JOURNAL ONKOLOGIE – STUDIE

Metronidazole as Preoperative Therapy in CRC / FusoMetro-001

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05748145

Studienbeginn:
September 2023

Letztes Update:
19.04.2024

Wirkstoff:
Metronidazole Oral

Indikation (Clinical Trials):
Colorectal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Oncology Institute of Southern Switzerland

Collaborator:
-

Kontakt

Sara De Dosso, MD
Kontakt:
Phone: +41 91 811 93 02
E-Mail: sara.dedosso@eoc.ch» Kontaktdaten anzeigen

Luigi Tortola, PhD
Kontakt:
Phone: +41 91 811 96 68
E-Mail: luigi.tortola@eoc.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Oncology Institute of Southern Switzerland
6500 Bellinzona
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Sara De Dosso, MD
Phone: +41 91 811 93 02
E-Mail: sara.dedosso@eoc.ch

Luigi Tortola, PhD
Phone: +41 91 811 96 68
E-Mail: luigi.tortola@eoc.ch» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Colorectal cancer (CRC) is among the most frequent tumor types and is a leading cause of

cancer-related death worldwide. Surgery represents the first therapeutic option, whereas

advanced cases are usually treated by established chemotherapy protocols, yet with variable

response rates.

Mechanisms underlying unresponsiveness are still largely unclear. Recently, the gut

microbiota, consisting of trillions of microorganisms, which populate the gastrointestinal

tract, has also been implicated in chemo-resistance.

Defined bacterial species have been reported to be associated with CRC. In particular,

Fusobacterium nucleatum (F.n.), a commensal bacterium of the oral cavity, is enriched in CRC

tissues and its abundance appears to be associated with reduced patient survival.

In experimental models F.n. promotes CRC cell proliferation and reduces tumor responsiveness

to 5-fluorouracil (5-FU). Furthermore, it suppresses tumor infiltration by immune cells

associated with improved prognosis.

Administration of metronidazole effectively reduces F.n. load and overall tumor growth in

animal models.

However, its efficacy in reducing F.n. loads in human CRC has not been verified so far.

The proposed proof-of concept trial aims at determining the effectiveness of metronidazole in

decreasing the F.n. load in tissues and possibly on its detrimental effects on tumor cells

and tumor microenvironment.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Written informed consent according to ICH/GCP regulations before registration.

- Age ≥ 18 years old

- Untreated, primary colorectal adenocarcinoma (> 15 cm from the anal verge)

- Colonoscopy with endoscopic biopsy for disease confirmation and correlative studies.

- Candidates for surgical resection prior to administration of any therapy.

Exclusion Criteria:

- Insufficient material on the tissue biopsy to be left in the archives of the Cantonal

Institute of Pathology for further evaluations/analyses

- Known prior history of hypersensitivity to metronidazole or other nitroimidazole

derivatives

- Oral or parenteral antibiotic therapy within the six weeks prior to enrolment

- Emergency surgery (planned within less than 14 days), where no opportunity to

administer preoperative oral antibiotics exists

- Other malignant disease within 5 years prior to study enrollment, except basocellular

or squamous skin cancer and carcinoma in situ cervices uteri

- Any previous anticancer treatment prior resection

- Women who are pregnant or breast feeding

- Fertile women or men who do not use safe contraception during the study period

- Other clinically significant concomitant disease states (e.g., renal failure, hepatic

dysfunction, cardiovascular disease, etc.),

- Inability to consent and follow the procedures of the study e.g. due to language

problems, psychological disorders, dementia, etc. of the participant,

- Participation in another study with investigational drug within the 30 days preceding

and during the present study,

- Any other serious underlying medical, psychiatric, psychological, familial or

geographical condition, which in the judgment of the investigator may interfere with

the planned staging, treatment, affect patient compliance or place the patient at high

risk from treatment-related complications

Studien-Rationale

Primary outcome:

1. Impact of metronidazole on F.n. loads in CRC tissues. (Time Frame - 12 (+ 3) days after surgery):
F.n. load assessed by qRT-PCR analysis in excised tumor tissues upon antibiotic treatment, as compared to corresponding diagnostic biopsies prior to treatment.

Secondary outcome:

1. Potential effects of metronidazole on the expression of immune cell markers in CRC tissue samples (Time Frame - 12 (+ 3) days after surgery):
Expression of multiple immune cell markers will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.

2. Potential effects of metronidazole on the expression of autophagy markers in CRC tissue samples (Time Frame - 12 (+ 3) days after surgery):
Expression of multiple autophagy signaling elements will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.

3. Potential effects of metronidazole on microbiome (Time Frame - 12 (+ 3) days after surgery):
Differences in community diversity and/or abundance of specific bacterial taxa between the tumor-associated microbiome prior to or after antibiotic treatment.

4. Potential effects of metronidazole on the intestinal metabolic profile (Time Frame - 12 (+ 3) days after surgery):
Measurement of changes in the biosynthesis pathways of intestinal bacteria by comparing the gut metabolic profile before and after antibiotic treatment. Fold changes in the abundance of bacterial metabolites will be evaluated.

Geprüfte Regime

Metronidazole Oral:
Metronidazole will be administered per os at 500 mg x 3/day, for 10 days prior to surgery.

Quelle: ClinicalTrials.gov

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