Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00121225
First received: July 19, 2005
Last updated: October 1, 2014
Last verified: May 2013

July 19, 2005
October 1, 2014
September 2005
March 2009   (final data collection date for primary outcome measure)
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00121225 on ClinicalTrials.gov Archive Site
  • Time to Progression Assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Effect of Vorinostat on HP1 and macroH2A Nuclear Foci [ Time Frame: Baseline and day 15 ] [ Designated as safety issue: No ]
    Compared with Fisher's exact test to determine utility as biomarkers of response.
  • Incidence of p53 Allelic Variations (72R or 72P) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Compared using Fisher's exact test with response.
  • Effect of Vorinostat on Serum Levels of VEGF and b-FGF [ Time Frame: Baseline, day 8 and day 15 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma
A Phase II Study of Vorinostat in Patients With Advanced Melanoma

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.

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
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
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.
Intervention: Drug: vorinostat
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
June 2013
March 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00121225
NCI-2009-00099, PHL-040, CDR0000436851, N01CM62203
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Naomi Balzer-Haas Princess Margaret Hospital Phase 2 Consortium
National Cancer Institute (NCI)
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP