edotecarin in treating women with locally advanced or metastatic breast cancer that has not responded to chemotherapy

Conditions: Breast Cancer

Summary: rationale: drugs used in chemotherapy such as edotecarin use different ways to stop tumor cells from dividing so they stop growing or die. purpose: this phase ii trial is studying how well edotecarin works in treating women with locally advanced or metastatic breast cancer that has not responded to previous chemotherapy.

objectives: primary * determine the antitumor activity of edotecarin in women with anthracycline- and taxane-refractory or chemoresistant locally advanced or metastatic breast cancer. secondary * determine the time to tumor response and duration of response in patients treated with this drug. * determine the overall survival of patients treated with this drug. * determine the clinical benefit of this drug in these patients. * determine the safety and tolerability of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. outline: this is an open-label, multicenter study. patients receive edotecarin iv over 1 hour on day 1. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. patients are followed every 2 months until disease progression. projected accrual: a total of 31-65 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed primary adenocarcinoma of the breast * locally advanced or metastatic disease * not amenable to surgery or radiotherapy with curative intent * at least 1 unidimensionally measurable lesion * at least 20 mm by conventional techniques or 10 mm by ct scan * not previously irradiated * meets 1 of the following criteria: * previously treated with anthracycline and concurrent or sequential taxane therapy * refractory to the most recent taxane-based chemotherapy, defined as 1 of the following: * progressive disease during therapy or within 4 months of the last dose with or without documented response for advanced disease * progressive disease within 6 months of completing taxane-based chemotherapy as neoadjuvant therapy * resistant to prior chemotherapy, as defined by progressive disease within 6 months of completing prior chemotherapy for advanced disease * no known brain metastases or carcinomatous meningitis\* note: \*baseline ct scan or mri of the brain required if there is clinical suspicion of cns metastases * no spinal cord compression * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * female menopausal status * not specified performance status * ecog 0-1 life expectancy * not specified hematopoietic * absolute neutrophil count at least 1,500/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) * sgot no greater than 2.5 times uln (5 times uln if liver involvement secondary to tumor is present) * albumin at least 3.0 g/dl renal * creatinine no greater than 1.5 mg/dl cardiovascular * lvef at least 50% or uln by echocardiogram or muga * none of the following within the past 6 months: * myocardial infarction * severe or unstable angina * symptomatic congestive heart failure * cerebrovascular accident or transient ischemic attack * deep vein thrombosis or other significant thromboembolic event * no ongoing cardiac dysrhythmias grade 2 or greater * no atrial fibrillation of any grade pulmonary * no pulmonary embolism within the past 6 months gastrointestinal * no active inflammatory bowel disease * no partial or complete bowel obstruction * no chronic diarrhea other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no known hiv positivity * no active infection * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation or confound study results prior concurrent therapy: biologic therapy * no concurrent biological response modifiers * no concurrent immunotherapy * no concurrent sargramostim (gm-csf) * no other concurrent granulocyte colony-stimulating factors chemotherapy * see disease characteristics * prior adjuvant chemotherapy allowed * no prior topoisomerase i inhibitors * no more than 2 prior chemotherapy regimens for advanced disease * no prior high-dose chemotherapy that required hematopoietic stem cell rescue * no other concurrent chemotherapy endocrine therapy * prior adjuvant hormonal therapy or hormonal therapy for advanced/metastatic disease allowed provided that therapy is discontinued before study entry * no concurrent hormonal therapy radiotherapy * see disease characteristics * no prior radiotherapy to more than 25% of the bone marrow * no concurrent radiotherapy during and for 5 days after study treatment * palliative radiotherapy allowed provided no more than 20% of the bone marrow is involved surgery * no coronary/peripheral artery bypass graft within the past 6 months other * recovered from prior therapy (except alopecia or neurotoxicity) * at least 4 weeks since any other prior therapy * more than 4 weeks since prior investigational agents * no concurrent enrollment on another clinical trial * no other concurrent approved or investigational anticancer treatment

Keywords: recurrent breast cancer stage iiia breast cancer stage iiib breast cancer stage iiic breast cancer stage iv breast cancer