FR901228 in Treating Patients With Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. Determine the efficacy and safety of FR901228 (depsipeptide) in patients with metastatic breast cancer.

SECONDARY OBJECTIVES:

I. Determine the clinical activity of this drug, in terms of progression-free survival, 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.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 2.4-12.3 months.

Inclusion criteria

• Histologically or cytologically confirmed breast cancer

• Metastatic disease
• Measurable disease

• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• The following are not considered measurable disease:

• Bone disease only
• Pleural effusion
• Peritoneal effusion
• Must have received prior anthracycline (doxorubicin or epirubicin) and/or taxane (paclitaxel or docetaxel) as adjuvant therapy or for advanced disease

• Therapy with high-dose regimens or bone marrow transplantation is considered 1 prior regimen
• No known brain metastases
• Hormone receptor status:

• Not specified
• Male or female
• Performance status - ECOG 0-1
• Performance status - Karnofsky 70-100%
• More than 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal
• AST or ALT ≤ 2.5 times upper limit of normal
• Creatinine normal
• Creatinine clearance ≥ 60 mL/min
• QTc < 500 msec
• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No uncontrolled dysrhythmia
• No poorly controlled angina
• No other significant cardiac disease
• No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to FR901228
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No concurrent biologic agents
• No more than 1 prior chemotherapy regimen for metastatic disease
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior FR901228 (depsipeptide)
• No other concurrent chemotherapy
• Prior hormonal therapy for metastatic disease or as adjuvant therapy allowed
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy
• More than 2 weeks since prior minor surgery and recovered
• More than 4 weeks since prior major surgery and recovered
• Concurrent bisphosphonates allowed provided therapy was initiated ≥ 3 months ago
• No concurrent agents that cause QTc prolongation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs known to have histone deacetylase activity (e.g., valproic acid)
• No other concurrent investigational agents
• No other concurrent anticancer therapy