INtegratioN of Trastuzumab, With or Without Pertuzumab, Into periOperatiVe chemotherApy of HER-2 posiTIve stOmach caNcer: the INNOVATION-TRIAL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 172
- 试验地点
- 45
- 主要终点
- Near Complete Pathological Response Rate
研究概览
简要总结
The purpose of this study is to find out whether either trastuzumab or the combination of trastuzumab and pertuzumab with standard chemotherapy shows more activity against gastro-oesophageal adenocarcinoma than standard chemotherapy given before and after surgery and it can be safely administered.
详细描述
This is a randomized phase II trial with an internal control. The randomization will be a 1:2:2 randomization (control: experimental arm 1: experimental arm 2). Potentially eligible patients will be screened centrally for the HER-2 status. After confirmation of HER-2 positive disease, eligible patients will be centrally randomized through the EORTC randomization system. A minimization technique will be used for random treatment allocation between the three treatment arms. Stratification will be done by histological subtype (intestinal/non-intestinal); Korea versus Europe; stage II versus III; node positive versus node negative.
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 proven, gastric or gastroesophageal (GE)-junction adenocarcinoma (Siewert I-III)
- •Patient medically fit for gastrectomy/oesophagogastrectomy as decided by the investigator
- •Age ≥ 18 years
- •WHO performance status 0 - 1
- •HER-2 overexpression
- •Amenable to gastrectomy/oesophagectomy
- •The cardiac ejection fraction (LVEF), as determined by echocardiography, multiple gated acquisition scan (MUGA) or cardiac MRI should be at least 50 %
- •Adequate organ function
- •written informed consent
- •For women who are not postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last treatment dose
- •For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods for contraception.
排除标准
- •Absence of distant metastases on CT scan of thorax and abdomen
- •prior chemo- or antibody therapy
- •history of significant cardiac disease
- •current uncontrolled hypertension
- •known hypersensitivity to the components of trastuzumab, pertuzumab, cisplatin, 5-follow-up or capecitabine
- •known dihydropyrimidine dehydrogenase (DPD) deficiency
- •ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine
- •chronic treatment with high-dose intravenous corticosteroids
- •previous malignancy within the last 5 years, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated cancer without impact on the patient's overall prognosis according to the judgment of the investigator.
- •psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •pregnant or breast feeding
研究组 & 干预措施
Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
干预措施: Pertuzumab (Drug)
Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
干预措施: gastrectomy (Procedure)
Standard chemotherapy
Cisplatin/capecitabine or cisplatin/5-fluorouracil
干预措施: Cisplatin (Drug)
Standard chemotherapy
Cisplatin/capecitabine or cisplatin/5-fluorouracil
干预措施: 5-fluorouracil or Capecitabine (Drug)
Standard chemotherapy
Cisplatin/capecitabine or cisplatin/5-fluorouracil
干预措施: gastrectomy (Procedure)
Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
干预措施: Cisplatin (Drug)
Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
干预措施: 5-fluorouracil or Capecitabine (Drug)
Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
干预措施: Trastuzumab (Drug)
Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
干预措施: gastrectomy (Procedure)
Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
干预措施: Cisplatin (Drug)
Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
干预措施: 5-fluorouracil or Capecitabine (Drug)
Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Near Complete Pathological Response Rate
时间窗: After 3 cycles (21 days) of neoadjuvant chemotherapy
To increase the major pathological response rate (\< 10% vital tumor cells) to neoadjuvant treatment by integrating both trastuzumab and pertuzumab into perioperative chemotherapy for HER-2 positive, resectable gastric cancer.
次要结局
- Locoregional failure(At the time of surgery and at 5 years)
- R0 resection rate(At the time of surgery)
- Progression-free survival(5 years after LPI)
- Overall survival(5 years after LPI)
- Distant failure(At the time of surgery and at 5 years)
- Toxicity(5 years after LPI)
- Recurrence-free survival(5 years after LPI)