Vorinostat in Treating Patients With Metastatic Melanoma of the Eye

NCT01587352 | Active Not Recruiting Phase 2

• 11 other identifiers: NCI-2012-0086012-027CUMC-IRBAAAO5917AAAO5917MSKCC-12-0279111N01CM00100N01CM62206P30CA008748U01CA069856UM1CA186689
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Metastatic Uveal Melanoma; Stage IV Uveal Melanoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 years

Secondary Outcomes (3)

• Overall survival

  From start of treatment to death or last follow-up will be estimated, assessed up to 3 years

• Progression free survival

  From start of treatment to date of progression, death or last follow-up will be estimated, assessed up to 3 years

• Incidence of toxicities

  Up to 3 years

Other Outcomes (3)

• Gnaq mutation status

  Up to day 15

• GNA11 mutation status

  Up to day 15

• BAP1 mutation status

  Up to day 15

Study Arms (1)

Treatment (vorinostat)

EXPERIMENTAL

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; Drug: Vorinostat

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vorinostat)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (vorinostat)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have metastatic histologically or cytologically confirmed uveal melanoma. (If histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma). Pathologic confirmation of diagnosis will be performed at Columbia University, Memorial Sloan-Kettering Cancer Center (MSKCC) or Vanderbilt University Medical Center
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Age \>= 18 years. Because limited dosing or adverse event data are currently available on the use of vorinostat in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric single-agent trials, if applicable
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9.0 g/dL not requiring transfusions within the past 2 weeks
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN); =\< 3 x institutional ULN if the patient has Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN if no liver metastasis present; =\< 5 x institutional ULN if liver metastases are present
• Creatinine =\< 1.5 mg/dL
• Ability to understand and the willingness to sign a written informed consent document
• Vorinostat is toxic to the developing human fetus. For this reason and because Class D agents are known to be teratogenic, women of child-bearing potential and men must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of vorinostat administration

You may not qualify if:

• Patients may have had any number of prior therapies. At least 3 weeks must have elapsed since the last dose of systemic therapy. At least 6 weeks must have elapsed if the last regimen included BCNU or mitomycin C. At least 6 weeks must have elapsed if the last regimen included an anti-CTLA4 antibody. Patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
• Patients who are receiving any other investigational agents
• Patients with active or untreated brain metastases. Treated brain metastases must have been stable for at least 2 months
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
• Patients receiving HDAC inhibitors or compounds with HDAC inhibitor like activity, such as valproic acid, are ineligible. Patients who have received such agents may enroll on this study after a 14-day washout period
• Patients on warfarin will be excluded from the trial if they cannot be switched to an acceptable alternative medication (i.e. low molecular weight heparin \[LMWH\]). Prolongation of prothrombin time (PT) and International Normalized Ratio (INR) were observed in patients receiving vorinostat concomitantly with coumarin-derivative anticoagulants
• Pregnant women are excluded from this study because vorinostat is a Class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy will be eligible unless the CD4 count is \< 200 cells/mm\^3 within one month of study enrollment (as requested by Cancer Therapy Evaluation Program \[CTEP\]). These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
• A second malignancy requiring active therapy
• No concomitant anti-cancer chemotherapy or other systemic drugs. Palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Corrected QT interval (QTc) \> 475 milliseconds
• Patients who cannot swallow capsules

Sponsors & Collaborators

• Institut Curie Paris: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Moffitt Cancer Center P2C: collaborator
• National Cancer Institute (NCI): lead

Study Sites (3)

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Alexander N Shoushtari

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: April 30, 2012
• Study Start: May 29, 2012
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-01

Locations

US (3)