Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
This phase II trial studies how well vorinostat works in treating patients with metastatic melanoma of the eye. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Metastatic Intraocular Melanoma
Recurrent Intraocular Melanoma
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma|
- Objective response (complete and partial response) in patients with GNAQ/GNA11 mutant uveal melanoma [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]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.
- Adverse events classified by using the NCI CTCAE version 4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]At study closure, adverse events will be classified by type, grade, duration and probable relation to treatment.
- Time to progression [ Time Frame: From start of treatment until disease progression or date of last follow-up, assessed up to 1 year ] [ Designated as safety issue: No ]The product limit method will be used to estimate time to progression.
|Study Start Date:||April 2012|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO BID for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
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) mutational status.
II. To correlate clinical outcome with changes in histone acetylation status by immunohistochemistry.
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.
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Richard D. Carvajal 646-888-4161 email@example.com|
|Principal Investigator: Richard D. Carvajal|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Not yet recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Jeffrey A. Sosman 800-811-8480|
|Principal Investigator: Jeffrey A. Sosman|
|Principal Investigator:||Richard Carvajal||Memorial Sloan-Kettering Cancer Center|