)

Other Identifiers

N202104033

Identifier Type: -

Identifier Source: org_study_id