Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer

Shanghai Jiao Tong University School of Medicine

Status and phase: Enrolling; Phase 2

Conditions: Colorectal Cancer Stage III; Colorectal Cancer Stage II

Treatments: Drug: Placebo oral tablet; Drug: Metronidazole Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04264676

KY2019-066

Details and patient eligibility

About

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.

Full 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.

Enrollment: 294 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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294 participants in 2 patient groups, including a placebo group

Metronidazole

Active Comparator group

Description:

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).

Treatment:

Drug: Metronidazole Oral Tablet

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo oral tablet