Metronidazole as Preoperative Therapy in CRC / FusoMetro-001

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Impact of metronidazole on F.n. loads in CRC tissues. [Срок оценки: 12 (+ 3) days after surgery]

Вторичные конечные точки (4)

• Potential effects of metronidazole on the expression of immune cell markers in CRC tissue samples [Срок оценки: 12 (+ 3) days after surgery]
• Potential effects of metronidazole on the expression of autophagy markers in CRC tissue samples [Срок оценки: 12 (+ 3) days after surgery]
• Potential effects of metronidazole on microbiome [Срок оценки: 12 (+ 3) days after surgery]
• Potential effects of metronidazole on the intestinal metabolic profile [Срок оценки: 12 (+ 3) days after surgery]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Швейцария · 1 центр

• Oncology Institute of Southern Switzerland — Bellinzona

Идентификаторы

NCT: NCT05748145 · FusoMetro-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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