A Double-Blind, Placebo-Controlled, Randomized, Multicenter Phase III Study Evaluating the Efficacy and Safety of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction and Gastric Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 780
- 试验地点
- 172
- 主要终点
- Overall Survival
研究概览
简要总结
This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg] intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
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 confirmed metastatic adenocarcinoma of the stomach or GEJ
- •Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Life expectancy greater than equal to (>/=) 3 months
排除标准
- •Previous cytotoxic chemotherapy for advanced (metastatic) disease
- •Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
- •Previous treatment with any HER2-directed therapy, at any time, for any duration
- •Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
- •Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities)
- •History or evidence of brain metastases
- •Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0])
- •Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted
- •Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
- •Inadequate hematologic, renal or liver function
- •Pregnant or lactating women
- •History of congestive heart failure of any New York Heart Association (NYHA) criteria
- •Angina pectoris requiring treatment
- •Myocardial infarction within the past 6 months before the first dose of study drug
- •Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
- •History or evidence of poorly controlled hypertension
- •Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)
- •Any significant uncontrolled intercurrent systemic illness
- •Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
研究组 & 干预措施
Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: 5-Fluorouracil (Drug)
Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Capecitabine (Drug)
Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Cisplatin (Drug)
Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Pertuzumab (Drug)
Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Trastuzumab (Drug)
Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: 5-Fluorouracil (Drug)
Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Capecitabine (Drug)
Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Cisplatin (Drug)
Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Placebo (Drug)
Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Overall Survival
时间窗: From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)
Overall survival (OS) was defined as the time from randomization to death from any cause. For participants who were still alive on the date of clinical data cut-off for the OS analysis, the last date when the participant was known to be alive on, or prior to the clinical cut-off date, was used to determine the censoring date. Participants who did not have any post-baseline data (e.g., dosing records, imaging dates, visit dates) were censored at the date of randomization plus 1 day.
次要结局
- Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria(Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months))
- Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria(Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months))
- Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria(Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months))
- Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria(Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months))
- Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria(Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months))
- Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03(From Baseline until end of post-treatment follow-up (up to 70 months))
- Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)(From Baseline until end of post-treatment follow-up (up to 70 months))
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score(Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years))
- Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score(Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years))
- Maximum Serum Concentration (Cmax) of Pertuzumab(Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days))
- Cmax of Trastuzumab(Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days))
- Minimum Serum Concentration (Cmin) of Pertuzumab(Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days))
- Cmin of Trastuzumab(Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days))