Colon cancer in track 1. Colon adenoma in track 2. MedDRA version: 20.0 Level: PT Classification code 10009944 Term: Colon cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10048832 Term: Colon adenoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: metronidazole “B. Braun”
Product Name: Metronidazole
Pharmaceutical Form: Solution for injection
INN or Proposed INN: METRONIDAZOLE
Other descriptive name: Metronidazole
Concentration unit
Sponsors
Zealand University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male and female patients above 18 years of age with either: • right-sided colon cancer tumor with adenocarcinoma histologically verified scheduled for open or laparoscopic resection at the Department of Surgery, Herlev Hospital or Zealand University Hospital (track 1) • right-sided adenomas =2cm in diameter endoscopically verified scheduled for endoscopic mucosal resection at the Department of Surgery, Herlev Hospital or Zealand University Hospital (track 2a) Written informed consent must be obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: • Patients with previous allergic reaction to fosfomycin and/or metronidazole • Patients under current antibiotic treatment or patient who had the last dose of antibiotics 30 days prior to inclusion • Patients with a non-passable tumor or patients where a part of the tumor is not visible during endoscopy (Track 1) • Patients with neoadjuvant chemotherapy or radiation 12 months prior to the resection • Patients with a history of familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC) • Patients with a history of inflammatory bowel disease (IBD) • Patients under current treatment with warfarin (Marevan) and phenprocoumon (Marcoumar), or NOAK such as dabigatran (Pradaxa®), rivaroxiban (Xarelto®), edoxaban (Lixiana®) or apixaban (Eliquis®) • Patients under current treatment with Fenemal (Phenobarbital) • Patients who previously have received a fecal transplantation • Patients who have previously had colorectal cancer, and are now presenting with a secondary colon tumor • Patients with a current alcohol use disorder (AUD): defined as a patient who are currently drinking 8 or more drinks/week for women and 15 or more drinks/week for men • Predictable poor compliance (psychiatric disease, not speaking fluent Danish, mentally impaired etc) • Patients with an American Society of Anaesthesiologists physical status Classification (ASA score) of IV • Patients unable to be sedated • Pregnancy or lactation (fertile women must have a negative serum or urine pregnancy test to participate) • Fertile women who do not use safe contraception during the study period Following contraceptive methods are acceptable when used consistently and in accordance with both the product label and the instructions of the physician are: - Oral contraceptive, either combined or progestogen alone - Injectable progestogen - Implants of levonorgestrel - Estrogenic vaginal ring - Percutaneous contraceptive patches - Intrauterine device or intrauterine system with a documented failure rate < 1% per year - Male partner sterilization (vasectomy with documented azoospermia) prior to female patient´s entry into the study, and this male is the sole partner for that patient - Double barrier method: condom with spermicidal agent (foam/gel/film/cream/suppository), condom and occlusive cap (diaphragm or cervical/vault cap) with vaginal spermicidal agent (foam/gel/film/cream/suppository)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: • Safety assessment of the spraying of the right hemicolon with fosfomycin/metronidazol gel.;Primary end point(s): The primary outcome • A quantitative change in the bacterial biomass adherent to the colonic epithelium of the resected colon adjusted for baseline level found before the intervention through fluorescence in situ (FISH) technique. The specific measurement variable is biofilm depth and 2D and 3D biofilm mass. The method of aggregation will be means. The exploratory primary outcomes • The determination of differences in translational markers present in the resected tumor tissue adjusted for the level seen at the baseline (the therapeutic colonoscopy) through a principal component analysis (PCA). The translational markers of interest are tumor markers, and markers of the microenvironment and the immune response. The analyses will be performed using the PanCancer IO 360TM Gene Expression Panel (nanoString). • The determination of a change in the bacterial composition adjusted for the bacteria found at baseline before the intervention through fluorescence in situ (FISH) technique and sequencing with Metagenome.;Timepoint(s) of evaluation of this end point: Primary outcome A report with results from the biofilm depth analyses will be delivered when all samples have been analyzed. Exploratory primary outcome The results of the gene expression analysis of 770 genes will be delivered in a report. A report with results from the biofilm analyses will be delivered when all samples have been analyzed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Track 1: colon cancer • Differences in the presence of known bacterial drivers such as Fusobacterium nucleatum, Enterococcus faecalis, Bacteroides Fragilis, Escherischia coli, and Porphyromonas in the tumor samples from preoperative biopsies and the resected colon. • Differences in gene expression in the normal mucosa from preoperative biopsies and the resected colon using the PanCancer IO 360TM Gene Expression Panel (nanoString). • Differences in gene expression in the preoperative and operative blood samples determined by the nCounter® PanCancer Immune Profiling Panel (nanoString). • The pathological assessment of tumor: tumor type, grade of dysplasia, TNVM-stage, MSI-status along with an assessment of the immunological response using the Immunoscore and an assessment of the biofilm present on the tumor. • The pathological assessment of the normal mucosa of the right hemicolon: presence of biofilm, dysplasia and inflammation. • Safety assessment of the spraying of the right hemicolon with fosfomycin/metronidazole gel. This will be assessed through adverse events at least 19 days after the intervention (postoperative day 14). Track 2: colon adenoma • Differences in gene expression in the normal mucosa from preoperative biopsies and the operative biopsies using the PanCancer IO 360TM Gene Expression Panel (nanoString). • Differences in gene expression in the tumor tissue from the mucosal resection compared with archived FFPE tumor tissue from patients with colon adenoma using the PanCancer IO 360TM Gene Expression Panel (nanoString). • Differences in gene expression in the preoperative blood samples and the blood samples taken on the operation day using the nCounter® PanCancer Immune Profiling Panel (nanoString). • The pathological assessment of polyp: type and size, along with an assessment of the immunological response and an assessment of the biofilm present on the polyp. • The pathological assessment of the normal mucosa of the right he | — |
Countries
Denmark
Contacts
Public ContactZealand University Hospital
Zealand University Hospital
Outcome results
None listed