Efficacy and Safety of Add-on Timolol for EGFR-TKI and ALK-TKI Induced Paronychia

October 16, 2024 updated by: Kwok Wang Chun, Queen Mary Hospital, Hong Kong

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wang Chun Kwok
  • Phone Number: +85222555336
  • Email: kwokwch@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
          • Phone Number: 85222555336

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. Aged 18 years or above, either males or females.
  2. 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.
  3. Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use
  4. Written informed consent obtained from patient
  5. Subjects are diagnosed with advanced non-small cell lung cancer

Exclusion criteria

  1. 1. Age below18
  2. 2. Patients who are allergic to, or contraindicated to topical timolol use
  3. 3. Pregnant women or nursing mother
  4. 4. Non-consenting patients
  5. 5. Subjects are not diagnosed with advanced non-small cell lung cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Timolol combination treatment
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.
Drug: Timolol 0.5% eye drops and betamethasone valerate 0.1% cream
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.
Drug: Betamethasone valerate 0.1% cream
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.
Other: Routine Arm
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.
Drug: Betamethasone valerate 0.1% cream
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From baseline to month 3

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen Mary Hospital, Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 9, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 14, 2024

First Submitted That Met QC Criteria

October 14, 2024

First Posted (Actual)

October 16, 2024

Study Record Updates

Last Update Posted (Actual)

October 18, 2024

Last Update Submitted That Met QC Criteria

October 16, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 24-573

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

privacy and confidentiality

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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