A Randomized, Open-label Study of the Effect of First-line Herceptin in Combination With a Fluoropyrimidine and Cisplatin Versus Chemotherapy Alone on Overall Survival in Patients With HER2-positive Advanced Gastric Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 584
- 主要终点
- Overall Survival - Time to Event
研究概览
简要总结
This parallel, randomized, open-label, multi-centre study will evaluate the effect on overall survival of trastuzumab (Herceptin) in combination with a chemotherapy compared to the chemotherapy alone in patients with HER2-positive advanced gastric cancer. Trastuzumab (Herceptin) will be administered as intravenous infusion of 6 mg/kg (loading dose 8 mg/kg) every 3 weeks. The chemotherapy consists of a combination of 6 cycles of fluorouracil (800 mg/m2/day intravenous infusion every 3 weeks) and cisplatin (80 mg/m2 intravenous infusion every 3 weeks), or capecitabine (Xeloda, 1000 mg/m2 po twice daily for 14 days every 3 weeks) and cisplatin (80 mg/m2 intravenous infusion every 3 weeks). Treatment with trastuzumab (Herceptin) will continue until disease progression. The target sample size is 300-600 patients.
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
- 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
- •Adult patients >=18 years of age
- •Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction
- •Adenocarcinoma
- •HER2-positive tumors
排除标准
- •Previous chemotherapy for advanced/metastatic disease
- •Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome
- •History of cardiac disease
- •Dyspnoea at rest, due to complications of advanced malignancy or other disease, or patients who require supportive oxygen therapy
研究组 & 干预措施
Trastuzumab, Fluoropyrimidine, Cisplatin
Participants received an initial loading dose of 8 milligrams per kilogram (mg/kg) trastuzumab i.v. on Day 1 of cycle, followed by 6 mg/kg i.v. every 3 weeks until disease progression; 800 mg/m2 fluorouracil i.v. on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Trastuzumab (Drug)
Trastuzumab, Fluoropyrimidine, Cisplatin
Participants received an initial loading dose of 8 milligrams per kilogram (mg/kg) trastuzumab i.v. on Day 1 of cycle, followed by 6 mg/kg i.v. every 3 weeks until disease progression; 800 mg/m2 fluorouracil i.v. on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Fluorouracil (Drug)
Trastuzumab, Fluoropyrimidine, Cisplatin
Participants received an initial loading dose of 8 milligrams per kilogram (mg/kg) trastuzumab i.v. on Day 1 of cycle, followed by 6 mg/kg i.v. every 3 weeks until disease progression; 800 mg/m2 fluorouracil i.v. on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Cisplatin (Drug)
Trastuzumab, Fluoropyrimidine, Cisplatin
Participants received an initial loading dose of 8 milligrams per kilogram (mg/kg) trastuzumab i.v. on Day 1 of cycle, followed by 6 mg/kg i.v. every 3 weeks until disease progression; 800 mg/m2 fluorouracil i.v. on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Capecitabine (Drug)
Fluoropyrimidine, Cisplatin
Participants received 800 milligrams per square meter (mg/m2) fluorouracil intravenous (i.v.) on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine orally (p.o.) twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Fluorouracil (Drug)
Fluoropyrimidine, Cisplatin
Participants received 800 milligrams per square meter (mg/m2) fluorouracil intravenous (i.v.) on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine orally (p.o.) twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Cisplatin (Drug)
Fluoropyrimidine, Cisplatin
Participants received 800 milligrams per square meter (mg/m2) fluorouracil intravenous (i.v.) on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine orally (p.o.) twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Overall Survival - Time to Event
时间窗: BL, Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
The median time, in months, from the date of randomization to the date of an OS event. Participants were censored at the last date tumor measurement, the last date in the study drug log, or the date of last follow-up.
Overall Survival (OS) - Percentage of Participants With an Event
时间窗: Baseline (BL), Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
OS was defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
次要结局
- Duration of Response - Percentage of Participants With an Event(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Time to Progression (TTP) - Percentage of Participants With an Event(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Percentage of Participants With Change From Baseline in Body Weight by Percentage Change in Weight(BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Steady State Trastuzumab Area Under the Concentration (AUC)(Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106)
- Trastuzumab Minimum Serum Concentration (Cmin)(Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106)
- Percentage of Participants With a Change in Analgesic Medication During the Study(BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Progression-Free Survival (PFS) - Percentage of Participants With an Event(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Duration of Response(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- European Organisation For the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C-30) Questionnaire Scores(BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Body Weight (Kilograms [kg]) at BL(BL)
- Progression-Free Survival - Time to Event(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Time to Progression - Time to Event(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores(BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Trastuzumab Maximum Serum Concentration (Cmax)(Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106)
- Percentage of Participants With Clinical Benefit(BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)
- Pain Intensity Scores as Assessed By Visual Analog Scale (VAS)(BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis)