Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Stage IV Melanoma Clinical Trial

Official title:

A Phase II Study of Vorinostat in Patients With Advanced Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00121225
• Other study ID #: NCI-2009-00099
• Secondary ID: PHL-040CDR000043
• Status: Completed
• Phase: Phase 2
• Start date: September 2005
• Est. completion date: June 2013

Study information

• Verified date: January 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2013
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ciliary Body and Choroid Melanoma, Medium/Large Size
• Extraocular Extension Melanoma
• Iris Melanoma
• Melanoma
• Recurrent Intraocular Melanoma
• Recurrent Melanoma
• Stage IV Melanoma
• Uveal Melanoma

Intervention

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.

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Princess Margaret Hospital Phase 2 Consortium	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Rockledge	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Haas NB, Quirt I, Hotte S, McWhirter E, Polintan R, Litwin S, Adams PD, McBryan T, Wang L, Martin LP, vonMehren M, Alpaugh RK, Zweibel J, Oza A. Phase II trial of vorinostat in advanced melanoma. Invest New Drugs. 2014 Jun;32(3):526-34. doi: 10.1007/s1063 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)	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.	Up to 5 years
Secondary	Time to Progression Assessed by RECIST		Up to 5 years
Secondary	Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes	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.	Baseline and day 15
Secondary	Number of Patients With p53 Allelic Variations (72R or 72P)	Participants were assessed for p53 allelic variation at baseline	Baseline
Secondary	Comparison of VEGF Serum Levels to Response to Vorinostat	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.	Baseline, Day 1, Day 8 and Day 15