ITACA-S2(Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma of the Stomach:Comparison of the Efficacy of a Peri-operative Versus a Post-operative Chemotherapy Treatment in Patients With Operable Gastric Cancer and Assessment of the Benefit of a Post-operative Chemo-radiotherapy.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1,180
- 试验地点
- 64
- 主要终点
- Overall survival (OS)- Timing Study
研究概览
简要总结
The study addresses two primary questions, according to its factorial design:
- to compare the efficacy in terms of overall survival (OS) of a peri-operative vs. a post-operative chemotherapy (CHT) treatment, irrespectively of the presence of a post-surgical chemo-radiotherapy (CHT-RTX) (Timing Study);
- to compare the efficacy in terms of relapse free survival (l-RFS) of a post-surgical CHT-RTX treatment vs. no other treatment, irrespectively of the timing of CHT (RTX Study).
The study has a 2x2 factorial design, thus consisting of two independent, following specific eligibility criteria and with different randomization scheme studies, the Timing Study and the RTX Study.
Both studies are Italian, multicentre, open-label, randomized, superiority, phase III trials conducted in patients with histologically confirmed, localized gastric adenocarcinoma, which is considered operable.
In the Timing Study patients fulfilling the eligibility criteria will be randomized with a 1:1 ratio to receive:
- peri-operative CHT (Arm A) or
- post-operative CHT (Arm B) Once randomized in the Timing Study, patients may also be randomized in the RTX
Study to receive in addition to CHT a post-operative CHT-RTX treatment or no other treatment. This is possible since the randomization will be done in two steps: the first for the Timing Study for all the participating centres (peri-operative CHT vs. post-operative CHT) and the second one for the RTX Study, only for those centres with the radiotherapist willing and able to participate (post- surgical CHT-RTX vs. no other treatment). Thus the following four arms will be generated:
- peri-operative CHT (Arm A)
- post-operative CHT (Arm B)
- peri-operative CHT + post-operative CHT-RTX (Arm C)
- post-operative CHT + post-operative CHT-RTX (Arm D) The study will be conducted in more than one hundred experimental centres. Follow-up F(-up) procedures and timing of the visits will be consistent with current clinical practice.
Based on case-mix of sample 1000-1180 patients are needed in the Timing study and 420-520 in the RTX study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- •age >18 years
- •Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1
- •T3 or T4 carcinoma without lymphnode involvement (N0) and any T-stage with (N+) lymphnode involvement
- •no distant metastases (M0)
- •fitness to receive CHT and CHT-RTX
- •no peripheral neuropathy greater than grade 1
- •absence of peritoneal carcinomatosis
- •written informed consents (one for each trial) given before the randomization, according to International Conference on Harmonisation/Good Clinical Practice (ICH/GCP)
排除标准
- •adenocarcinoma of the gastro-esophageal junction
- •previous CHT or RTX
- •abnormal haematological, hepatic or renal functions, assessed within 7 days prior to randomization
- •lymphnode metastases (biopsy proof, if possible) outside the loco-regional field, such as supraclavicular, mediastinal or para-aortic nodes
- •positive peritoneal cytology
- •clinical significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), instable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
- •lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication
- •history or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or patients at high risk from treatment complications
- •pregnancy or breast feeding. Women of childbearing potential and their parents must be willing to practice acceptable methods of birth control to prevent pregnancy
- •presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and f-up schedule
研究组 & 干预措施
peri-operative CHT (Arm A)
In peri-operative CHT arm CHT will be administered within 1 week (+3 days) after randomization, surgery will be performed after re-staging and 3+1 weeks after completion of the third cycle of CHT (approximately 13+1 weeks after randomization). Then CHT will be re-administered 5+1 weeks after surgery.
干预措施: peri-operative cht (Other)
post-operative CHT (Arm B)
In post-operative CHT arm, surgery will take place 3+1 weeks after randomization and CHT will be administered 5+1 weeks after surgery (approximately 8+1 weeks after randomization).
干预措施: post-operative CHT (Other)
peri-operative CHT + post-operative CHT-RTX (Arm C)
CHT 1 week (+3 days) after randomization surgery after re-staging and 3+1 weeks after completion of the third cycle of CHT CHT 5+1 weeks after surgery.
干预措施: peri-operative cht + post-operative cht-rtx (Other)
post-operative CHT + post-operative CHT-RTX (Arm D)
surgery will take place 3+1 weeks after randomization and CHT will be administered 5+1 weeks after surgery (approximately 8+1 weeks after randomization).
干预措施: post-operative cht + post-operative cht-rtx (Other)
结局指标
主要结局
Overall survival (OS)- Timing Study
时间窗: 5 years
OS, defined for each patient as the time from the date of randomization to the date of death from any cause. Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.
次要结局
- Dose-intensity(up to 8 weeks)
- Disease Free Survival (DFS) - Timing Study(3 years)
- Maximum toxicity grade(up to 8 weeks)
- Relapse Free Survival (l-RFS)- RTX Study(3 years)