NCT00943670已完成2 期
A Phase II, Open-Label Study to Evaluate Corrected QT Interval Effects of Trastuzumab-MCC-DM1 (T-DM1) in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer and to Evaluate the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression While Receiving T-DM1 Alone
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 主要终点
- Change From Baseline in Mean Duration of the QTc Interval
研究概览
简要总结
This is a multicenter, open-label, single-arm Phase II study designed to evaluate the effect of T-DM1 on the duration of corrected QT (QTc) interval in patients with HER2-positive locally advanced or metastatic breast cancer and to make preliminary assessments regarding the safety, tolerability, and efficacy of combined T-DM1 and pertuzumab in patients with early disease progression.
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated using Fridericia's correction; the QTcB interval is the QT interval as calculated using Bazett's correction.
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
- •Histologically documented, locally advanced, or metastatic breast cancer; measurable and/or non-measureable but evaluable disease is permitted
- •HER2-positive disease
- •History of prior trastuzumab therapy
- •Life expectancy ≥ 90 days as assessed by the investigator
- •Negative urine pregnancy test ≤ 72 hours prior to Cycle 1 Day 1 for all women of childbearing potential
- •For patients of childbearing potential, agreement to use one highly effective form of contraception or two effective forms of contraception for the duration of the study treatment(s) and for 4 months after the last dose of T-DM1 or 6 months after the last dose of pertuzumab, if applicable
排除标准
- •Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 2 weeks of the first study treatment
- •Prior T-DM1 or pertuzumab therapy
- •History of intolerance (such as Grade 3-4 infusion reaction) and/or adverse events related to trastuzumab
- •Grade ≥ 2 (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v3) peripheral neuropathy at the time of or within 3 weeks prior to the first study treatment
- •Brain metastases that are untreated or progressive or have required any type of therapy, including radiation, surgery, and/or steroids, to control symptoms from brain metastases within 60 days prior to the first study treatment
- •History of cardiac disease, unstable angina, symptomatic congestive heart failure (CHF) (Class ≥ II per the New York Heart Associate [NYHA] guidelines), myocardial infarction, or ventricular arrhythmia ≤ 6 months prior to Cycle 1, Day 1
- •Implantable pacemaker or automatic implantable cardioverter defibrillator
- •Congenital long QT syndrome or family history of long QT syndrome
- •Current uncontrolled hypertension
- •Current treatment with medications that alter cardiac conduction (e.g., digitalis, beta-blockers, or calcium channel blockers) or medications that are generally accepted to have a risk of causing torsades de pointes (TdP)
- •Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
- •Major surgical procedure or significant traumatic injury within 28 days prior to first study treatment, or anticipation of the need for major surgery during the course of study treatment
结局指标
主要结局
Change From Baseline in Mean Duration of the QTc Interval
时间窗: Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QTcF intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcF interval was subtracted from the average QTcF intervals to create a baseline-adjusted average QTcF interval.
次要结局
- Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Change From Baseline in Uncorrected QT Interval(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Change From Baseline in PR Interval(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Change From Baseline in QRS Duration(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Change From Baseline in Heart Rate(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Percentage of Participants Within Each Absolute QTc Interval Category(Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Percentage of Participants Within Each Baseline-adjusted QTc Interval Category(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Percentage of Participants With New Abnormal U Waves(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Percentage of Participants With New Abnormal T Waves(Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.)
- Percentage of Participants With an Objective Response During the Single-agent Trastuzumab Emtansine Treatment Period(Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).)
- Duration of Objective Response Based on Investigator Assessment During the Single-agent Trastuzumab Emtansine Treatment Period(Time from the first documented objective response to the time of first documented disease progression or death, up to a maximum time period of one year.)
- Progression-free Survival During the Single-agent Trastuzumab Emtansine Treatment Period(From the first day of study treatment to the first documented disease progression or death, up to a maximum time period of one year.)
- Percentage of Participants With Clinical Benefit During the Single-agent Trastuzumab Emtansine Treatment Period(Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).)
- Number of Participants With Adverse Events (AEs)(From first dose until 30 days after last dose (up to 1 year).)
- Number of Participants With Decreased Ejection Fraction(Assessed at Baseline and after every 3 cycles, up to 1 year.)
- Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab(Blood samples were collected prior to dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
- Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
- Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity for T-DM1 and Total Trastuzumab(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycle 1.)
- Terminal Half-life for T-DM1 and Total Trastuzumab(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
- Clearance T-DM1 and Total Trastuzumab(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
- Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
- Number of Participants With Anti-therapeutic Antibodies (ATAs) to Trastuzumab Emtansine(Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.)
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