FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 326
- 试验地点
- 1
- 主要终点
- Progression-Free Survival
研究概览
简要总结
Patients with metastatic adenocarcinoma of the stomach or the esophagogastric junction (II-III type by Siewert) without previous therapy will be treated with one of two chemotherapy combinations . One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin (FOLFOX6), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Irinotecan (mFOLFIRINOX). Main objective of the study is progression free survival.
详细描述
This parallel, randomized, open-label study 326 patients with metastatic ( adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After randomization patients receive 9 cycles FOLFOX6 or mFOLFIRINOX.
Stratification factors include ECOG, site of metastasis, age, pathological subtypes.
Efficacy will be evaluated every 3 cycles with RECIST. Toxicity will be assessed with WHO CTC 3.0 every 2 weeks.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of the esophagogastric junction (Siewert type II-III) or the stomach
- •no prior palliative chemotherapy or radiation therapy
- •Age 18-70 years (female and male)
- •Eastern Cooperative Oncology Group ≤ 2
- •Neutrophils> 2.000/µl
- •Platelets > 100.000/µl
- •Normal value of Serum Creatinin
- •Albumin level > 29 г/л
- •Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper limits of normal (ULN)
- •Total Bilirubin less than 1.5 times the ULN
- •Written informed consent.
排除标准
- •Previous palliative cytostatic chemotherapy
- •Cancer relapse
- •Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia IV)
- •Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse Events (CTCAE) version 4.1;
- •Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, irinotecan
- •Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan or Docetaxel
- •Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV according to New York Heart Association (NYHA)
- •Severe non-surgical accompanying disease or acute infection (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors and others)
- •Malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- •Peripheral polyneuropathy > Grad II
- •Liver dysfunction (AST)/ALT>3,0xULN, ALT>3xULN, Bilirubin>1,5xULN) Serum Creatinin >1,0xULN
- •Chronic inflammable gastro-intestinal disease
- •Inclusion in another clinical trial
- •Pregnancy or lactation
- •Hepatitis B or C in the active stage
- •Human immunodeficiency virus(HIV) infected
- •Serious concomitant somatic and mental illnesses / deviations or territorial causes that may prevent the patient from participating in the protocol and observing the protocol schedule
- •Foreigners or persons with limited legal status
研究组 & 干预措施
FOLFOX6
5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: Oxaliplatin (Drug)
FOLFOX6
5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: Leucovorin (Drug)
FOLFOX6
5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: 5-FU (Drug)
mFOLFIRINOX
Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: Irinotecan (Drug)
mFOLFIRINOX
Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: Oxaliplatin (Drug)
mFOLFIRINOX
Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: 5-FU (Drug)
mFOLFIRINOX
Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
干预措施: Leucovorin (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: 36 months
PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. 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
- Overall Survival (OS)(60 months)
- Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)(12 months)
- Duration of Response(12 months)
- Treatment associated toxicities(12 months)