bms-247550 plus capecitabine in treating patients with metastatic breast cancer

Conditions: Breast Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining bms-247550 with capecitabine in treating patients who have metastatic breast cancer that has not responded to previous chemotherapy with a taxane and an anthracycline.

objectives: * determine the maximum tolerated dose of bms-247550 and capecitabine, on 2 different schedules, in patients with metastatic breast cancer previously treated with a taxane and an anthracycline. * determine the safety profile of this regimen in these patients. * determine, preliminarily, any antitumor activity of this regimen in these patients. outline: this is a dose-escalation study. patients are assigned to 1 of 2 groups. * group i: patients receive bms-247550 iv over 3 hours on day 1 and oral capecitabine twice daily on days 1-14. * group ii: patients receive bms-247550 iv over 1 hour on days 1-3 and capecitabine as in group i. treatment in both groups repeats every 3 weeks for 2-18 courses in the absence of disease progression or unacceptable toxicity. cohorts of 6 patients receive escalating doses of bms-247550 and capecitabine until the maximum tolerated dose (mtd) is determined for each group. the mtd is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. additional patients are treated at the mtd. patients are followed for at least 30 days and then every 3 months thereafter. projected accrual: approximately 34-60 patients will be accrued for this study within 8-12 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed breast cancer * metastatic disease by radiography or histology * must have received prior chemotherapy with a taxane and an anthracycline in the adjuvant or metastatic setting * no more than 2 prior chemotherapy regimens in the metastatic setting * measurable or evaluable disease * bone lesions not measurable * primary breast lesions not measurable if assessed only by physical exam * no active brain metastasis * no cerebral edema by ct scan or mri * no progression since prior imaging studies * no requirement for steroids * no clinical symptoms of brain metastasis * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * not specified menopausal status * not specified performance status * ecog 0-1 life expectancy * at least 3 months hematopoietic * absolute neutrophil count at least 2,000/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 9.0 g/dl hepatic * bilirubin no greater than 1.5 times upper limit of normal (uln) * alt no greater than 2.5 times uln renal * creatinine less than 1.5 times uln cardiovascular * no uncontrolled or significant cardiovascular disease * no myocardial infarction within the past year * no uncontrolled angina within the past year * no history of congestive heart failure * no history of atrial or ventricular arrhythmias * no history of second- or third-degree heart block * no uncontrolled hypertension other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no hypersensitivity to cremophor el or fluorouracil * no prior intolerance to fluoropyrimidines * no other serious uncontrolled medical disorder or active infection that would preclude study * no dementia or altered mental status that would preclude study * no grade 2 or greater neuropathy (neuromotor or neurosensory) prior concurrent therapy: biologic therapy * see chemotherapy * prior immunotherapy allowed * no concurrent trastuzumab (herceptin) * no concurrent immunotherapy chemotherapy * see disease characteristics * at least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or doxorubicin hcl liposome) * at least 2 years since prior high-dose chemotherapy with bone marrow transplantation or peripheral blood stem cell support * no prior epothilone, capecitabine, or continuous-infusion fluorouracil * no other concurrent chemotherapy endocrine therapy * prior hormonal therapy allowed * no concurrent hormonal therapy * concurrent hormone replacement therapy allowed radiotherapy * at least 3 weeks since prior radiotherapy * no prior radiotherapy to more than 25% of the bone marrow * no concurrent therapeutic radiotherapy surgery * not specified other * at least 3 weeks since prior investigational cytotoxic agents * no concurrent warfarin for therapeutic anticoagulation * low-dose warfarin allowed for implanted ports or indwelling catheters * no other concurrent experimental anticancer medications * no other concurrent antitumor therapy * concurrent bisphosphonates for palliation of bone metastases allowed if initiated before study

Keywords: recurrent breast cancer stage iv breast cancer