Colorectal Cancer Stage II, Colorectal Cancer Stage III
Conditions
Keywords
Metronidazole, Gut Microbiota, Postoperative Chemotherapy, Colorectal Cancer, Fusobacterium nucleatum
Brief summary
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.
Detailed description
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.
Interventions
DRUGMetronidazole Oral Tablet
Supplement of metronidazole 0.4g three times per day for 7 days before each two cycles of chemotherapy (mFOLFOX6 once every 4 weeks, CapeOX once every 6 weeks), which is 6 treatments for mFOLFOX6 and 4 treatments for CapeOX totally.
DRUGPlacebo oral tablet
Supplement of placebo oral tablet 0.4g three times per day for 7 days before each two cycles of chemotherapy (mFOLFOX6 once every 4 weeks, CapeOX once every 6 weeks), which is 6 treatments for mFOLFOX6 and 4 treatments for CapeOX totally.
Sponsors
Shanghai Municipal Commission of Health and Family Planning
Ruijin Hospital
Fudan University
Shanghai Zhongshan Hospital
Shanghai Shenkang Hospital Development Center
Shanghai Jiao Tong University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival, DFS | 5 years | The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival, OS | 5 years | The time from the initial surgical treatment of colorectal cancer to death from any cause. |
| Recurrence Rate, RR | 3 years, 5 years | Percentage of patients who has recurrence during or after chemotherapy with Metronidazole or Placebo. |
Countries
China
Contacts
Primary ContactJingyuan Fang, MD, PhD
Backup ContactDanfeng Sun, PhD
Outcome results
None listed