• Response rate [ Designated as safety issue: No ]
  
• Progression-free and overall survival [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

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) 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 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Diagnosis of malignant melanoma meeting 1 of the following stage criteria:

  • Unresectable stage III disease
  • Stage IV disease

• The following melanoma types are allowed:

  • Cutaneous
  • Mucosal
  • Ocular
  • Unknown primary

• Measurable disease by physical examination or imaging studies

  • Lesions on bone scan and positron-emission tomography are not considered measurable
  • Measurable disease must be outside a previously irradiated port
• Palpable cutaneous or nodal metastases suitable for punch, trucut, or similar biopsy

• No active CNS metastases by brain CT scan or MRI (performed < 4 weeks before study entry)

  • Solitary CNS lesions treated with surgery or stereotactic radiosurgery/gamma knife are allowed provided disease has been stable AND there is no evidence of new CNS lesions within the past 3 months

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• AST and/or ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No history of coronary atherosclerotic heart disease
• No history of myocardial infarction
• No history of congestive heart failure
• EKG normal
• LVEF > 40% by MUGA
• QTc < 500 msec
• No history of serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• Cardiac hypertrophy allowed

  • No left ventricular hypertrophy by EKG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Potassium ≥ 4.0 mmol/L
• Magnesium ≥ 2 mg/dL
• No nonmelanoma malignancy within the past 5 years except carcinoma in situ or squamous cell or basal cell skin cancer
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior immunotherapy, including any of the following:

  • Interferon
  • Interleukin
  • Sargramostim (GM-CSF)
  • Vaccines
• No concurrent biologic agents except filgrastim (G-CSF)

Chemotherapy

• No prior FR901228 (depsipeptide)
• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• Prior whole brain radiotherapy allowed
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• No prior coronary artery bypass graft or stent

Other

• At least 5 half-lives since prior and no concurrent agents that may cause QTc prolongation
• No other concurrent investigational agents
• No other concurrent antineoplastic agents
• No other concurrent drugs known to have histone deacetylase inhibitor activity (e.g., sodium valproate)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent hydrochlorothiazide