Fusobacterium Nucleatum Eradication in Postoperative Stage II/III Colorectal Cancer(FINER-PACE)by Oral Metronidazole: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 294
- 试验地点
- 4
- 主要终点
- Disease Free Survival, DFS
研究概览
简要总结
Fusobacterium nucleatum (Fusobacterium nucleatum, Fn) has been identified as an independent risk factor for recurrence of colorectal cancer. In this study, oral metronidazole would be used to reduce the abundance of Fn in patients with high Fn, so as to explore whether oral metronidazole can improve the efficacy of postoperative chemotherapy in patients with colorectal cancer.
详细描述
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Previously in the investigators' research, the investigators find the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. The investigators found that Fusobacterium nucleatum (Fn) was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, the investigators' bioinformatic and functional studies demonstrated that Fn promoted colorectal cancer resistance to chemotherapy. Metronidazole has been known to treat with anaerobe infection, including Fusobacterium. So oral metronidazole would be used to reduce the abundance of Fn in patients with high Fn, so as to explore whether oral metronidazole can improve the efficacy of postoperative chemotherapy in patients with colorectal cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Individuals aged 18-75 years
- •Individuals firstly confirmed by surgery pathology as colorectal cancer (AJCC cancer staging II - III), who need mFOLFOX6 or CapeOX postoperative chemotherapy
- •Individuals with Fn - deltaCT value in colon tissue samples detected by qPCR ≥-12 before receiving chemotherapy
- •Individuals who could tolerate chemotherapy drugs: ECOG (Eastern Cooperative Oncology Group) score ≤2 points, WBC(White Blood Cell) ≥4.0×10^9/L, Hb （Hemoglobin） ≥80g/L, PLT （Platelet） ≥80×10^9/L, ALT （Alanine Aminotransferase）< 2ULN （Upper Limmit of Normal）, Scr （Creatinine）< 1.5ULN
- •Individuals who participate this study and sign the informed consent form willingly.
排除标准
- •Individuals with colorectal adenoma or non-colorectal cancer, such as inflammatory bowel disease
- •Individuals with a history of familial adenomatous polyposis (FAP)
- •Individuals with severe heart, lung, brain, kidney, gastrointestinal or systemic diseases
- •Individuals who used antibiotics for more than 5 days in 1 month prior to chemotherapy
- •Individuals with stage I or IV colorectal cancer, or with stage II colorectal cancer who do not need postoperative chemotherapy
- •Individuals with contraindications for metronidazole
- •Individuals who unwilling to participate this study，or unwilling to sign the informed consent form
- •Individuals with any conditions that the researchers considered inappropriate for inclusion
研究组 & 干预措施
Metronidazole
supplement of metronidazole 0.4g three times per day for 7 days, which is one treatment every 4 weeks for mFOLFOX6(6 treatments totally),and every 6 weeks for CapeOX (4 treatments totally).
干预措施: Metronidazole Oral Tablet (Drug)
Placebo
supplement of identical-appearing placebo 0.4g three times per day for 7 days, which is one treatment every 4 weeks for mFOLFOX6 (6 treatments totally),and every 6 weeks for CapeOX 4 treatments totally).
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Disease Free Survival, DFS
时间窗: 5 years
The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.
次要结局
- Overall Survival, OS(5 years)
- Recurrence Rate, RR(3 years, 5 years)
研究者
Jing-yuan Fang, MD, Ph. D
Director of Department of Gastroenterology
Shanghai Jiao Tong University School of Medicine