Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00121225
Recruitment Status : Completed
First Posted : July 21, 2005
Results First Posted : October 3, 2014
Last Update Posted : January 29, 2019
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Condition or disease Intervention/treatment Phase
Ciliary Body and Choroid Melanoma, Medium/Large Size Extraocular Extension Melanoma Iris Melanoma Uveal Melanoma Recurrent Intraocular Melanoma Recurrent Melanoma Stage IV Melanoma Drug: vorinostat Phase 2

Detailed Description:


I. Determine the objective response rate in patients with metastatic or unresectable melanoma treated with vorinostat.


I. Determine time to progression in patients treated with this drug. II. Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in patients treated with this drug.

III. Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to progression in patients treated with this drug.

IV. Determine gene expression profiles that may predict response to this drug and gene expression changes that occur after treatment with this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then every 3 months thereafter.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Vorinostat in Patients With Advanced Melanoma
Study Start Date : September 2005
Actual Primary Completion Date : March 2009
Actual Study Completion Date : June 2013

Arm Intervention/treatment
Experimental: Arm I
Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.
Drug: vorinostat
Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

Primary Outcome Measures :
  1. Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 5 years ]
    Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.

Secondary Outcome Measures :
  1. Time to Progression Assessed by RECIST [ Time Frame: Up to 5 years ]
  2. Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes [ Time Frame: Baseline and day 15 ]
    Macro H2A and HP1 expression levels were compared through analysis of log fold changes in antibody expression in a multivariate general linear model between progressive disease and stable disease outcomes.

  3. Number of Patients With p53 Allelic Variations (72R or 72P) [ Time Frame: Baseline ]
    Participants were assessed for p53 allelic variation at baseline

  4. Comparison of VEGF Serum Levels to Response to Vorinostat [ Time Frame: Baseline, Day 1, Day 8 and Day 15 ]
    Blood specimens were collected from participants on Day 1 Cycle 1 prior to treatment (baseline), Day 1 3-4 hours following Vorinostat ingestion, Day 8 and Day 15. VEGF serum concentrations were detected using the Luminex multiplexed assay, where the median fluorescence intensity results were analyzed by a weighted five-parameter logistic method. The values were averaged across all time points per participant.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically/cytologically confirmed melanoma that is metastatic/unresectable
  • Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan, within 4 weeks prior to registration
  • No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C
  • Age>=18 years
  • Life expectancy >=3 months.
  • ECOG<2 (Karnofsky ≥60%)
  • Leukocytes >3,000/mcL
  • Absolute neutrophil count >1,500/mcL
  • Platelets >100,000/mcL
  • Total bilirubin within institutional limits
  • AST/ALT≤2.5Xinstitutional ULN
  • Creatinine within institutional limits OR creatinine clearance >60mL/min/1.73 m2 if creatinine levels above institutional limits
  • Eligibility of patients taking medications with potential to affect activity/PK of Vorinostat will be determined by PI
  • Must not use concomitant steroids except topical/inhaled use
  • Vorinostat effects on developing human fetus are unknown. Women of childbearing potential (WOCBP) and sexually active males must agree to use accepted/effective contraception method prior to study entry and for duration of the study
  • Ability to understand/willingness to sign written informed consent
  • Must have paraffin block of tumor tissue available for future studies

Exclusion Criteria:

  • Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study
  • May not be receiving any other investigational agents
  • Known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat
  • Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women excluded because Vorinostat is a HDAC inhibitor agent with potential for teratogenic or abortifacient effects
  • HIV-positive patients receiving combination antiretroviral therapy are ineligible because of potential for PK interactions with Vorinostat

Information from the National Library of Medicine

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 identifier (NCT number): NCT00121225

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Fox Chase Cancer Center
Rockledge, Pennsylvania, United States, 19046
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Naomi Balzer-Haas Princess Margaret Hospital Phase 2 Consortium

Publications of Results:
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00121225     History of Changes
Other Study ID Numbers: NCI-2009-00099
PHL-040 ( Other Grant/Funding Number: N01CM62203 )
CDR0000436851 ( Other Grant/Funding Number: N01CM62203 )
N01CM62203 ( U.S. NIH Grant/Contract )
First Posted: July 21, 2005    Key Record Dates
Results First Posted: October 3, 2014
Last Update Posted: January 29, 2019
Last Verified: January 2019

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action