Intestinal Microbiome Modulation With Antibiotics in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

NCT06793137 | Recruiting Phase 2

• 1 other identifier: CEP3589/24
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer is the second most common malignancy worldwide and one-third of these tumors are located in the rectum. The treatment may involve up to three modalities: radiotherapy, chemotherapy, and surgery. For several years, thanks mainly to Brazilian researchers, subgroups of patients have been selected for non-surgical treatment when chemoradiotherapy induces a complete clinical response. These treatment regimens have reached a plateau leading researchers to seek strategies that can increase response rates. Intestinal microbiota studies have shown that an overpopulation of certain anaerobic bacteria is generally associated with poorer treatment response. No study has attempted to intervene in the gut microbiota to increase the complete response rate in rectal cancer. The proposal of the investigators aims to modulate the intestinal microbiota through a phase 2 clinical trial, with the use of metronidazole as the intervention .

Conditions

Rectal Cancer, Adenocarcinoma

Keywords

Total Neoadjuvant Therapy; Intestinal microbiota; Locally advanced rectal cancer

Outcome Measures

Primary Outcomes (1)

• Complete clinical response in total neoadjuvant treatment of rectal adenocarcinoma

  Absence of residual disease detectable by clinical examination, rectal endoscopy, nuclear magnetic resonance imaging.

  Between 7 -10 days after TNT consolidation and 10 - 12 weeks after TNT induction

Secondary Outcomes (5)

• Evaluate changes in the intestinal bacteria profile.

  Up to 7 days before starting intervention with metronidazole and up to 7 days after the end of intervention with metronidazole.

• Organ preservation rate.

  6 to 12 weeks after the end of treatment.

• Complete pathological response rate among operated patients

  10 days after surgery.

• Toxicity of neoadjuvant treatment.

  Through treatment completion, an average of 6 months.

• Locoregional recurrence-free survival.

  3 years after the end of treatment.

Study Arms (1)

Antibiotic in neoadjuvant treatment of locally advanced rectal adenocarcinoma

EXPERIMENTAL

This study investigates the administration of an oral antibiotic, metronidazole, during the first seven days of radiotherapy for patients with locally advanced rectal adenocarcinoma undergoing total neoadjuvant treatment. Metronidazole is a safe medication with a very low risk of adverse effects and is commonly used to treat infections caused by anaerobic bacteria present in the intestinal microbiota. Additionally, certain genera of anaerobic bacteria are known to be associated with a poorer response to treatment.

Drug: Metronidazole

Interventions

Metronidazole DRUG

This intervention involves administering the oral antibiotic metronidazole during the first seven days of radiotherapy for patients with locally advanced rectal adenocarcinoma who are undergoing total neoadjuvant treatment. Metronidazole is considered a safe medication, with a very low risk of adverse effects. It is commonly used to treat infections caused by anaerobic bacteria that are part of the intestinal microbiota. Additionally, it is well established that certain genera of anaerobic bacteria are linked to a poorer response to treatment.

Antibiotic in neoadjuvant treatment of locally advanced rectal adenocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18 years old with middle and lower rectal adenocarcinoma, classified as locally advanced or where the tumor´s location necessitates rectal amputation surgery;
• Tumors located below the peritoneal reflection, as determined by MRI, will be defined as middle and lower rectum;
• Patients eligible for rectal amputation will be those with tumor whose distal margin is less than 2,0cm from the pectineal line, as determined by rectoscopy, or less than 2,0cm from the anorectal ring by palpation or MRI.
• Patients with middle rectum cancer candidates for radiotherapy as part of neoadjuvant treatment will be included according to the following criteria: mesorectal fascia compromised by direct extension of the primary tumor or by an affected lymph node; cT4 tumors.

You may not qualify if:

• Patients without performance status for total neoadjuvant treatment;
• Histologies other than adenocarcinoma;
• Adenocarcinomas with a microsatellite instability phenotype, as determined by immunohistochemistry;
• Patients with middle rectal tumors who are not indicated for radiotherapy in the neoadjuvant treatment regimen, according to the institutional protocol (tumors cT3N0, with free mesorectal fascia; cT1-3 N+, with free mesorectal fascia).

Sponsors & Collaborators

• AC Camargo Cancer Center: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (1)

A.C Camargo Cancer Center

São Paulo, São Paulo, 01509-010, Brazil

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Samuel Aguiar Jr, MD, PhD

  A.C. Camargo Cancer Center

  PRINCIPAL INVESTIGATOR

• Virgilio S Silva, MD, PhD

  A.C. Camargo Cancer Center

  STUDY CHAIR

• Renata T Mayumi, MD

  A.C. Camargo Cancer Center

  STUDY CHAIR

• Bruna E Catin Kupper, BSN, PhD

  A.C. Camargo Cancer Center

  STUDY CHAIR

Central Study Contacts

Samuel Aguiar Jr, MD, PhD

CONTACT

+ 55 (11) 2189-5010; samuel.aguiar@accamargo.org.br

Virgilio S Silva, MD, PhD

CONTACT

+ 55 (11) 2189-5010; virgilio.silva@accamargo.org.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, chief of colorectal cancer division at Hospital AC Camargo Cancer Center

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 27, 2025
• Study Start: July 22, 2024
• Primary Completion: October 31, 2025
• Study Completion: April 30, 2026
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)