NK cells of the bodys immune system are directed to destroy antibody targeted tumor cells. It has been reported that a natural humoral immune response to MUC1 protein in early breast cancer patients results in improved dis ease free survival. Interestingly, those patients with endogenous anti MUC1 antibodies had a significantly higher probability of freedom from distant metastases, selleck chem U0126 raising Inhibitors,Modulators,Libraries the possibility that the antibodies may be destroying Inhibitors,Modulators,Libraries circulating MUC1 positive tumor cells. The objectives of this multicenter phase I study were to deter mine the safety and pharmacokinetics as well as the maximal tolerated dose of AS1402 in patients with metastatic breast cancer. Materials and methods Patient eligibility Patients with advanced or metastatic breast cancer were eligi ble for this clinical trial.

Before initiation of the study at each investigational site, relevant study documentation was submit ted to and approved by the responsible local ethics commit tee, Colorado Multiple Institutional Review Board, Aurora, CO, Ochsner Clinical Foundation Institutional Review Board, New Orleans, LA, The University of Texas, MD Anderson Inhibitors,Modulators,Libraries Cancer Center Surveillance Committee, Houston, TX, Office for the Protection of Research Subjects, Los Angeles, CA, and Inhibitors,Modulators,Libraries West ern Institutional Review Board, Olympia, WA. The guidelines of the World Medical Association Declaration of Helsinki in its revised edition, the guidelines of ICH GCP, as well as the demands of national drug and data protection laws and other applicable regulatory requirements were strictly fol lowed.

Written informed consent was obtained from each patient before any study specific screening procedures Inhibitors,Modulators,Libraries were undertaken. Inclusion criteria Patients had to have histologically or cytologically confirmed breast cancer with overexpression of the MUC1 antigen on central immunohistochemistry assessment. Subjects had locally advanced or metastatic disease and had to have received no more than three prior chemotherapy regimens. They had to have previously received, with unsuccessful results, an anthracy cline and a taxane in any combination for the treatment of breast cancer, unless ineligible for these treatments owing to comorbidities or refusal of therapy. In addition, patients whose tumors were HER2 positive had to have relapsed after treat ment with trastuzumab. No restriction was posed for prior hormonal or biologic therapies or both.

Exclusion criteria Concurrent cytotoxic chemotherapy for metastatic breast can cer was not allowed. Patients with a left ventricular ejection fraction of less than 45%, as determined by multigated acqui sition scan or echocardiogram scans within 4 weeks of study entry, were excluded. Treatment plan It was planned to test doses of 1 mg kg, 3 mg kg, 9 mg kg, and 16 mg kg, selleck inhibitor according to the toxicity and pharmacokinetic profile observed at prior dose levels.