A Randomized, Open Label, Multicenter Phase IIIb Study Comparing Two Trastuzumab Dosing Regimens, Each in Combination With Cisplatin/Capecitabine Chemotherapy, as First-Line Therapy in Patients With HER2-Positive Metastatic Gastric or Gastro-Esophageal Junction Adenocarcinoma Who Have Not Received Prior Treatment for Metastatic Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 296
- 主要终点
- Overall Survival - FAS
研究概览
简要总结
This randomized, open-label, multicenter, international Phase IIIb study will compare the efficacy and safety of two Herceptin dosing regimens in combination with cisplatin/capecitabine chemotherapy in participants with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma. Participants who have not received prior treatment for metastatic disease will be randomized to receive Herceptin intravenously as either an 8-milligram per kilogram (mg/kg) loading dose followed by 6 mg/kg every 3 weeks (q3w) as standard of care or an 8-mg/kg loading dose followed by 10 mg/kg q3w until disease progression. Capecitabine will be administered for 6 cycles at a dose of 800 milligrams per meter-squared (mg/m^2) orally twice a day on Days 1 to 14 of each 3-week cycle, and cisplatin will be administered intravenously for 6 cycles at a dose of 80 mg/m^2 on Day 1 of each 3-week cycle. Herceptin will be continued until disease progression occurs.
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
- •Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least liver or lung or both
- •Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease
- •At least 2 organs involved in metastatic gastric tumor (including at least lung or liver or both) in addition to the site of primary tumor, where metastasis in distant lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as "organs" in this context
- •HER2-positive primary or metastatic tumor as assessed by central laboratory
- •Adequate renal function (creatinine clearance greater than equal to (≥) 45 milliliters per minute [mL/min])
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2
排除标准
- •Previous chemotherapy for locally advanced or metastatic disease
- •Prior gastrectomy (partial or total) for the underlying malignant disease under investigation
- •Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent
- •Residual relevant toxicity resulting from previous therapy
- •Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine
- •Current (significant or uncontrolled) gastrointestinal bleeding
- •Other malignancy within the last 5 years, except for carcinoma in situ of the cervix and basal or squamous cell carcinoma of the skin
- •History of documented congestive heart failure, angina pectoris requiring medication, electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly controlled hypertension, clinically significant valvular heart disease, or high-risk uncontrollable arrhythmias
- •Baseline left ventricular ejection fraction (LVEF) less than (<) 50%, documented by echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac magnetic resonance imaging (MRI)
- •Chronic or high-dose corticosteroid therapy
- •History or clinical evidence of brain metastases
- •Pregnant women
- •Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, or HIV-seropositive
研究组 & 干预措施
Capecitabine + Cisplatin + Herceptin (6 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Capecitabine (Drug)
Capecitabine + Cisplatin + Herceptin (6 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Cisplatin (Drug)
Capecitabine + Cisplatin + Herceptin (6 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Herceptin (Drug)
Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Capecitabine (Drug)
Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Cisplatin (Drug)
Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
干预措施: Herceptin (Drug)
结局指标
主要结局
Overall Survival - FAS
时间窗: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Percentage of Participants Who Died - FAS
时间窗: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.
次要结局
- Percentage of Participants Who Died - Per Protocol Set (PPS)(From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015))
- Overall Survival - PPS(From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015))
- Progression-Free Survival - PPS(From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015))
- Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS(Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days))
- Percentage of Participants With Disease Progression or Death - PPS(From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015))
- Percentage of Participants With Objective Response - PPS(From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015))
- Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS(Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days))