This phase II trial studies how well vorinostat works in treating patients with melanoma of the eye that has spread to other parts of the body (metastatic). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To determine the overall objective response rate (RR) to vorinostat in patients with metastatic uveal melanoma. SECONDARY OBJECTIVES: I. Overall survival (OS). II. Progression free survival (PFS). III. To determine the tolerability of vorinostat in patients with metastatic uveal melanoma. EXPLORATORY OBJECTIVES: I. To correlate clinical outcome with changes in histone acetylation status by immunohistochemistry. II. To correlate clinical outcome with changes in known proliferation and apoptotic markers including Ki67 by immunohistochemistry and BIM, survivin, c-myc, Mcl-1, cleaved PARP, gamma-H2AX and RAD51 by western blot. III. To assess for changes in pathways such as the MAPK pathway with treatment. IV. To describe the evolution of circulating cell-free, tumor-derived deoxyribonucleic acid (DNA) levels measured by pyrophosphorolysis activated polymerization (PAP) in plasma of patients under treatment for metastatic uveal melanoma. V. To correlate overall objective RR with GNAQ, GNA11, SF3B1 and BAP1 mutational status. OUTLINE: Patients receive vorinostat orally (PO) twice daily (BID) for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Correlative studies
Given PO
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Overall response rate in patients with uveal melanoma
Defined as the rate of complete and partial responses. The response rate along with 90% confidence interval will be estimated.
Time frame: Up to 3 years
Overall survival
Overall survival curves will be generated using Kaplan-Meier methodology.
Time frame: From start of treatment to death or last follow-up will be estimated, assessed up to 3 years
Progression free survival
Progression-free survival curves will be generated using Kaplan-Meier methodology.
Time frame: From start of treatment to date of progression, death or last follow-up will be estimated, assessed up to 3 years
Incidence of toxicities
Assessed by National Cancer Institute Common Toxicity Criteria 4.0. Toxicity will be reported by type, frequency and severity.
Time frame: Up to 3 years
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