Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma (MEFO-trial)

Summary

Clinical studies have shown that patients with right-sided colon cancer have reduced progression-free and overall survival compared to patients with left-sided colon cancer. At the same time, patients with right-sided colon adenomas have a higher risk of developing interval cancers after endoscopic mucosal resection. Dysbiosis and known bacterial drivers play a significant role in the carcinogenesis of colorectal cancer, and may contribute to the growth of adenomas. Clinical studies have found biofilm formation and positive staining for Fusobacterium nucleatum (FN) in almost all right-sided colon cancers and adenomas. The composition of bacteria also in the normal mucosa in these two groups of patients has been found to be different from healthy controls.

Endoscopic preoperative antibiotic local treatment of the biofilm and tumors would theoretically result in decreased tumor mass, recovery of the mucosa, and a normalization of the immune response in the treated section of the colon. The oral administration of the antibiotic metronidazole in mice has shown to lower the tumor load (FN-positive xenograft tumors) and decrease in intratumoral abundance of the pro-carcinogenic bacteria, FN.

The aim of this study is to investigate the effect of local antibiotic treatment with fosfomycin and metronidazole on tumor characteristics and the colonic biofilm in patients with right-sided colon cancer or right-sided colon adenomas. This is a clinical proof-of-concept intervention study, and the investigators are to our knowledge the first group to look into local antibiotic treatment of biofilm in patients with colon cancer or colon adenoma. It is based on a non-randomized trial design with an open label single group assignment. There are two tracks depending on the pathology of the tumor: 1) patients with right-sided colon cancer; 2a) patients with right-sided colon adenoma. The intervention is a therapeutic endoscopy where the antibiotics fosfomycin and metronidazole are sprayed throughout the right colon section from caecum to the right colon flexure (100ml of gel contains 800mg of fosfomycin and 200mg of metronidazole). Patients will be included prospectively from the surgical department of Herlev University Hospital and Zealand University Hospital once having received oral and written information, followed by signing the consent. There will be a retrospective cohort of patients with colon adenoma from 2018 (track 2b). The investigators will retrieve the archived adenoma tissue as control tissue. In Clinical Trial, Track 1 and Track 2a will be registered as two different arms that use the same intervention, but the results from each arm later on is going to be reported in separate publications.

Conditions

• Right-sided Colon Cancer
• Right-sided Colon Adenoma

Interventions

DRUG

therapeutic endoscopy with metronidazole and fosfomycin disodium

therapeutic endoscopy where the two drugs: metronidazole and fosfomycin disodium are sprayed through out the right colon section (from caecum to right colon flexure). This intervention is going to be performed on patients in both track 1 and track 2a.

Sponsors & Collaborators

• Costerton Biofilm Center

  collaborator UNKNOWN

• Reponex Pharmaceuticals A/S

  collaborator INDUSTRY

• Region Zealand

  collaborator OTHER

• Zealand University Hospital

  lead OTHER

Principal Investigators

• Astrid LB Bennedsen, M.D. · Department of Surgery, Zealand University Hospital

• Ismail Gögenur, DMSc, MD, · Department of Surgery, Zealand University Hospital

• Peter Vilmann, DMSc, MD · Department of Surgery, Herlev Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-01-16

Primary Completion

2022-04-13

Completion

2023-07-01

Countries

• Denmark

Study Locations