Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm I
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.
干预措施: ONTAK (Biological)
Arm I
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.
干预措施: flow cytometry (Other)
Arm I
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.
干预措施: immunohistochemistry staining method (Other)
Arm I
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.
干预措施: enzyme-linked immunosorbent assay (Other)
Arm I
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.
干预措施: laboratory biomarker analysis (Other)
Arm I
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.
干预措施: protein expression analysis (Genetic)
结局指标
主要结局
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
时间窗: 7 Days after last dose of ONTAK
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.
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
时间窗: 21 days after cycle 6
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.
次要结局
- Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis(21 days after cycle 6)
- Presence of Circulating sIL-2R in the Peripheral Blood(21 days after cycle 6)
- Presence of Endogenous Tumor-specific Immunity(21 days after cycle 6)
- Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression(21 days after cycle 6)
研究者
Mary (Nora) Disis
Principal Investigator
University of Washington