FR901228 in Treating Patients With Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying how well FR901228 works in treating patients with metastatic breast cancer. 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. FR901228 may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Study Of Single Agent Depsipeptide (FK228) In Breast Cancer

Conditions
-----------------
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
-----------------
* Drug: romidepsin
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (romidepsin)<br>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. | Drug: romidepsin<br>* Given IV<br>* Other names: Istodax;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy (complete and partial response) according to RECIST |  | Up to 14 months | 
| Progression-free survival |  | From the first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by the standard WHO grading system |  | Up to 14 months after completion of study treatment |