combination chemotherapy in treating patients with stage ii, stage iii, or stage iv ovarian cancer

Conditions: Ovarian Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. combining more than one drug may kill more cancer cells. purpose: phase i/ii trial to study the effectiveness of topotecan combined with carboplatin and paclitaxel in treating patients who have stage ii, stage iii, or stage iv ovarian cancer.

objectives: * determine the maximum tolerated dose, dose-limiting toxicity, and quantitative and qualitative toxic effects of oral topotecan combined with intravenous carboplatin and paclitaxel in patients with stage iib, iic, iii, or iv ovarian epithelial cancer. (phase i closed to accrual 12/21/00) * evaluate the anti-tumor activity of this regimen in this patient population. outline: this is a multicenter, dose-escalation study of topotecan. patients receive oral topotecan on days 1-5 and paclitaxel iv over 3 hours followed by carboplatin iv over 30 minutes on day 5. courses repeat every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. * phase i: cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. (phase i closed to accrual 12/21/00) * phase ii: an additional 50 patients receive up to 6 courses of treatment as in phase i at the mtd. patients are followed every 3 months for 2 years and then every 6 months for 3 years. projected accrual: a total of 80 patients (30 in phase i and 50 in phase ii) will be accrued for this study. (phase i closed to accrual 12/21/00)

Eligibility criteria:
disease characteristics: * histologically confirmed stage iib, iic, iii, or iv ovarian epithelial cancer * measurable or evaluable lesion or microscopic residual disease after first surgery (phase ii patients) * no brain and/or leptomeningeal metastases by ct scan or mri unless asymptomatic without corticosteroid therapy patient characteristics: age: * 18 and over performance status: * ecog 0-2 life expectancy: * at least 3 months hematopoietic: * hemoglobin at least 9.0 g/dl * wbc at least 3,500/mm3 * absolute neutrophil count at least 1,500/mm3 * platelet count at least 100,000/mm3 hepatic: * bilirubin no greater than 1.5 times upper limit of normal (uln) unless liver metastases present * alkaline phosphatase no greater than 2 times uln\* * sgot no greater than 2 times uln\* note: \*no greater than 5 times uln if liver metastases present renal: * creatinine no greater than 1.5 times uln * creatinine clearance at least 60 ml/min cardiovascular: * no symptomatic cardiac disease, including clinical congestive heart failure or arrhythmias requiring treatment * no myocardial infarction within the past 3 months other: * no other malignancy except basal or squamous cell skin cancer or carcinoma in situ of the cervix * no uncontrolled infection * no complete bowel obstruction or other condition that would affect gi absorption or motility * no concurrent medical condition for which treatment with platinum, taxane, or camptothecin analogues are contraindicated * no other concurrent medical conditions that would preclude study * no mental disease * no history of allergy to platinum or taxanes, including drugs containing cremophor (e.g., cyclosporine or vitamin k) * not pregnant or nursing * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * no concurrent immunotherapy chemotherapy: * no prior camptothecin analogue * no prior chemotherapy for ovarian cancer * no other concurrent chemotherapy endocrine therapy: * see disease characteristics * no concurrent hormonal therapy other than estrogen replacement radiotherapy: * no concurrent radiotherapy surgery: * see disease characteristics other: * at least 30 days or 5 half-lives since any prior investigational therapy * no other concurrent investigational therapy * no concurrent metoclopramide or cisapride

Keywords: stage iib ovarian epithelial cancer stage iic ovarian epithelial cancer stage iiia ovarian epithelial cancer stage iiib ovarian epithelial cancer stage iiic ovarian epithelial cancer stage iv ovarian epithelial cancer