Clinical trial NCT04264676: Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer Stage II
Colorectal Cancer Stage III
Keywords: Metronidazole
Gut Microbiota
Postoperative Chemotherapy
Colorectal Cancer
Fusobacterium nucleatum
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Municipal Commission of Health and Family Planning
name: Ruijin Hospital
name: Fudan University
name: Shanghai Zhongshan Hospital
name: Shanghai Shenkang Hospital Development Center
First posted: 2020-02-11
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease Free Survival, DFS
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival, OS
timeFrame: 5 years
measure: Recurrence Rate, RR
timeFrame: 3 years, 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Division of Gastroenterology and Hepatology, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Jingyuan Fang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: