Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer

Colorectal Cancer Stage III Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04264676
• Other study ID #: KY2019-066
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2020
• Est. completion date: March 2025

Study information

• Verified date: November 2020
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: Jingyuan Fang, MD, PhD
• Phone: 86-021-58752345
• Email: jingyuanfang[@]sjtu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 294
• Est. completion date: March 2025
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer Stage II
• Colorectal Cancer Stage III
• Colorectal Neoplasms

Intervention

Drug:
• Metronidazole 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.
• Placebo 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.

Locations

Country	Name	City	State
China	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	Shanghai	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Zhongshan Hospital affiliated to Fudan University	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine	Fudan University, Ruijin Hospital, Shanghai Municipal Commission of Health and Family Planning, Shanghai Shenkang Hospital Development Center, Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival, DFS	The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.	5 years
Secondary	Overall Survival, OS	The time from the initial surgical treatment of colorectal cancer to death from any cause.	5 years
Secondary	Recurrence Rate, RR	Percentage of patients who has recurrence during or after chemotherapy with Metronidazole or Placebo.	3 years, 5 years