Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Stage II; Colorectal Cancer Stage III
• Intervention / Treatment: Drug: Metronidazole Oral Tablet; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 294
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingyuan Fang, MD, PhD; Phone Number: 86-021-58752345; Email: jingyuanfang@sjtu.edu.cn
• Study Contact Backup: Name: Danfeng Sun, PhD; Phone Number: 86-021-58752345; Email: danfolsdf@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Not yet recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Sanjun Cai, MD. Ph D.
    • Shanghai, Shanghai, China, 200032
      • Not yet recruiting
      • Zhongshan Hospital Affiliated to Fudan University
      • Contact: Jianyong Sun, MD. Ph D.
    • Shanghai, Shanghai, China, 200001
      • Recruiting
      • 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
      • Principal Investigator: Jing-Yuan Fang, MD. Ph D.
      • Contact: Jing-Yuan Fang, MD. Ph D.
    • Shanghai, Shanghai, China, 200025
      • Not yet recruiting
      • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Yan Shi, MD. Ph D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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).	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 Comparator: 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).	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival, DFS	The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival, OS	The time from the initial surgical treatment of colorectal cancer to death from any cause.	5 years
Recurrence Rate, RR	Percentage of patients who has recurrence during or after chemotherapy with Metronidazole or Placebo.	3 years, 5 years

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Fudan University; Shanghai Zhongshan Hospital; Ruijin Hospital; Shanghai Municipal Commission of Health and Family Planning; Shanghai Shenkang Hospital Development Center
• Investigators: Principal Investigator: Jingyuan Fang, MD, PhD, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: February 8, 2020
• First Submitted That Met QC Criteria: February 8, 2020
• First Posted (Actual): February 11, 2020

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Metronidazole; Colorectal Cancer; Gut Microbiota; Postoperative Chemotherapy; Fusobacterium nucleatum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: KY2019-066

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No