ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment

Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer

RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of immune cells from attacking the breast cancer cells.

PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects to see how well it works in treating patients with advanced breast cancer that did not respond to previous treatment.

PRIMARY OBJECTIVES:

I. To evaluate the safety of ONTAK infusion in patients with advanced refractory breast cancer.

II. To evaluate the effect of ONTAK administration on peripheral blood T-regulatory cells.

SECONDARY OBJECTIVES:

I. To evaluate the incidence of IL-2R expression in tumor samples and investigate the correlation of tumor IL-2R expression and tumor response to ONTAK therapy.

II. To evaluate levels of circulating sIL-2R before and after ONTAK therapy. III. To evaluate the effect of ONTAK on endogenous tumor specific immunity. IV. To evaluate the potential anti-tumor effects of ONTAK in patients with advanced refractory breast cancer.

OUTLINE:

Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

• Patients with advanced stage refractory breast cancer
• Progressive or relapsed disease following standard therapy
• Patients must have measurable disease that can include, but is not limited to bone; specifically, patients must have measurable extraskeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan; measurable (bi-dimensional) chest wall disease will also be allowed
• Patients must be at least 14 days out from last cytotoxic chemotherapy; patients on bisphosphonates are eligible
• White blood cell count (WBC) > 3.0 THOU/ul
• ANC > 1.0 THOU/ul
• Platelets >= 100 THOU/ul
• Serum creatinine =< 2.0 mg/dL or creatinine clearance (calculated) >= 60 ml/min
• ALT/AST =< 2.0 x upper limit of normal
• Total bilirubin =< 1.5 x upper limit of normal
• Albumin >= 3.0 g/dL
• Subjects must have a Performance Status Score (ECOG Scale) =< 2
• Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment
• Men and women of reproductive ability must agree to contraceptive use during the study and for 1month after ONTAK treatment is discontinued

Exclusion Criteria:

• Prior treatment with ONTAK (DAB389 IL-2) or DAB486 IL-2
• Known history of hypersensitivity to diphtheria toxin or IL-2
• Active autoimmune disease
• Known history of pulmonary disease except controlled asthma
• History of or pre-existing, cardiovascular disease as defined by New York Heart Association (NYHA) Class III-IV categorization
• Pregnant or breast-feeding women