Phase II Trial of Anti-HER-2 Monoclonal Antibody Trastuzumab (Herceptin) in Combination With Low Dose Interleukin-2 (Proleukin) in Metastatic Breast Cancer Patients Who Have Previously Failed Trastuzumab
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
研究概览
简要总结
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Interleukin-2 may stimulate a person's white blood cells to kill breast cancer cells. Phase II trial to study the effectiveness of trastuzumab plus interleukin-2 in treating patients who have metastatic breast cancer that has not responded to previous trastuzumab therapy.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the response rate and toxicity to low-dose IL-2 with intermediate-"pulse" dose interleukin 2 (IL-2) and trastuzumab in patients with uni-dimensional measurable metastatic breast cancer and human epidermal growth factor receptor 2 (HER2) positive (3+ overexpression by immunohistochemistry [IHC] method or positive by fluorescent in situ hybridization [FISH]) who either have had evidence of progressive disease while receiving a trastuzumab-containing regimen, or have had progressive disease within 12 months of receiving a trastuzumab-containing regimen.
SECONDARY OBJECTIVES:
I. To perform correlative immunologic assays to determine the degree of natural killer (NK) cell expansion in response to low-dose IL-2, and the effectiveness of patients' peripheral blood mononuclear cells (PBMC) in a standard antibody-dependent cell-mediated cytotoxicity (ADCC) assay directed against a HER2 target cell.
II. To determine the pharmacokinetics of trastuzumab using an every 2-week schedule.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed breast cancer
- •Primary and/or metastatic disease
- •HER2 overexpression 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
- •Tumors with HER2 2+ overexpression by IHC allowed if confirmed by FISH
- •Progressive disease during or within 12 months of receiving prior regimen containing trastuzumab (Herceptin)
- •Unidimensionally measurable disease
- •At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- •The following are not considered measurable:
- •Bone metastases
- •Pleural or peritoneal effusion
- •Leptomeningeal disease
- •Lymphangitic disease
- •Inflammatory breast cancer
- •Cystic lesions
- •CNS lesions
- •CNS metastases allowed if all of the following conditions are met:
- •Asymptomatic
- •At least 3 months since prior surgery and/or cranial irradiation
- •At least 3 weeks since prior steroids
- •Hormone receptor status:
- •Not specified
- •Male or female
- •Performance status - ECOG 0-2
- •Granulocyte count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •SGOT and SGPT no greater than 2 times ULN (5 times ULN for liver metastases)
- •Alkaline phosphatase no greater than 2 times ULN (5 times ULN for liver metastases)
- •Creatinine no greater than 1.5 times ULN
- •LVEF at least lower limit of normal by MUGA or echocardiogram
- •No congestive heart failure or active ischemic heart disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No psychiatric illness, medical condition, or uncontrolled infection that would preclude study
- •No underlying immunodeficiency (e.g., HIV or autoimmune disease)
- •No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- •See Disease Characteristics
- •Prior cumulative doxorubicin dose no greater than 360 mg/m^2
- •At least 3 weeks since prior chemotherapy
- •No more than 2 prior chemotherapy regimens for metastatic disease
- •No concurrent chemotherapy
- •See Disease Characteristics
- •At least 3 weeks since prior endocrine therapy
- •No concurrent corticosteroids or dexamethasone
- •Concurrent hormones allowed for conditions unrelated to disease (e.g., insulin for diabetes)
- •See Disease Characteristics
- •At least 3 weeks since prior radiotherapy
- •No prior radiotherapy to study lesion, unless evidence of disease progression
- •No concurrent palliative radiotherapy
- 另有 3 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (trastuzumab and aldesleukin)
Patients receive trastuzumab IV over 30-90 minutes on days 1 and 8 and aldesleukin SC on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (trastuzumab and aldesleukin)
Patients receive trastuzumab IV over 30-90 minutes on days 1 and 8 and aldesleukin SC on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (trastuzumab and aldesleukin)
Patients receive trastuzumab IV over 30-90 minutes on days 1 and 8 and aldesleukin SC on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: trastuzumab (Biological)
Treatment (trastuzumab and aldesleukin)
Patients receive trastuzumab IV over 30-90 minutes on days 1 and 8 and aldesleukin SC on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: aldesleukin (Biological)
结局指标
主要结局
Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Up to 12 months
Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0
时间窗: Up to 12 months
次要结局
- Degree of NK cell expansion(Up to 12 months)
- Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells(Up to 12 months)