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Cola

Clostridium novyi-NT spores

Luis A Diaz, MD

This study will include a one time intravenous (IV) infusion of Clostridium novyi-NT (C. novyi-NT) spores to treat solid tumors which have not responded to standard therapy.

Investigators at the SKCCC have developed a bacterial strain (C. novyi-NT) that can infect tumors and destroy them, but does not grow in normal tissues. In animal experiments, a single intravenous injection of these bacteria can cause dramatic regression of many tumors, and the tumors do not recur in approximately (\~) 30% of the animals.

This is a phase I dose escalation study using a single dose of Clostridium novyi-NT spores in patients with treatment-refractory solid tumor malignancies. The overall objective of this study is to determine the safety and document any preliminary evidence of anti-tumor activity in this patient population.

One Time Injection of Bacteria to Treat Solid Tumors That Have Not Responded to Standard Therapy

Phase I Safety Study of Clostridium Novyi-NT Spores in Patients With Treatment-Refractory Solid Tumor Malignancies

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adenoma

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anti-Infective Agents

Metronidazole

Fosfomycin

Anti-Bacterial Agents

Antiprotozoal Agents

Antiparasitic Agents

14 patient with right-sided colon cancer receive intervention before the hemicolectomi.

both arms of this study use the same intervention.

14 patient with right-sided colon adenoma receive intervention before the endoscopic mucosa resection.

both arms of this study use the same intervention.

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.

therapeutic endoscopy with metronidazole and fosfomycin disodium

Astrid LB Bennedsen, M.D.

Ismail Gögenur, DMSc, MD,

Peter Vilmann, DMSc, MD

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.

The same intervention will apply to both arms of this study, the only difference is the patient group which receives the treatment.

In Clinical Trial, Track 1 and Track 2a will be registered as two different arms, but the results from each arm later on is going to be reported in separate publications.

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

Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma: a Clinical Proof-of-concept Intervention Study MEFO Trial

A quantitative change in the bacterial biofilm 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 in μm. The method of aggregation will be means.

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 mass in ng/cm\^2. The method of aggregation will be means.

- 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, 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.

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).

Assessment of the immunological response using immunoscore. A binary outcome of either high or low immunoscore

The pathological assessment of tumor: tumor type, grade of dysplasia, TNVM-stage, MSI- status.

A microbiological assessment of the biofilm present on the tumor in track 1. This will be reported as a binary outcome.

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 reported at least 19 days after the intervention (postoperative day 14).

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 using the Paris Classification and the Lateral Spreading Tumor Classification to determine tumor type.

The pathological assessment of polyp: size

an assessment of the immunological response via immunoscore

The microbiological assessment of polyp: an assessment of the biofilm present on the polyp. This will be reported as a binary outcome.

Assessment of the spraying of the right hemicolon with fosfomycin/metronidazole gel. By collecting reported adverse events at least 19 days after the intervention (postoperative day 14).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
One Time Injection of Bacteria to Treat Solid Tumors That Have Not Responded to Standard Therapy	NCT00358397	Tumors	Clostridium nov...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Preoperative Endoscopic Treatment With Fosfomycin and Metronidazole in Patients With Right-sided Colon Cancer and Colon Adenoma (MEFO-trial)	NCT04312360	Right-sided Col... Right-sided Col...	therapeutic end...	18 Years -	Zealand University Hospital

Spots Global Cancer Trial Database for bacteria

Every month we try and update this database with for bacteria cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bacteria

Every month we try and update this database with for bacteria cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bacteria cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.