- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00121225
Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma
A Phase II Study of Vorinostat in Patients With Advanced Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Ontario
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Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre at Hamilton Health Sciences
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Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital Phase 2 Consortium
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Toronto, Ontario, Canada, M5G 2M9
- University Health Network-Princess Margaret Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111-2497
- Fox Chase Cancer Center
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Rockledge, Pennsylvania, United States, 19046
- Fox Chase Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Time Frame: Up to 5 years
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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.
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Up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Progression Assessed by RECIST
Time Frame: Up to 5 years
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Up to 5 years
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Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes
Time Frame: Baseline and day 15
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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.
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Baseline and day 15
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Number of Patients With p53 Allelic Variations (72R or 72P)
Time Frame: Baseline
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Participants were assessed for p53 allelic variation at baseline
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Baseline
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Comparison of VEGF Serum Levels to Response to Vorinostat
Time Frame: Baseline, Day 1, Day 8 and Day 15
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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.
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Baseline, Day 1, Day 8 and Day 15
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Naomi Balzer-Haas, Princess Margaret Hospital Phase 2 Consortium
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Recurrence
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Vorinostat
Other Study ID Numbers
- NCI-2009-00099
- N01CM62203 (U.S. NIH Grant/Contract)
- PHL-040 (Other Grant/Funding Number: N01CM62203)
- CDR0000436851 (Other Grant/Funding Number: N01CM62203)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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