Neoplasms

Digestive System Diseases

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Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

All Drugs and Chemicals

Metronidazole

Anti-Bacterial Agents

Antiprotozoal Agents

Antiparasitic Agents

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).

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.

Metronidazole 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.

Placebo oral tablet

Jingyuan Fang, MD, PhD

Danfeng Sun, PhD

Jing-Yuan Fang, MD. Ph D.

Yan Shi, MD. Ph D.

Sanjun Cai, MD. Ph D.

Jianyong Sun, MD. Ph D.

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.

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 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.

The time from the initial surgical treatment of colorectal cancer to the earliest evidence of recurrence.

The time from the initial surgical treatment of colorectal cancer to death from any cause.

Percentage of patients who has recurrence during or after chemotherapy with Metronidazole or Placebo.

Shanghai Municipal Commission of Health and Family Planning

Ruijin Hospital

Fudan University

Shanghai Zhongshan Hospital

Shanghai Shenkang Hospital Development Center

Shanghai Jiao Tong University School of Medicine

Director of Department of Gastroenterology

Symptoms and General Pathology

Disease Progression

Herbal and Botanical

Cola

Have confirmed colorectal cancer-free and Polyp-free colon using colonoscopy

Have benign or precancerous polyps, including tubulovillous or villous adenomas, using colonoscopy

Have confirmed TNM staging of colorectal cancer

The T refers to the size and extent of the main tumor. The main tumor is usually called the primary tumor.

The N refers to the number of nearby lymph nodes that have cancer. The M refers to whether the cancer has metastasized. This means that the cancer has spread from the primary tumor to other parts of the body.

Have confirmed TNM staging of colorectal cancer

Momchilo Vuyisich, PhD

This is an observational study with the goal to improve the robustness of the scientific evidence linking Fusobacterium nucleatum (Fn) and/or other microorganisms to colorectal cancer (CRC) onset and/or progression. This is an approximately three-year study. There are two phases to this study, including: 1) pilot phase, 2) full study. There are also five arms in this study including cancer-free, pre-cancerous, and Colorectal cancer stages (I-III). The pilot study will include the recruitment of 50 participants per group (i.e., total of 250 participants). The full study will have an additional 150 participants per group (total of 1,000 participants). This study will recruit using clinical sites in the United States.

There are 5 timepoints in this study. If the participants are found to be medically eligible through diagnosis and medical information, they will provide samples (including: saliva, blood, urine, stool and tumor biopsy) at each timepoint and during the study. They will also answer health and wellness questions during this study. Additional data collection, including medical data, biopsies and other biological samples might happen at interim timepoints in case of adenoma/cancer disease progression (recurrence, metastasis). The participant's healthcare provider will determine if additional biopsies are required as a part of the standard of care. If collected, additional samples will be sent for research purposes.

This is an exploratory, longitudinal study that will follow approximately 1,000 participants over 4-6 clinical sites nationwide over a period of 3-4 years and collect molecular and phenotype data to obtain insights into the microbiome and colorectal cancer. Each site will enroll approximately 166-250 participants in total. Those that are polyp/cancer free, pre-cancerous and confirmed primary diagnosis of colorectal cancer (stage I, II and III) will be recruited. Participants will be recruited in primary, secondary, and tertiary care centers, depending on the study inclusion/exclusion criteria.

Participants complete surveys and collect samples including (blood, urine, stool, and saliva) using at-home/in-clinic kits provided by Viome. Participants are also asked to provide tissue or tumor samples if collected by their healthcare provider during a standard of care biopsy procedure. Biopsy samples for this test will be collected by the clinical staff at each study site. Additional data collection, including medical data, biopsies and other biological samples might happen at interim timepoints in case of adenoma/cancer disease progression (recurrence, metastasis). Additionally, participants complete a survey sent on a quarterly basis.

There are 5 timepoints (TP) in this study including: Timepoint 1, Timepoint 2, Timepoint 3, Timepoint 4, and Timepoint 5.

TP1 includes the initial diagnosis where the stage of cancer is determined by imaging (colorectal cancer stages I, II, or III) or colonoscopy results (healthy and pre-cancerous). All participants provide urine, blood, saliva, stool and complete survey.

TP2 includes Post Standard of Care (SOC). For cancer participants, samples will be collected 45 +/- 15 days after all treatments have been completed (this includes chemotherapy, radiation therapy, immunotherapy, and/or surgery). Those that are healthy and pre-cancerous will provide their samples, 90 +/- 15 days after the colonoscopy. All participants provide urine, blood, saliva, stool and complete survey.

TP3, 4, and 5 occur 1, 2 and 3 years respectively after diagnosis (TP1) for cancer-free and precancerous groups and 1, 2 and 3 years respectively after standard of care therapy (TP2) for the cancer groups. All participants provide urine, blood, saliva, stool and complete survey.

Microbiome in Colorectal Cancer Onset and Progression

The Role of the Microbiome in Colorectal Cancer Onset and Progression

Determine Fn species and strains, more specifically the prevalence and relative activity, and the differential gene expression and key pathways. The Investigators will also look at Microbial co-occurrence/abundance with Fn and local tumor microenvironment and tumor marker/mutations and their association with microbiome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Oral Metronidazole on Postoperative Chemotherapy in Colorectal Cancer	NCT04264676	Colorectal Canc... Colorectal Canc...	Metronidazole O... Placebo oral ta...	18 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
Microbiome in Colorectal Cancer Onset and Progression	NCT05368688	Colorectal Canc... Tumor CRC GI Cancer Gastrointestina...		50 Years - 80 Years	Viome

Spots Global Cancer Trial Database for fusobacterium nucleatum