Phase III Study of Neoadjuvant FOLFOXIRI Chemotherapy Versus Immediate Surgery for High-risk Resectable Stage II and III Colon Cancers
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 840
- 试验地点
- 1
- 主要终点
- Disease-free survival
研究概览
简要总结
BACKGROUND:
In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer.
OBJECTIVE:
The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.
详细描述
This trial is a a two-arm, multicenter, open labelled, prospective, randomized phase III studies. Eligible patients with High-risk Resectable Stage II and III (T4 or T3 with extramural depth≧5 mm) colon cancer patients will be randomly assigned, in a 2:1 ratio, to receive either perioperative or postoperative chemotherapy.
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 proven adenocarcinoma or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer of the colon(≥ 12 cm from the anal verge).
- •pMMR in immunohistochemical detection or MSI-H in MSI test.
- •Determined preoperatively by either spiral or multidetector CT: high risk T3 (tumor disruption of muscle wall and extension into pericolic fat with more than 5 mm protrusion into adjacent mesenteric fat) or T4 (tumor penetrates to the surface of the visceral peritoneum or directly invades or is adherent to adjacent organs or structures).
- •Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
- •Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
- •Adequate renal biochemistry: serum creatinine was less than 1.5 times the normal value.
- •Adequate hepatobiliary function: serum total bilirubin and ALT were less than 1.5 times the normal value.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Any patient for whom radiotherapy is advised by the MDT
- •Strong evidence of distant metastases or peritoneal nodules (M1)
- •dMMR in immunohistochemical detection or MSI-L/MS-S in MSI test.
- •Peritonitis (secondary to perforated tumour)
- •Colonic obstruction that has not been defunctioned
- •Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
- •Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
- •Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
研究组 & 干预措施
Neoadjuvant chemotherapy
12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy
干预措施: neoadjuvant chemotherapyI (Drug)
Neoadjuvant chemotherapy
12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy
干预措施: Colectomy (Procedure)
Postoperative chemotherapy
surgery followed by 24 weeks of FOLFOX or CapeOX or Cape
干预措施: Colectomy (Procedure)
Postoperative chemotherapy
surgery followed by 24 weeks of FOLFOX or CapeOX or Cape
干预措施: adjuvant chemotherapy (Drug)
结局指标
主要结局
Disease-free survival
时间窗: 2 years
Defined as the time from randomization to relapse or death, whichever occurred first
次要结局
- Surgical morbidity(30 days post surgery)
- CT staging(from randomization to surgery completed, up to 6 months)
- Overall survival(5 years)
- Down-staging of primary tumors(1 year)
- Chemotherapy toxicity(through chemotherapy administration, up to 6 months)
- R0 resection rate(after surgery completed, up to 1 month)
- CT assessment of response to neoadjuvant treatment(up to 6 months)
研究者
Pei-Rong Ding
Professor
Sun Yat-sen University