monoclonal antibody huhmfg1 in treating women with locally advanced or metastatic breast cancer

Conditions: Breast Cancer

Summary: rationale: monoclonal antibodies such as huhmfg1 can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. purpose: this phase i trial is studying the side effects and best dose of monoclonal antibody huhmfg1 in treating women with locally advanced or metastatic breast cancer.

objectives: * determine the safety and tolerability of monoclonal antibody huhmfg1 in women with locally advanced or metastatic breast cancer. * determine a safe recommended dose and schedule of this drug in these patients. * determine the pharmacokinetic profile, in the absence of any other chemotherapy or endocrine agent, of this drug in these patients. * determine the antitumor activity of this drug in these patients. * determine time to progression in patients treated with this drug. * assess immunological markers (e.g., granzyme b, gamma interferon, and c1q) for determining response to this drug in these patients. * assess markers of immunogenicity (e.g., human anti-human antibody) of this drug in these patients. * assess tumor markers (e.g., ca15.3 and cea) in patients treated with this drug. * correlate, preliminarily, soluble hmfg1 antigen levels with pharmacokinetic data for this drug in these patients. outline: this is an open-label, non-randomized, dose-escalation study. patients in cohorts 1 and 2 receive monoclonal antibody huhmfg1 iv over 1-3 hours once every 21 days for doses 1 and 2. all subsequent dose intervals are based on individual half-life value of the drug, to be within 3 days of the estimated half-life in multiples of 7 days. patients in cohorts 3 and 4 receive monoclonal antibody huhmfg1 at the dosing interval determined in the first 2 cohorts. treatment continues in the absence of disease progression or unacceptable toxicity. cohorts of 6 patients receive escalating doses of monoclonal antibody huhmfg1 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. all patients are followed at 4 weeks and then every 6 weeks for 6 months. patients with an antitumor response or stable disease are followed every 12 weeks until disease progression or initiation of another antitumor treatment. projected accrual: a total of 6-24 patients will be accrued for this study within 18 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed breast cancer * locally advanced or metastatic disease * no inflammatory breast cancer * measurable (recist) or evaluable disease (e.g., cytologically or radiologically detectable disease that does not fulfill recist criteria) * failed prior or not a candidate for or refused anthracycline- and taxane-containing chemotherapy * patients whose tumor overexpresses her-2 must have failed prior trastuzumab (herceptin®) * no known cns metastases * no metastases accessible to complete surgical resection * unstained slides cut from formalin-fixed and paraffin-embedded tumor blocks available * appropriate tumor block also acceptable * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * female menopausal status * not specified performance status * who 0-1 life expectancy * at least 4 months hematopoietic * hemoglobin ≥ 10 g/dl * absolute neutrophil count ≥ 1,500/mm\^3 * wbc ≥ 1,000/mm\^3 * platelet count ≥ 100,000/mm\^3 hepatic * bilirubin ≤ 1.5 mg/dl * alt or ast ≤ 2.5 times upper limit of normal (uln) (\< 5 times uln in patients with liver metastases) or * alkaline phosphatase ≤ 2.5 times uln (\< 5 times uln in patients with liver metastases) * any degree of elevated alkaline phosphatase allowed provided it is due to bone metastases renal * creatinine ≤ 1.5 times uln or * creatinine clearance \> 60 ml/min * uric acid \< 1.25 times uln (for patients with hyperuricemia only) * calcium (corrected for serum albumin) \< 11.5 mg/dl (for patients with hypercalcemia only) cardiovascular * lvef ≥ 45% by muga or echocardiogram within the past 4 weeks other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective barrier contraception * no other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or cervical intra-epithelial neoplasia * no other uncontrolled illness that would preclude study participation prior concurrent therapy: biologic therapy * see disease characteristics * prior biological therapy allowed * more than 2 weeks since prior blood transfusions or growth factors to aid hematological recovery * no other concurrent antitumor immunotherapy chemotherapy * see disease characteristics * more than 4 weeks since prior cytotoxic chemotherapy * no more than 3 prior chemotherapy regimens, including adjuvant/neoadjuvant therapy * no concurrent antitumor chemotherapy endocrine therapy * prior hormonal therapy allowed * no concurrent corticosteroids except as physiologic replacement and/or for acute short-term treatment of, or prophylaxis against, infusion reactions * no concurrent antitumor hormonal therapy radiotherapy * see disease characteristics * more than 4 weeks since prior radiotherapy (except for palliative radiotherapy) * no concurrent antitumor radiotherapy, except for palliation to non-study lesions * irradiated area should be as small as possible and involve ≤ 10% of the bone marrow in any given 4-week period surgery * more than 4 weeks since prior major surgery other * more than 30 days since prior investigational agents * no other concurrent investigational agents

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