An Open Label Phase I/II Study of Humanized Human Milk Fat Globule-1 (THEREX) in Patients With Locally Advanced or Metastatic Breast Cancer Following Prior Anthracycline and Taxane Therapy

OBJECTIVES:

• Determine the safety and tolerability of monoclonal antibody HuHMFG1 in women with locally advanced or metastatic breast cancer previously treated with anthracycline and taxane-based therapy.
• Determine the maximum tolerated dose and appropriate schedule of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Determine the tumor response rate, progression-free survival, and median survival of patients treated with this drug.
• Analyze immunological markers for evaluation of disease status (e.g., in vitro analysis of antibody-dependent cellular cytotoxicity, natural killer cell activity, complement depletion, and tumor markers CA 15.3 and CEA) in patients treated with this drug.

OUTLINE: This is a dose-escalation, open-label, nonrandomized, multicenter study.

• Phase I: Patients receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 3 weeks for doses 1 and 2. All subsequent dose intervals are based on individual half-life value of the drug. Patients receive at least 6 doses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 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 3 or 2 of 6 patients experience dose-limiting toxicity.