fr901228 in treating patients with relapsed or refractory advanced ovarian epithelial cancer

Conditions: Ovarian Cancer

Summary: 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.

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.

Eligibility criteria:
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

Keywords: recurrent ovarian epithelial cancer stage iii ovarian epithelial cancer stage iv ovarian epithelial cancer