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Metronidazole as Preoperative Therapy in CRC / FusoMetro-001

Primary Purpose

Colorectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Metronidazole Oral
Sponsored by
Oncology Institute of Southern Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Oncology Institute of Southern SwitzerlandRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metronidazole treated arm

Arm Description

Administration of Metronidazole for 10 days prior to surgery in CRC patients

Outcomes

Primary Outcome Measures

Impact of metronidazole on F.n. loads in CRC tissues.
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 Measures

Potential effects of metronidazole on the expression of immune cell markers in CRC tissue samples
Expression of multiple immune cell markers will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.
Potential effects of metronidazole on the expression of autophagy markers in CRC tissue samples
Expression of multiple autophagy signaling elements will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.
Potential effects of metronidazole on microbiome
Differences in community diversity and/or abundance of specific bacterial taxa between the tumor-associated microbiome prior to or after antibiotic treatment.
Potential effects of metronidazole on the intestinal metabolic profile
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.

Full Information

First Posted
January 26, 2023
Last Updated
October 20, 2023
Sponsor
Oncology Institute of Southern Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT05748145
Brief Title
Metronidazole as Preoperative Therapy in CRC / FusoMetro-001
Official Title
Preoperative Treatment With Metronidazole to Evaluate the Efficacy in Reducing Fusobacterium Nucleatum Tumor Colonization in Patients With Colorectal Cancer (CRC): a Proof-of-concept Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 11, 2023 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oncology Institute of Southern Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The proposed proof-of concept trial aims at determining the effectiveness of metronidazole in decreasing the Fusobacterium nucleatum load in tissues and possibly on its detrimental effects on tumor cells and tumor microenvironment.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Proof of concept
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metronidazole treated arm
Arm Type
Experimental
Arm Description
Administration of Metronidazole for 10 days prior to surgery in CRC patients
Intervention Type
Drug
Intervention Name(s)
Metronidazole Oral
Intervention Description
Metronidazole will be administered per os at 500 mg x 3/day, for 10 days prior to surgery.
Primary Outcome Measure Information:
Title
Impact of metronidazole on F.n. loads in CRC tissues.
Description
F.n. load assessed by qRT-PCR analysis in excised tumor tissues upon antibiotic treatment, as compared to corresponding diagnostic biopsies prior to treatment.
Time Frame
12 (+ 3) days after surgery
Secondary Outcome Measure Information:
Title
Potential effects of metronidazole on the expression of immune cell markers in CRC tissue samples
Description
Expression of multiple immune cell markers will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.
Time Frame
12 (+ 3) days after surgery
Title
Potential effects of metronidazole on the expression of autophagy markers in CRC tissue samples
Description
Expression of multiple autophagy signaling elements will be assessed in tissue samples by immunohistochemistry and immunofluorescence. Number of positive cells/mm2 will be evaluated.
Time Frame
12 (+ 3) days after surgery
Title
Potential effects of metronidazole on microbiome
Description
Differences in community diversity and/or abundance of specific bacterial taxa between the tumor-associated microbiome prior to or after antibiotic treatment.
Time Frame
12 (+ 3) days after surgery
Title
Potential effects of metronidazole on the intestinal metabolic profile
Description
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.
Time Frame
12 (+ 3) days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sara De Dosso, MD
Phone
+41 91 811 93 02
Email
sara.dedosso@eoc.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Luigi Tortola, PhD
Phone
+41 91 811 96 68
Email
luigi.tortola@eoc.ch
Facility Information:
Facility Name
Oncology Institute of Southern Switzerland
City
Bellinzona
State/Province
Ticino
ZIP/Postal Code
6500
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara De Dosso, MD
Phone
+41 91 811 93 02
Email
sara.dedosso@eoc.ch
First Name & Middle Initial & Last Name & Degree
Luigi Tortola, PhD
Phone
+41 91 811 96 68
Email
luigi.tortola@eoc.ch

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Metronidazole as Preoperative Therapy in CRC / FusoMetro-001

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