To learn if adding metronidazole to standard therapy can decrease populations of Fusobacterium nucleatum (F. nucleatum) and other anaerobes (small organisms that cause infections) in participants with rectal cancer receiving neoadjuvant therapy, compared to neoadjuvant therapy alone.
Participants with locally advanced rectal cancers (T3, T4, or N+ disease) with decision to treat with total neoadjuvant therapy.
No previous cycles of cytotoxic chemotherapy in management of the index tumor.
Age ≥18 years. Because of dosing differences between pediatric and adult populations and the introduced variability with these regiments to the study's primary outcomes, participants <18 years of age, children are excluded from this study.
ECOG performance status ≤2 (Karnofsky ≥60%,)
Participants who have had chemotherapy or radiotherapy within 1 year prior to entering the study.
Participants who are receiving any other investigational agents.
Participants with brain metastases or other unresectable metastases who would therefore not undergo standard of care proctectomy.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to metronidazole or other agents used in study.