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Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer

Primary Purpose

Colorectal Cancer Stage II, Colorectal Cancer Stage III

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Metronidazole Oral Tablet
Placebo oral tablet
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer Stage II focused on measuring Metronidazole, Gut Microbiota, Postoperative Chemotherapy, Colorectal Cancer, Fusobacterium nucleatum

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • 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 HealthRecruiting
  • Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
  • Fudan University Shanghai Cancer Center
  • Zhongshan Hospital affiliated to Fudan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Metronidazole

Placebo

Arm 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).

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).

Outcomes

Primary Outcome Measures

Disease Free Survival, DFS
The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.

Secondary Outcome Measures

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

Full Information

First Posted
February 8, 2020
Last Updated
November 23, 2020
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Municipal Commission of Health and Family Planning, Ruijin Hospital, Fudan University, Shanghai Zhongshan Hospital, Shanghai Shenkang Hospital Development Center
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1. Study Identification

Unique Protocol Identification Number
NCT04264676
Brief Title
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

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2020 (Actual)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Municipal Commission of Health and Family Planning, Ruijin Hospital, Fudan University, Shanghai Zhongshan Hospital, Shanghai Shenkang Hospital Development Center

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Stage II, Colorectal Cancer Stage III
Keywords
Metronidazole, Gut Microbiota, Postoperative Chemotherapy, Colorectal Cancer, Fusobacterium nucleatum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
294 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metronidazole
Arm Type
Active Comparator
Arm 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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Metronidazole Oral Tablet
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Disease Free Survival, DFS
Description
The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall Survival, OS
Description
The time from the initial surgical treatment of colorectal cancer to death from any cause.
Time Frame
5 years
Title
Recurrence Rate, RR
Description
Percentage of patients who has recurrence during or after chemotherapy with Metronidazole or Placebo.
Time Frame
3 years, 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jingyuan Fang, MD, PhD
Phone
86-021-58752345
Email
jingyuanfang@sjtu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Danfeng Sun, PhD
Phone
86-021-58752345
Email
danfolsdf@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jingyuan Fang, MD, PhD
Organizational Affiliation
Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
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
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing-Yuan Fang, MD. Ph D.
First Name & Middle Initial & Last Name & Degree
Jing-Yuan Fang, MD. Ph D.
Facility Name
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Shi, MD. Ph D.
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanjun Cai, MD. Ph D.
Facility Name
Zhongshan Hospital affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianyong Sun, MD. Ph D.

12. IPD Sharing Statement

Learn more about this trial

Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer

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