Total Neoadjuvant Chemotherapy With 5-fluoruracil, Leucovorin, Oxaliplatin, and Docetaxel in Locally Advanced Gastric and Gastroesophageal Junction Cancer (OCTASUR): Randomized, Multi-center, Open-label Trial, Phase 2/3
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- All 8 planned FLOT cycles tolerance rate.
研究概览
简要总结
The main goal of this study is to investigate the proportion of participants with locally advanced gastric and gastroesophageal adenocarcinoma without previous treatment during the last 5 years who can tolerate all planned cycles of chemotherapy and radical surgical treatment who will be prospectively randomized into two groups to undergo one of two chemotherapy regimens, followed by surgery:
- 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin, and Docetaxel (FLOT) followed by surgery.
- 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT cycles postoperatively.
详细描述
This is a multi-center international European prospective randomized study that aims to enroll participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3) adenocarcinoma (≥cT3 and/or ≥cN0 and M0) with no history of previous oncological treatment during the last five years, who will be included in this study after reading and signing the informed consent. After the initial diagnostic laparoscopy, patients will be randomized into two groups in a 1:1 ratio, with allocation to one of the two study groups.
Patients randomized to the first (control) group will receive eight cycles of the perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and four cycles after surgical intervention. Patients randomized to the second (study) group will receive eight cycles of FLOT total neoadjuvant chemotherapy, followed by surgery.
The study's primary endpoint is the proportion of patients receiving all planned chemotherapy cycles and radical surgical treatment. Secondary endpoints are perioperative morbidity and mortality (surgical and chemotherapeutic complications); disease-free survival (DFS) and 1-, 3- and 5-years overall survival (OS); quality of life during and after the treatment; correlation between the pathohistological response and chemotherapy regimen; composition and biomarkers of gut microbiota; objective tumor response.
Based on previous studies, with the current standard treatment protocol-four cycles of FLOT chemotherapy before surgery and four cycles after-only 47% of patients complete all eight cycles. In contrast, with total neoadjuvant therapy, where the entire chemotherapy regimen is administered before surgery, 71% of patients are able to complete all eight FLOT cycles.
Given these findings, it was calculated that to ensure 80% study power with a two-sided 5% significance level, each study group should include 65 participants. Considering an expected dropout rate of 15%, a total of 150 patients will be recruited. Up to 40 patients will be enrolled in Vilnius, Lithuania, with the remaining participants recruited in Kyiv, Ukraine.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Tumor spread according to TNM: ≥cT3 and/or ≥cN0 and M0 (except of invasion of the common hepatic artery, celiac trunk, proximal part of the splenic artery, aorta, head of the pancreas);
- •Performance status by Eastern Cooperative Oncology Group (ECOG): 0 - 1;
- •Histologically confirmed gastric adenocarcinoma or gastroesophageal junction (Siewert type 2/3) adenocarcinoma.
- •Differentiation grade: G0 - G4;
- •Tumor localization: cardio-esophageal junction (Siewert 2, 3), cardiac part of the stomach, body of the stomach, antral part of the stomach, pyloric part of the stomach;
- •Tumor extension: esophagus, diaphragm, liver, body and tail of the pancreas, anterior abdominal wall, small and large intestine, distal part of the splenic artery, spleen;
- •Patient agrees to participate in this biomedical study.
排除标准
- •Presence of another oncological disease at a different site if less than 5 years have passed since radical treatment.
- •Comorbidities or patient conditions that preclude the administration of chemotherapy.
研究组 & 干预措施
Perioperative 4+4 FLOT cycles
4 cycles of neoadjuvant FLOT chemotherapy regimen, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy regimen.
干预措施: Docetaxel (Drug)
Perioperative 4+4 FLOT cycles
4 cycles of neoadjuvant FLOT chemotherapy regimen, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy regimen.
干预措施: Oxaliplatin (Drug)
Perioperative 4+4 FLOT cycles
4 cycles of neoadjuvant FLOT chemotherapy regimen, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy regimen.
干预措施: Leucovorin (Drug)
Perioperative 4+4 FLOT cycles
4 cycles of neoadjuvant FLOT chemotherapy regimen, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy regimen.
干预措施: Fluorouracil (Drug)
Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
8 cycles of total neoadjuvant FLOT chemotherapy regimen, followed by surgery.
干预措施: Docetaxel (Drug)
Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
8 cycles of total neoadjuvant FLOT chemotherapy regimen, followed by surgery.
干预措施: Oxaliplatin (Drug)
Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
8 cycles of total neoadjuvant FLOT chemotherapy regimen, followed by surgery.
干预措施: Leucovorin (Drug)
Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
8 cycles of total neoadjuvant FLOT chemotherapy regimen, followed by surgery.
干预措施: Fluorouracil (Drug)
结局指标
主要结局
All 8 planned FLOT cycles tolerance rate.
时间窗: From enrollment to the end of treatment at 12 weeks
The proportion of patients receiving all planned cycles of chemotherapy and radical surgical treatment.
次要结局
- Chemotherapy toxicity rate and profile.(At the end of each FLOT cycle (each cycle is 14 days), up to 14 days after the last cycle.)
- Surgical complications rate.(30 days after surgery.)
- Median overall survival.(From the start of treatment to the patient's death or the end of follow-up - 5 years follow-up after the last intervention.)
- Progression-free survival.(Calculated as the time from the start of treatment to disease progression or the end of follow-up at 5 years after the treatment completion.)
- Quality of patients' life.(24 months.)
- Correlation between the pathohistological response and overall and disease-free survival.(21 days after surgery.)
- Histopathological tumor response rate (Becker regression criteria).(21 days after surgery)
- Intestinal microbiome composition.(Within 7 days before the start of the treatment.)
- Objective tumor response.(From within 7 days before the first chemotherapy course and until 4 weeks before the surgical intervention.)
研究者
Mykyta Pepenin
MD
Ukrainian Society of Clinical Oncology