ucn-01 and topotecan in treating patients with recurrent, persistent, or progressive advanced ovarian epithelial, primary peritoneal, or fallopian tube cancer

Conditions: Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer

Summary: rationale: drugs used in chemotherapy, such as topotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. ucn-01 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. combining ucn-01 with topotecan may kill more tumor cells. purpose: phase ii trial to study the effectiveness of combining ucn-01 with topotecan in treating patients who have recurrent, persistent, or progressive advanced ovarian epithelial, primary peritoneal, or fallopian tube cancer.

objectives: primary * determine the antitumor activity of ucn-01 and topotecan, in terms of complete and partial objective response rates, in patients with recurrent, persistent, or progressive advanced ovarian epithelial, primary peritoneal, or fallopian tube cancer. secondary * determine the antitumor activity of this regimen, in terms of stable disease rates and duration of response, in these patients. * determine the progression-free, median, and overall survival of patients treated with this regimen. * determine the safety and tolerability of this regimen in these patients. * determine the relationship between clinical and pharmacodynamic effects of this regimen in these patients. outline: this is a multicenter study. patients receive ucn-01 iv over 3 hours on day 1 and topotecan iv over 30 minutes on days 1-5. treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. projected accrual: a total of 19-33 patients will be accrued for this study within 5-11 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer * progressive, persistent, or recurrent disease * measurable disease outside prior radiotherapy field unless disease progression occurred after radiotherapy * tumor lesions accessible for biopsy * patients with a medical contraindication to tumor biopsy may be allowed at the discretion of the principal investigator * no more than 2 prior chemotherapy regimens * at least 1 regimen must have contained a platinum agent (i.e., carboplatin or cisplatin) * no known brain metastases patient characteristics: age * 18 and over performance status * ecog 0-2 or * karnofsky 60-100% life expectancy * more than 12 weeks hematopoietic * wbc at least 3,000/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic * bilirubin no greater than upper limit of normal (uln) * ast/alt no greater than 2.5 times uln renal * creatinine no greater than uln or * creatinine clearance at least 50 ml/min cardiovascular * no history of coronary artery disease * no symptomatic cardiac dysfunction * no cardiac pathology by electrocardiogram\* note: \*patients with symptomatic coronary artery disease must undergo an electrocardiogram pulmonary * no symptomatic pulmonary dysfunction other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for at least 8 weeks after study participation * no prior allergic reaction attributed to compounds of similar chemical or biological composition to ucn-01 or other study agents * no insulin-dependent diabetes mellitus * diabetes controlled by diet or oral hypoglycemic agents allowed at the discretion of the investigator * no other concurrent uncontrolled illness * no ongoing or active infection * no psychiatric illness or social situation that would preclude study compliance prior concurrent therapy: biologic therapy * more than 4 weeks since prior biologic therapy and recovered chemotherapy * see disease characterisitcs * more than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * no prior topotecan * no other prior topoisomerase i inhibitors endocrine therapy * more than 4 weeks since prior hormonal therapy and recovered radiotherapy * see disease characteristics * more than 4 weeks since prior radiotherapy and recovered * no prior radiotherapy to more than 40% of bone marrow * no prior mediastinal irradiation surgery * more than 4 weeks since prior surgery and recovered other * no other concurrent anticancer therapy * no other concurrent investigational agents * no concurrent combination antiretroviral therapy for hiv-positive patients

Keywords: stage iv ovarian epithelial cancer recurrent ovarian epithelial cancer primary peritoneal cavity cancer fallopian tube cancer stage iii ovarian epithelial cancer