(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma

Study Overview
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Brief Summary
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Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma

Detailed Description
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Phase 2 multi-center open-label IDE196 study in patients with primary uveal melanoma requiring either enucleation or plaque brachytherapy. Patients will be treated in neoadjuvant setting up to 6 months (or maximum benefit) followed by primary local therapy. An additional 6 months of adjuvant treatment to follow with long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease.

Official Title
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(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma

Conditions
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Uveal Melanoma

Intervention / Treatment
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* Drug: Darovasertib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary localized uveal melanoma requiring either enucleation or plaque brachytherapy Able to dose orally ECOG Performance status of 0-1 No other significant underlying ocular disease Adequate organ function Not pregnant/nursing or planning to become pregnant. Willing to use birth control Exclusion Criteria: Previous treatment with a Protein Kinase C (PKC) inhibitor Concurrent malignant disease Active HIV infection or Hep B/C Malabsorption disorder Unable to discontinue prohibited medication Impaired cardiac function or clinically significant cardiac disease Any other condition which may interfere with study interpretation or results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: darovasertib<br>IDE196 (darovasertib) oral open label | Drug: Darovasertib<br>* Oral, potent, selective inhibitor of Protein Kinase C<br>* Other names: LXS196;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) and significant laboratory abnormalities | Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs. Lab results will be summarized by change from baseline values, frequency of newly occurring on-treatment Grade 3 or 4 events; worst on-treatment value compared to baseline. | from first dose to last dose of adjuvant therapy, approximately 12 months | 
| Cohort 1 (enucleation): Number of patients converted from requiring enucleation to radiation | Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months | 
| Cohort 2 (plaque brachytherapy): Estimated change in modeled radiation dose | Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate tumor response to neoadjuvant IDE196 | Measurement of tumor diameter and thickness before and after neoadjuvant therapy with IDE196, specifically as measured by ocular ultrasound, evaluating largest basal diameter and apical thickness of the uveal melanoma (measured in millimeters) | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months | 
| Assessment of visual acuity loss | Best corrected visual acuity loss over time | from time of primary local therapy to one year after surgery, approximately 12 months | 
| Rate of local disease recurrence | Evaluate uveal melanoma progression or recurrence | from date of primary local therapy to end of follow-up, approximately 36 months | 
| Rate of metastatic disease | Evaluate occurrence of metastatic uveal melanoma | from date of primary local therapy to end of follow-up, approximately 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveal Melanoma, Plaque brachytherapy, Enucleation, Neoadjuvant, Adjuvant, Protein Kinase C, Ophthalmology, Ocular Oncology, Darovasertib, IDE196, Ocular melanoma, Choroid melanoma, Plaque, Brachytherapy