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 .
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.
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).
Single group
Metronidazole
DrugThis 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.
Complete clinical response in total neoadjuvant treatment of rectal adenocarcinoma
Absence of residual disease detectable by clinical examination, rectal endoscopy, nuclear magnetic resonance imaging.
Evaluate changes in the intestinal bacteria profile.
Intestinal analysis (RNA-16S analysis) on fecal samples before and after treatment.
Organ preservation rate.
Organ preservation rate after neoadjuvant treatment.
Complete pathological response rate among operated patients
Complete pathological response (pCR) in surgical pathological examination result.
Toxicity of neoadjuvant treatment.
Evaluation of neoadjuvant treatment toxicity using CTCAE 5.0.
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AC Camargo Cancer Center
Lead sponsor
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Collaborator
