FR901228 in Treating Patients With Relapsed or Refractory Advanced Ovarian Epithelial Cancer

Study Overview
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Brief Summary
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RATIONALE: FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory advanced ovarian epithelial cancer.

Detailed Description
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OBJECTIVES: Primary Determine the response rate (complete and partial) in patients with relapsed or refractory advanced ovarian epithelial carcinoma treated with FR901228 (depsipeptide). Determine the toxicity of this drug in these patients. Secondary Correlate clinical response with platinum sensitivity in patients treated with this drug. Correlate clinical response with P-glycoprotein expression or p53 status in patients treated with this drug. OUTLINE: This is multicenter study. Patients are stratified according to response to prior platinum administration (platinum resistant vs platinum sensitive). 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 20-37 patients will be accrued for this study within 12 months.

Official Title
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A Phase II Study Of Depsipeptide In Patients With Relapsed Or Refractory Ovarian Carcinoma

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: depsipeptide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed ovarian epithelial carcinoma Advanced disease Relapsed after OR refractory to 1, and only 1, prior platinum- or taxane-based regimen Refractory disease defined as disease progression during platinum- or taxane-based therapy Relapsed disease defined as platinum or taxane resistant or sensitive Platinum or taxane resistance defined as relapse within 6 months after prior platinum or taxane therapy Platinum or taxane sensitivity defined as relapse > 6 months from the last platinum or taxane treatment Measurable or evaluable disease Measurable disease defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Evaluable disease determined by elevation in CA 125 (≥ 2 times upper limit of normal [ULN]), ascites, or pleural effusion No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status SWOG 0-2 OR Karnofsky 60-100% Life expectancy At least 24 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 WBC ≥ 3,000/mm^3 Hepatic AST and ALT ≤ 2.5 times ULN Bilirubin normal Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular QTc < 500 msec LVEF > 40% by MUGA No significant cardiac disease No symptomatic congestive heart failure No unstable or poorly controlled angina pectoris No uncontrolled dysrhythmias No New York Heart Association class III or IV congestive heart failure No myocardial infarction within the past year No prior serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) 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 ≥ 2.0 mg/dL No prior allergic reaction attributed to compounds of similar chemical or biological composition to FR901228 (depsipeptide) No concurrent uncontrolled illness No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic agents Chemotherapy See Disease Characteristics More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior FR901228 (depsipeptide) No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery Prior surgical resection allowed Other No concurrent drugs known to have HDI activity (e.g., sodium valproate) No concurrent agents that cause QTc prolongation No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent hydrochlorothiazide No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: depsipeptide<br>Depsipeptide administered on Days 1, 8, and15 of a 28-day cycle. | Drug: depsipeptide<br> <br> * Other names: Romidepsin, Istodax®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of depsipeptide in ovarian cancer |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer