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

University of Washington15 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Male Breast Cancer

Interventions

ONTAKBIOLOGICAL

Given IV

flow cytometryOTHER

Correlative studies

immunohistochemistry staining methodOTHER

Correlative studies

enzyme-linked immunosorbent assayOTHER

Correlative studies

laboratory biomarker analysisOTHER

Correlative studies

protein expression analysisGENETIC

Correlative studies

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0

Subjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.

Time frame: 7 Days after last dose of ONTAK

Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry

The efficacy of ONTAK in depleting Tregs will be defined as a decrease in peripheral blood Tregs by 25% of each individual subject's baseline. All subjects will undergo blood draws at baseline and post ONTAK infusions at designated time points. Tregs from the peripheral blood will be quantitated using flow cytometry.