biological therapy in treating women with stage iv breast cancer

Conditions: Breast Cancer

Summary: rationale: biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. combining different types of biological therapies may kill more tumor cells. purpose: phase i/ii trial to study the effectiveness of combining different biological therapies in treating women who have stage iv breast cancer.

objectives: * determine the maximum tolerated dose of armed activated t cells given in combination with interleukin-2 and sargramostim (gm-csf) in women with stage iv breast cancer. * determine the toxicity profile of this regimen in these patients. * determine the clinical response and overall and progression-free survival of patients treated with this regimen. outline: this is a dose-escalation study of armed activated t cells. patients undergo peripheral blood mononuclear cell (pbmc) collection. the pbmcs are treated ex vivo with monoclonal antibody okt3 to form armed activated t cells (atc). the armed atc are expanded for 14 days in interleukin-2 (il-2). patients receive armed atc iv over 30 minutes twice weekly for 4 weeks. patients also receive il-2 subcutaneously (sc) once daily and sargramostim (gm-csf) sc twice weekly beginning 3 days before the first infusion of armed atc and continuing until 7 days after the last infusion of armed atc. cohorts of 3-6 patients receive escalating doses of armed atc until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, additional patients are treated at that dose. patients are followed at 1, 2, and 5 months and then every 6 months thereafter. projected accrual: a total of 15-30 patients will be accrued for the phase i portion of this study and a total of 18-33 patients will be accrued for the phase ii portion of this study within 4-6 years. please note: this study was intended to be a phase i/ii study, but never moved forward to phase ii. (4-22-09)

Eligibility criteria:
disease characteristics: phase i: * histologically confirmed infiltrating ductal carcinoma of the breast * metastatic disease * clinically asymptomatic with non-life-threatening metastases allowed * measurable or evaluable disease by radiograph, ct scan, mri, nuclear medicine bone scan, or physical examination * no measurable disease allowed if tumor or metastasis has been removed or successfully treated prior to study * no rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs and liver) * stable or unstable disease for 3 months on hormonal therapy * stable or unstable disease for at least 1 month after chemotherapy * no active brain metastases * brain metastases previously treated with definitive radiotherapy and/or surgical resection allowed * hormone receptor status: * estrogen and progesterone receptor status known phase ii: * all phase i criteria * her2/neu overexpression (2+ or 3+) by immunohistochemistry * prior trastuzumab (herceptin) allowed if disease still overexpresses her2/neu patient characteristics: age: * 18 and over sex: * female menopausal status: * not specified performance status: * karnofsky 70-100% or * ecog 0-2 life expectancy: * at least 3 months hematopoietic: * granulocyte count at least 1,500/mm\^3 * platelet count at least 50,000/mm\^3 * hemoglobin at least 8 g/dl hepatic: * bilirubin less than 1.5 times normal * sgot less than 1.5 times normal renal: * creatinine no greater than 1.8 mg/dl * creatinine clearance at least 60 ml/min * bun no greater than 1.5 times normal cardiovascular: * no myocardial infarction within the past year * no prior myocardial infarction with coronary symptoms requiring medication and/or depressed left ventricular function (lvef less than 50% by muga) * no angina or coronary symptoms requiring medication and/or with depressed left ventricular function (lvef less than 50% by muga) * no congestive heart failure requiring medical management * lvef at least 50% at rest by muga * no uncontrolled hypertension (i.e., systolic blood pressure \[bp\] ≥ 130 mm hg or diastolic bp ≥ 80 mm hg) pulmonary: * fev1, dlco, and fvc at least 50% predicted other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no other serious medical or psychiatric illness that would preclude study participation * no other prior or concurrent malignancy within the past 5 years except curatively treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission prior concurrent therapy: biologic therapy: * see disease characteristics * prior trastuzumab allowed for phase i chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy endocrine therapy: * see disease characteristics * concurrent hormonal therapy for breast cancer must continue during study * no other concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes) radiotherapy: * see disease characteristics surgery: * see disease characteristics

Keywords: stage iv breast cancer recurrent breast cancer ductal breast carcinoma