perifosine in treating patients with recurrent, refractory, locally advanced, or 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. purpose: phase ii trial to study the effectiveness of perifosine in treating patients who have recurrent, refractory, locally advanced, or metastatic breast cancer.

objectives: * determine the objective tumor response rate in patients with recurrent or refractory, locally advanced or metastatic breast cancer treated with perifosine. * determine the toxicity of this drug in these patients. * determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this drug. * correlate potential endpoints, including phosphorylated erk, pkb, and sapk, phosphorylated pkc alpha, beta, and gamma isoforms, p21 \^waf1; and activated capase-3 in tumor biopsies, with clinical outcome in patients treated with this drug. outline: this is an open-label, multicenter study. patients receive a loading dose of oral perifosine on days 1 and 2 and once daily on days 3-21 during course 1. patients receive oral perifosine once daily on days 1-21 in each subsequent course. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. patients achieving a complete response (cr) may receive 2 additional courses beyond the cr. projected accrual: a total of 18-35 patients will be accrued for this study within 6-12 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed breast cancer * recurrent or refractory, locally advanced or metastatic disease * at least 1 unidimensionally measurable lesion * at least 20 mm by conventional techniques or 10 mm by spiral ct scan * previously irradiated lesions are not considered measurable unless they have demonstrated progression before study entry * no measurable disease limited to bone lesions * no known brain metastases * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * male or female menopausal status * not specified performance status * ecog 0-2 or * karnofsky 60-100% life expectancy * more than 3 months 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 * no history of hemolytic disorder hepatic * bilirubin no greater than 1.25 times upper limit of normal (uln) * ast/alt no greater than 2.5 times uln (5 times uln if liver metastases present) renal * creatinine normal or * creatinine clearance at least 60 ml/min cardiovascular * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia * no evidence of cardiac dysfunction gastrointestinal * no history of biliary flow obstruction * no abnormalities of the gastrointestinal tract that would preclude study drug absorption * no active peptic ulcer disease other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no ongoing or active infection * no poorly controlled diabetes mellitus * no other uncontrolled illness * no prior allergic reactions to compounds of similar chemical or biological composition to perifosine * no psychiatric illness or social situation that would preclude study compliance prior concurrent therapy: biologic therapy * not specified chemotherapy * no more than 2 prior lines of chemotherapy for advanced disease, excluding adjuvant chemotherapy * prior adjuvant chemotherapy allowed * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered endocrine therapy * at least 4 weeks since prior endocrine therapy * multiple lines of endocrine therapy for advanced disease allowed radiotherapy * at least 4 weeks since prior radiotherapy and recovered * prior radiotherapy for metastatic disease allowed surgery * no prior major gastric surgery * prior surgery, including for metastatic disease, allowed other * no other concurrent anticancer or investigational agents * no concurrent antiretroviral therapy in hiv-positive patients * concurrent bisphosphonates allowed

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