A Randomized, Open-Label, Multicenter, Controlled Phase III Trial Comparing Neoadjuvant Chemoradiotherapy Followed by Surgery and Adjuvant Chemotherapy Versus Neoadjuvant Chemotherapy Followed by Surgery and Adjuvant Chemotherapy in Patients With Locally Advanced Gastric Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 620
- 试验地点
- 1
- 主要终点
- Disease-free Survival
研究概览
简要总结
Patients with histologically confirmed gastric adenocarcinoma with locally advanced gastric cancer are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy or neoadjuvant chemotherapy alone using XELOX regimen following D2 gastrectomy and adjuvant chemotherapy for 3 cycles. The primary end point is 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, pathological complete remission (pCR) and treatment safety.
详细描述
Background: Literatures have shown that patients with locally advanced gastric cancer could potentially benefit from neoadjuvant chemoradiotherapy, but whether this can improve patients' outcome is still unclear.
Patients and methods: In this study , patients with histologically confirmed gastric adenocarcinoma with pre-operative staging are cT3N2/N3M0, cT4aN+M0 and cT4bNanyM0, aged between 18-75 years old, with adequate organ function and having an Eastern Cooperative Oncology Group performance status score ≤2, are randomized in a 1:1 ratio to receive neoadjuvant chemoradiotherapy with DT45Gy/25f plus three cycles of XELOX therapy [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy)] or neoadjuvant chemotherapy alone using XELOX regimen (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following by D2 gastrectomy and adjuvant chemotherapy with same dosage of XELOX therapy for up to 3 cycles. The primary end point is 3-year disease free survival (DFS), and secondary end point is 5-year overall survival (OS), R0 resection rate, pathological complete remission (pCR) and treatment safety. The final study analytics are to be conducted at the end of the 5th year after the last patient's enrollment.
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
- 否
入选标准
- •Histologically confirmed gastric cancer with clinical staging determined by endoscopic ultrasound and contrast-enhanced CT or MRI as cT3N2/N3M0, cT4aN+M0, or cT4bNanyM
- •Good general condition, with Eastern Cooperative Oncology Group (ECOG) performance status <2 and no contraindications to surgery.
- •Ambulatory male or female patients aged 18 to 75 years.
- •Sufficient physical fitness and organ function to tolerate major abdominal surgery.
- •Baseline laboratory parameters meeting the following criteria: WBC > 4.0 × 10⁹/L, ANC > 1.5 × 10⁹/L, Hb ≥ 100 g/L, PLT ≥ 100 × 10⁹/L, total bilirubin ≤ 1.5 × upper limit of normal (ULN), AST and ALT ≤ 2.5 × ULN, and serum creatinine ≤ 1.0 × ULN.
- •No prior or concurrent diagnosis of other malignancies.
- •Willing and able to comply with study protocol requirements during the trial period.
- •Provided written informed consent prior to screening, with full awareness of the right to withdraw from the study at any time without consequence.
- •Estimated life expectancy of at least 3 months.
排除标准
- •Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
- •Receipt of any antitumor therapy prior to surgery.
- •History of or concurrent malignancies other than gastric cancer.
- •Presence of psychiatric disorders, brain metastases, or leptomeningeal metastases.
- •Uncontrolled or severe comorbid conditions or active infections.
- •Decompensated dysfunction of major organs (e.g., cardiac, pulmonary, hepatic, or renal failure).
- •Concurrent participation in another clinical trial.
- •Contraindications to chemotherapy, radiotherapy, or surgery.
- •Active hepatitis B or hepatitis C virus infection.
- •Grade ≥2 peripheral neuropathy (per NCI-CTCAE).
- •Chronic intestinal diseases or short bowel syndrome.
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Known hypersensitivity to capecitabine or any of its excipients.
- •Ongoing treatment with sorivudine or related analogs.
- •Deemed unsuitable for participation in this clinical trial by the investigator.
研究组 & 干预措施
Neoadjuvant Chemoradiotherapy
Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy) ] following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: Neoadjuvant Chemoradiotherapy (Radiation)
Neoadjuvant Chemoradiotherapy
Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy) ] following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: R0 D2 Gastrectomy (Procedure)
Neoadjuvant Chemoradiotherapy
Radiotherapy (45Gy/25f) + 3 cycles of XELOX Chemotherapy [Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle (non-concurrent); Oxaliplatin 100 mg/m² IV on Day 1 + Capecitabine 825 mg/m² orally BID on Days 1-14 of a 21-day cycle (concurrent chemoradiotherapy) ] following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: Adjuvant Chemotherapy (Drug)
Neoadjuvant Chemotherapy
3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: Neoadjuvant Chemotherapy (Drug)
Neoadjuvant Chemotherapy
3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: R0 D2 Gastrectomy (Procedure)
Neoadjuvant Chemotherapy
3 cycles of XELOX Chemotherapy (Oxaliplatin 130 mg/m² IV on Day 1 + Capecitabine 1000 mg/m² orally BID on Days 1-14 of a 21-day cycle) following with D2 Gastrectomy and 3 cycles of Adjuvant XELOX Chemotherapy
干预措施: Adjuvant Chemotherapy (Drug)
结局指标
主要结局
Disease-free Survival
时间窗: 3 years
3-year DFS
次要结局
- Overall Survival(5 years)
- Pathological Complete Remission(Peri-operative period)
- Radical Resection Rate(Peri-operative period)
- Adverse effects(Peri-operative period)
研究者
Zhou Zhiwei
Director of Gastric Surgery
Sun Yat-sen University