This proof-of-concept study will evaluate the ability of vorinostat to induce the transformation of Class 2 uveal melanoma cells into a cell phenotype that resembles normal melanocytes.
This is a proof of concept, single-center, open-label study of an FDA-approved drug, vorinostat, a Histone deacetylase (HDAC) inhibitor, for patients with Class 2, high-risk uveal melanoma with localized eye tumors. The primary aim is to test if vorinostat can transform aggressive class 2 uveal melanoma cells into cells that look more like normal melanocytes as observed in the laboratory. Uveal melanoma patients that meet the inclusion criteria outlined in this protocol will be consented and asked to provide a fine needle aspiration (FNA) biopsy of their uveal melanoma primary tumor. This biopsy will be submitted for gene expression analysis to determine the phenotype of the tumor. A total of 10 patients who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of vorinostat daily for 15 days. On Day 15, patients will be asked to provide a second FNA biopsy prior to receiving the standard of care local definitive therapy either plaque radiotherapy or enucleation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Study participants who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of Vorinostat daily for 15 days.
Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
The investigators will analyze gene expression results from fine needle aspirate biopsies performed at baseline prior to vorinostat therapy and post-treatment (on Day 15, after the planned 15 days of vorinostat therapy).
Time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Proportion of patients whose tumors transformed from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
Through gene expression analysis, the investigators will determine the proportion of patients whose tumors transformed from a Class 2 phenotype into a cell phenotype that resembles normal melanocytes.
Time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Toxicity During Protocol Therapy
Rate of adverse events (AEs) and serious adverse events (SAEs) experienced by study participants during Vorinostat therapy and up to one month after Vorinostat treatment completion.
Time frame: Up to 1 Month Post-Treatment Completion
Tumor size before and after Vorinostat therapy
Tumor size will be determined before and after Vorinostat therapy by B-Scan ultrasonography.
Time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Recurrence-free survival (RFS)
Recurrence-Free Survival (RFS) in Study Participants. RFS is defined as the duration of time from start of treatment to time of disease recurrence or death, whichever occurs first.
Time frame: Up to 5 Years Post-Treatment Completion
Overall survival (OS)
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Overall Survival (OS) in Study Participants. OS is defined as the length of time from date of start of Vorinostat treatment to death.
Time frame: Up to 5 Years Post-Treatment Completion
Disease Specific Survival (DSS)
Disease Specific Survival (DSS) in Study Participants. DSS is defined as the time from start of Vorinostat treatment to death due to disease.
Time frame: Up to 5 Years Post-Treatment Completion