FR901228 in Treating Patients With Metastatic Breast Cancer

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