FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with unresectable stage III or stage IV malignant melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with unresectable stage III or stage IV malignant melanoma treated with FR901228 (depsipeptide). Secondary Determine the progression-free and overall survival of patients treated with this drug. Determine the toxicity profile of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive FR901228 (depsipeptide) intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study within 18 months.

Official Title
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Phase II Trial of Depsipeptide (NSC 630176) in Advanced Malignant Melanoma

Conditions
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Malignant Melanoma, Melanoma

Intervention / Treatment
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* Drug: Depsipeptide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III unresectable or American Joint Committee on Cancer (AJCC) stage IV cutaneous, mucosal, ocular, or unknown primary melanoma with measurable disease by physical examination or imaging studies. Palpable cutaneous or nodal metastases suitable for punch, trucut, or similar biopsy if the patient agrees. Normal electrocardiogram (EKG) Left ventricular ejection fraction (LVEF) > 40% by Multi Gated Acquisition Scan (MUGA) Corrected QT (QTc) < 500 msec Age greater than or equal to 18 Negative pregnancy test Fertile patients must use effective contraception Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 Normal organ and marrow function Patients on hydrochorthiazide should be switched to a potassium-sparing diuretic or another antihypertensive At least 4 weeks since prior radiotherapy Patients with cardiac hypertrophy may be enrolled but should be carefully monitored. Exclusion Criteria: Prior FR901228 (depsipeptide) Prior chemotherapy Other concurrent chemotherapy Active central nervous system (CNS) metastases by brain computed tomography (CT) scan or magnetic resonance imaging (MRI) History of coronary atherosclerotic heart disease History of myocardial infarction History of congestive heart failure Non-melanoma malignancy within the past 5 years except carcinoma in situ or squamous cell or basal cell skin cancer Pregnant or nursing women Conditions that in the opinion of the investigator would interfere with the ability of the patient to complete this protocol History of allergic reactions attributed to compounds of similar chemical or biologic composition to Depsipeptide Co-medication with an agent that causes QTc prolongation Human immunodeficiency virus (HIV) positive patients receiving combination anti-retroviral therapy Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements Concurrent radiotherapy Left ventricular hypertrophy (LVH) on their baseline EKG tracing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Depsipeptide<br>Depsipeptide is administered as a 4-hour IV infusion weekly in doses of 13 mg/m^2 for 3 weeks. Repeat cycle every 28 days until unacceptable toxicity or disease progression. | Drug: Depsipeptide<br>* Given IV<br>* Other names: FK228;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Response to Depsipeptide | Response is evaluated using Solid Tumor Response Criteria (RECIST) and defined as either complete repose (CR) or partial response (PR). Per RECIST criteria, CR = disappearance of all target and nontarget lesions; PR = at least 30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. | Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 3 years from study entry, up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, Depsipeptide