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.

Condition	Treatment or Intervention	Phase
intraocular melanoma Melanoma	Drug: FR901228  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the response rate in patients with unresectable stage III or stage IV malignant melanoma treated with FR901228.

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 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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
• 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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35233,  United States; Recruiting
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611-3013,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-3236,  United States; Recruiting

Study chairs or principal investigators

David H. Lawson, MD,  Study Chair,  Winship Cancer Institute of Emory University   
Sanjiv S. Agarwala, MD,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000415355; ECOG-E1603; NCT00104884
Record last reviewed:  February 2005
Last Updated:  March 15, 2005
Record first received:  March 3, 2005
ClinicalTrials.gov Identifier:  NCT00104884
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08