A Two-Cohort, Open-Label, Multicenter Study of Trastuzumab Emtansine (T-DM1) in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,185
- 试验地点
- 300
- 主要终点
- Percentage of Participants With Adverse Events of Primary Interest (AEPIs)
研究概览
简要总结
This two-cohort, open-label, multicenter study will assess the safety, efficacy and tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general participant population; Cohort 2 will include only Asian participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •HER2-positive disease determined locally
- •Histologically or cytologically confirmed invasive breast cancer
- •Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or metastatic setting must include both chemotherapy, alone or in combination with another agent, and an anti-HER2 agent, alone or in combination with another agent
- •Documented progression of incurable, unresectable, LABC, or mBC, defined by the investigator: progression must occur during or after most recent treatment for LABC/mBC or within 6 months of completing adjuvant therapy
- •Measurable and/or non-measurable disease
- •Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
- •Adequate organ function
- •Use of highly effective contraception as defined by the protocol
排除标准
- •History of treatment with trastuzumab emtansine
- •Prior enrollment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not
- •Peripheral neuropathy of Grade >/= 3 per National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 4.0
- •History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer
- •History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria
- •History of exposure to cumulative doses of anthracyclines
- •History of radiation therapy within 14 days of first study treatment. The participant must have recovered from any resulting acute toxicity (to Grade </=1) prior to first study treatment.
- •Metastatic central nervous system (CNS) disease only
- •Brain metastases which are symptomatic
- •History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
- •History of symptomatic CHF (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction or unstable angina within 6 months of first study treatment
- •Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy
- •Current severe, uncontrolled systemic disease (clinically significant cardiovascular, pulmonary, or metabolic disease)
- •Pregnancy or lactation
- •Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
- •History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product
研究组 & 干预措施
Trastuzumab Emtansine (All Participants)
This cohort will enroll all participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
干预措施: Trastuzumab Emtansine (Drug)
Trastuzumab Emtansine (Asian Participants)
This cohort will enroll Asian race participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
干预措施: Trastuzumab Emtansine (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events of Primary Interest (AEPIs)
时间窗: Baseline up to approximately 7 years
The AEPIs in this study were defined as the following: adverse events (AEs) Grade \>/= 3, specifically, hepatic events, allergic reactions, thrombocytopenia and hemorrhage events, all Grade \>/= 3 AEs related to trastuzumab emtansine and pneumonitis events of all grades.
次要结局
- Percentage of Participants With Specific AEPIs(Baseline up to approximately 7 years)
- Progression-Free Survival According to Response Evaluation for Solid Tumors (RECIST) Version (v) 1.1 As Per Investigator Assessment(Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years))
- Overall Survival(Baseline until death (up to approximately 7 years))
- Number of Hospital Visits(Baseline up to approximately 7 years)
- Time to Response According to RECIST v 1.1(Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years))
- Type of Hospital Visits(Baseline up to approximately 7 years)
- Percentage of Participants With Adverse Events of Special Interest (AESIs)(Baseline up to approximately 7 years)
- Percentage of Participants With Best Overall Response (Complete Response [CR] or Partial Response [PR]) According to RECIST v 1.1 As Per Investigator Assessment(Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years))
- Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD]) According to RECIST v 1.1(Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years))
- Duration of Response (DOR) According to RECIST v 1.1(Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years))