Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
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|ClinicalTrials.gov Identifier: NCT01587352|
Recruitment Status : Suspended (Other - Non-compliance with sponsor data reporting requirements)
First Posted : April 30, 2012
Last Update Posted : September 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ocular Melanoma With Extraocular Extension Recurrent Uveal Melanoma Stage IV Uveal Melanoma AJCC v7||Other: Laboratory Biomarker Analysis Drug: Vorinostat||Phase 2|
I. To determine the overall objective response rate (RR) to vorinostat in patients with metastatic uveal melanoma harboring a guanine nucleotide binding protein (G protein), q polypeptide (GNAQ) or guanine nucleotide binding protein (G protein), alpha 11 (Gq class) (GNA11) mutation.
I. Overall survival (OS). II. Progression free survival (PFS). III. To determine the tolerability of vorinostat in patients with metastatic uveal melanoma.
IV. To correlate overall objective RR with GNAQ, GNA11 and breast cancer 1 (BRCA1) associated protein-1 (ubiquitin carboxy-terminal hydrolase) (BAP1) mutational status.
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 BCL2-like 11 (apoptosis facilitator) (BIM), baculoviral IAP repeat containing 5 (survivin), v-myc avian myelocytomatosis viral oncogene homolog (c-myc), myeloid cell leukemia 1 (Mcl-1), cleaved poly (ADP-ribose) polymerase 1 (PARP), gamma-H2A histone family, member X (gamma-H2AX) and RAD51 recombinase (RAD51) by western blot.
III. To assess for changes in pathways such as the mitogen-activated protein kinase (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.
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 (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma|
|Actual Study Start Date :||April 20, 2012|
|Estimated Primary Completion Date :||November 30, 2020|
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: Laboratory Biomarker Analysis
- Overall response rate in patients with GNAQ/GNA11 mutant uveal melanoma, defined as the rate of complete and partial responses [ Time Frame: Up to 3 years ]The response rate along with 90% confidence interval will be estimated.
- Overall survival [ Time Frame: From start of treatment to death or last follow-up will be estimated, assessed up to 3 years ]Overall survival curves will be generated using Kaplan-Meier methodology.
- Progression free survival [ Time Frame: From start of treatment to date of progression, death or last follow-up will be estimated, assessed up to 3 years ]Progression-free survival curves will be generated using Kaplan-Meier methodology.
- Incidence of toxicities, assessed by National Cancer Institute Common Toxicity Criteria 4.0 [ Time Frame: Up to 3 years ]Toxicity will be reported by type, frequency and severity.
- Gnaq mutation status [ Time Frame: Up to day 15 ]Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
- GNA11 mutation status [ Time Frame: Up to day 15 ]Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
- BAP1 mutation status [ Time Frame: Up to day 15 ]Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01587352
|United States, New York|
|NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Richard D Carvajal||Columbia University/Herbert Irving Cancer Center|