Brief Title
Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
Official Title
A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma
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.
Detailed Description
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall response rate in patients with uveal melanoma
Secondary Outcome
Overall survival
Condition
Metastatic Uveal Melanoma
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Treatment (vorinostat)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
40
Start Date
April 20, 2012
Completion Date
December 31, 2023
Primary Completion Date
December 31, 2023
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Alexander N Shoushtari, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01587352
Organization ID
NCI-2012-00860
Secondary IDs
NCI-2012-00860
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Collaborators
Institut Curie Paris
Study Sponsor
Alexander N Shoushtari, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
February 2023