A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab+Herceptin+Docetaxel Versus Placebo+Herceptin+Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 243
- 试验地点
- 15
- 主要终点
- Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
研究概览
简要总结
This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
- •HER2-positive metastatic breast cancer (MBC)
- •Left ventricular ejection fraction (LVEF) greater than or equal to (>=) 55 percent (%) at baseline (within 42 days of randomization)
- •Eastern Cooperative Oncology Group Performance Status of 0 or 1
- •Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab)
排除标准
- •History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
- •History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
- •History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (<) 12 months
- •History of persistent Grade >= 2 hematologic toxicity resulting from previous adjuvant therapy
- •Grade >= 3 peripheral neuropathy at randomization
- •History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent
- •Current clinical or radiographic evidence of central nervous system (CNS) metastases
- •History of exposure to cumulative doses of anthracyclines
- •Current uncontrolled hypertension or unstable angina
- •History of congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction within 6 months of randomization
- •History of LVEF decrease to < 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- •Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
- •Inadequate organ function within 28 days prior to randomization
- •Current severe, uncontrolled systemic disease
- •Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- •Pregnant or lactating women
- •History of receiving any investigational treatment within 28 days of randomization
- •Current known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or active hepatitis B virus (HBV)
- •Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization
- •Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
- •Known hypersensitivity to any of the protocol-specified study treatments
- •Concurrent participation in an interventional or noninterventional study
研究组 & 干预措施
Arm A: Placebo + Trastuzumab + Docetaxel
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Arm A: Placebo + Trastuzumab + Docetaxel
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Placebo (Drug)
Arm A: Placebo + Trastuzumab + Docetaxel
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Trastuzumab (Drug)
Arm B: Pertuzumab + Trastuzumab + Docetaxel
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Arm B: Pertuzumab + Trastuzumab + Docetaxel
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Pertuzumab (Drug)
Arm B: Pertuzumab + Trastuzumab + Docetaxel
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
时间窗: From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day).
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1
时间窗: At 1, 2, and 3 years
Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median \[range\] time on study for Arm A vs. Arm B was 145.29 \[3.3-225.3\] weeks vs. 174.79 \[0.9-226.1\] weeks.
次要结局
- Overall Survival(From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks))
- Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years(At 1, 2, and 3 Years)
- Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1(At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks))
- Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1(From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks))
- Number of Participants With at Least One Adverse Event(From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months))
- Number of Participants With at Least One Grade ≥3 Adverse Event(From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months))
- Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment(From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months))
- Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan(From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months))
- Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan(From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months))
- Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans(Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years)
- Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study(Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months))