Modulating gut bacteria with antibiotics for rectal cancer treatment

Phase II Trial for Intestinal Microbiome Modulation With Antibiotics in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

This study is testing if using an antibiotic to change gut bacteria can help people with advanced rectal cancer respond better to radiation treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AC Camargo Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (São Paulo, São Paulo)
• Trial ID: NCT06793137 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial aims to enhance the treatment response in patients with locally advanced rectal adenocarcinoma by using metronidazole to modulate the intestinal microbiome during neoadjuvant radiotherapy. Participants will receive a daily dose of 1,500 mg of metronidazole for the first seven days of treatment, with adherence monitored through patient records and consultations. The study will evaluate the effectiveness of this intervention by comparing outcomes to historical controls, focusing on the rate of complete pathological response and changes in the intestinal bacterial profile. Adverse effects will be closely monitored to ensure patient safety.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with locally advanced middle or lower rectal adenocarcinoma eligible for neoadjuvant treatment.

Not a fit: Patients with histologies other than adenocarcinoma or those with microsatellite instability phenotype adenocarcinomas may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and increase the rate of complete responses in rectal cancer patients.

How similar studies have performed: While this specific approach is novel, studies on the impact of gut microbiota modulation in cancer treatment have shown promising results.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Where this trial is running

São Paulo, São Paulo

• A.C Camargo Cancer Center — São Paulo, São Paulo, Brazil (Recruiting)

Study contacts

• Principal investigator: Samuel Aguiar Jr, MD, PhD — A.C. Camargo Cancer Center
• Study coordinator: Samuel Aguiar Jr, MD, PhD

Conditions Rectal Cancer, Adenocarcinoma; Total Neoadjuvant Therapy; Intestinal microbiota; Locally advanced rectal cancer