A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma
I. To determine the overall objective response rate (RR) to vorinostat in patients with
metastatic uveal melanoma harboring a GNAQ or GNA11 mutation.
I. To determine the overall survival (OS) of these patients. II. To determine the
progression-free survival (PFS) of these patients. III. To determine the tolerability of
vorinostat in patients with metastatic uveal melanoma.
I. To correlate overall objective RR with guanine nucleotide binding protein (G protein), q
polypeptide (GNAQ), guanine nucleotide binding protein (G protein), alpha 11 (Gq class)
(GNA11), and BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) (BAP1)
II. To correlate clinical outcome with changes in histone acetylation status by
III. To correlate clinical outcome with changes in known proliferation and apoptosis markers
including proliferation-related Ki-67 antigen (Ki67) by immunohistochemistry and BCL2-like
11 (apoptosis facilitator) (BIM), survivin, v-myc myelocytomatosis viral oncogene homolog
(avian) (c-myc), Mcl-1, cleaved poly (ADP-ribose) polymerase 1 (PARP), γ-H2A histone family,
member X (H2AX), and RAD51 homolog (S. cerevisiae) (RAD51) by western blot.
IV. To assess for changes in pathways, such as the mitogen-activated protein kinase (MAPK)
pathway, with treatment.
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response (complete and partial response) in patients with GNAQ/GNA11 mutant uveal melanoma
For this study a two-stage design will be used to evaluate objective response. At the final analysis, response will be classified by type and duration and 95% confidence intervals, adjusted for the interim looks, will be calculated.
Up to 1 year
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|