A Phase II, Single-Arm, Open-Label Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 主要终点
- Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review
研究概览
简要总结
Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
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
- •Signed study-specific Informed Consent Form(s)
- •Age ≥ 18 years
- •Histologically documented breast cancer
- •HER2-positive disease
- •Metastatic breast cancer
- •Disease progression on the last chemotherapy regimen received in the metastatic setting
- •Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and capecitabine in the neoadjuvant, adjuvant, locally advanced, or metastatic setting and prior treatment with at least two lines of therapy (a line of therapy can be a combination of two agents or single-agent chemotherapy) in the metastatic setting
- •At least two lines of anti-HER2 therapy must have been given in the metastatic setting as monotherapy or combined with chemotherapy or hormonal therapy. The HER2-targeted agent can include trastuzumab, lapatinib, or an investigational agent with HER2-inhibitory activity.
- •A minimum of 6 weeks of trastuzumab for the treatment of metastatic disease is required
- •Patients must have had at least 14 days of exposure in the metastatic setting to lapatinib and capecitabine (given together or separately) unless they were intolerant of lapatinib and/or capecitabine
排除标准
- •Chemotherapy ≤ 21 days before enrollment
- •Trastuzumab ≤ 21 days before enrollment
- •Hormone therapy ≤ 7 days before enrollment
- •Granulocyte-stimulating agent < 14 days before enrollment
- •Investigational therapy ≤ 28 days before enrollment
- •Previous radiotherapy for treatment of metastatic breast cancer ≤ 21 days before enrollment
- •Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 3 months of the first study treatment
- •History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins
- •History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; Epirubicin > 900 mg/m^2; Mitoxantrone > 120 mg/m^2 and idarubicin > 90 mg/m^2
- •Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
- •History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- •Current unstable angina
- •History of symptomatic congestive heart failure (CHF), or ventricular arrhythmia requiring treatment
- •History of myocardial infarction within 6 months of enrollment
- •Left ventricular ejection fraction (LVEF) < 50% within 28 days of enrollment
- •History of decreased LVEF to < 50% or symptomatic CHF with previous adjuvant trastuzumab treatment
- •Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy
- •Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
- •Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment
- •Current pregnancy or lactation
- •Current known infection with human immunodeficiency virus (HIV), active hepatitis B, and/or hepatitis C virus
- •Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
研究组 & 干预措施
Trastuzumab emtansine
Trastuzumab emtansine (T-DM1) was administered to participants at a dose of 3.6 mg/kg by intravenous (IV) infusion every 3 weeks until documented disease progression, unmanageable toxicity, or study termination.
干预措施: Trastuzumab emtansine [Kadcyla] (Drug)
结局指标
主要结局
Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review
时间窗: From randomization until the primary analysis data cut-off date of September 2009 (6 months after last patient enrolled) and until the final efficacy analysis cut-off date of 1 January 2010 (approximately 9 months after the last patient enrolled).
Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive occasions ≥ 4 weeks apart, assessed using Response Evaluation Criteria in Solid Tumors (RECIST). CR: the disappearance of all target lesions and all nontarget lesions and normalization of tumor marker level and no new lesions. PR: disappearance of all target lesions and persistence of ≥ 1 nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing nontarget lesions. The primary data cut-off date was 17 September 2009 (approximately 6 months after the last patient was enrolled). The final efficacy analysis was performed using a data cut-off date of 1 January 2010 (approximately 9 months after the last patient was enrolled).
次要结局
- Percentage of Participants With Clinical Benefit Based on Investigator Assessment(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Duration of Objective Response as Assessed Through Independent Radiologic Review(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Percentage of Participants With Clinical Benefit Based on Independent Radiologic Review(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Progression-free Survival as Assessed Through Independent Radiologic Review(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Progression-free Survival Based on Investigator Assessment(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Duration of Objective Response Based on Investigator Assessment(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)
- Objective Response Based on Investigator Assessment(From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.)