Malignant Melanoma, MEK Inhibitor-Associated Retinopathy
Conditions
Keywords
BRAF inhibitor, MEK inhibitor
Brief summary
Patients treated with BRAF/MEK inhibitor combinations for malignant melanoma may develop retinal changes known as MEK inhibitor-associated retinopathy (MEKAR). These changes can affect the structure and function of the retina and may cause visual symptoms. This prospective interventional study evaluates structural and functional retinal alterations in patients receiving BRAF/MEK inhibitor therapy. The study aims to determine how often MEKAR occurs, describe its clinical characteristics and course, compare its incidence between different BRAF/MEK inhibitor combinations, and assess possible long-term retinal changes after treatment discontinuation. Participants undergo structured ophthalmologic examinations, including visual acuity testing, retinal imaging, and functional retinal testing before treatment, two weeks after treatment initiation, during therapy if visual symptoms occur, and, when indicated, after treatment completion.
Detailed description
BRAF/MEK inhibitor combinations are commonly used in the treatment of malignant melanoma, including adjuvant and metastatic settings. During therapy, some patients develop retinal structural and functional alterations referred to as MEK inhibitor-associated retinopathy (MEKAR). This study is designed as a prospective, longitudinal, interventional clinical study conducted at the Institute of Oncology Ljubljana. All eligible adult patients with histologically confirmed malignant melanoma who initiate treatment with a BRAF/MEK inhibitor combination (dabrafenib/trametinib or vemurafenib/cobimetinib) are invited to participate. Participants undergo standardized ophthalmologic evaluations before initiation of therapy, two weeks after therapy initiation, and during treatment if visual symptoms occur. When MEKAR is diagnosed, follow-up examinations are performed at least six months after completion of therapy. The ophthalmologic assessment includes best-corrected visual acuity measurement, contrast sensitivity testing, slit-lamp examination after pharmacologic dilation, retinal imaging using optical coherence tomography (OCT), infrared and autofluorescence imaging, microperimetry, and electrooculography. In patients receiving adjuvant therapy who develop MEKAR involving the fovea, multifocal electroretinography is additionally performed at diagnosis and repeated after treatment completion. The study evaluates the incidence of MEKAR, changes in visual function, structural retinal alterations, differences between BRAF/MEK inhibitor combinations, and potential long-term retinal outcomes after therapy discontinuation.
Interventions
OTHEROphthalmologic Retinal Monitoring During BRAF/MEK Inhibitor Therapy
Participants treated with BRAF/MEK inhibitor combinations undergo ophthalmologic evaluation and retinal functional testing, including best-corrected visual acuity assessment, contrast sensitivity testing, slit-lamp examination, retinal imaging (OCT, infrared imaging, autofluorescence imaging), microperimetry, and electrophysiological testing (electrooculography and multifocal electroretinography when indicated) to detect MEK inhibitor-associated retinopathy (MEKAR) and assess retinal structural and functional alterations during and after therapy.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
All participants receiving BRAF/MEK inhibitor therapy undergo structured ophthalmologic examinations and retinal functional testing to detect and characterize MEK inhibitor-associated retinopathy (MEKAR) and evaluate retinal structural and functional alterations.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged 18 years or older * Histologically confirmed malignant melanoma * Treatment with a BRAF/MEK inhibitor combination (dabrafenib/trametinib or vemurafenib/cobimetinib) * Willingness to participate and provide written informed consent
Exclusion criteria
* Intraocular inflammation. * Uncontrolled glaucoma. * Retinal diseases (e.g., central serous chorioretinopathy). * Macular disorders. * High myopia (\> -6 diopters). * Other ocular or systemic diseases that could influence study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of MEK Inhibitor-Associated Retinopathy (MEKAR) | Baseline (Day 0) through end of treatment (up to 14 months) | Incidence of MEK inhibitor-associated retinopathy (MEKAR), defined as the proportion of participants who develop MEKAR during BRAF/MEK inhibitor therapy based on predefined clinical criteria and optical coherence tomography (OCT) findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retinal Structural Changes Assessed by Optical Coherence Tomography (OCT) | Baseline (Day 0); Week 2; and up to 14 months | Retinal structural alterations assessed by optical coherence tomography (OCT), including presence of neurosensory retinal detachment and other MEKAR-related changes. |
| Change in Best-Corrected Visual Acuity (BCVA) | Baseline (Day 0); Week 2; and up to 14 months | Change in best-corrected visual acuity (BCVA) measured during ophthalmologic examinations to assess visual function during BRAF/MEK inhibitor therapy. |
Countries
Slovenia
Outcome results
None listed